Diagnostics & Mitigation

As per the FDA, In vitro diagnostic (IVD) devices are tests performed on samples taken from the human body, such as swabs of mucus from inside the nose or back of the throat, or blood taken from a vein or fingerstick. IVDs can detect diseases or other conditions and can be used to monitor a person’s overall health to help cure, treat, or prevent diseases. There are several types of SARS-CoV-2 and COVID-19 related IVDs:

  • Diagnostic Tests – Tests that detect parts of the SARS-CoV-2 virus and can be used to diagnose infection with the SARS-CoV-2 virus. These include molecular tests and antigen tests.
  • Serology/Antibody Tests – Tests that detect antibodies (e.g., IgM, IgG) to the SARS-CoV-2 virus. Serology/antibody tests cannot be used to diagnose a current infection.
  • Tests for Management of COVID-19 Patients – Beyond tests that diagnose or detect SARS-CoV-2 virus or antibodies, there are also tests that are authorized for use in the management of patients with COVID-19, such as to detect biomarkers related to inflammation. Once patients are diagnosed with COVID-19 disease, these additional tests can be used to inform patient management decisions.

To date, the FDA has authorized 255 tests under EUAs; these include 204 molecular tests, 47 antibody tests, and 4 antigen tests.


  • Widely available SARS-CoV-2 IgG assays (Abott, DiaSorine, Roche, and Siemens) and a novel immunoassay (Oxford) all achieved at least 98% sensitivity and 98% specificity when evaluated with identical sample sets taken 30 days or more post-symptom onset [Link] (09/28/20)
  • A modified SARS-CoV-2 PCR testing procedure eliminates the bottleneck step of RNA extraction and achieves high sensitivity and specificity [Link] (09/28/20)
  • Multiplexed single molecule array (Simoa) assay for immunoglobulin isotypes against SARS-CoV-2 proteins enables early serological profiling in patients [Link] (09/21/20)
  • All-In-One dual CRISPR-Cas12a assay enables one-pot, ultrasensitive, and visual SARS-CoV-2 detection within 20 minutes [Link] (09/21/20)
  • CovidNudge, a portable 90-minute point-of-care real time RT-PCR test, is sensitive and specific [Link] (09/21/20)
  • A 3D printed biosensing platform detects antibodies within seconds using smartphone interface, and is refreshed for another test in one minute [Link] (09/15/20)
  • New PCR-based diagnostic method based on first single-stage combinatorial pooling can increase testing capacity up to a factor of ten and is cost effective [Link] (09/14/20)
  • Single Molecule Array (Simoa) SARS-CoV-2 antigen test detects plasma levels of Spike S1 subunit and can be used to identify active infection and monitor disease progression [Link] (09/10/20)
  • High agreement (100% positive agreement and 99.4% negative) observed between SARS-CoV-2 RT-PCR testing results between enhanced saliva specimens and nasopharyngeal swabs [Link] (09/07/20)
  • Test combining PCR and antibody tests at point-of-care increases detection and is not impacted by D614G mutation in virus [Link] (09/04/20)
  • New point-of-care RT-LAMP test can detect SARS-CoV-2 in under 40 minutes without requiring RNA extraction and comes with a disposable cartridge and smartphone reader [Link] (09/02/20)
  • Sample pooling only marginally improves testing capacities in high prevalence (>10%) settings [Link] (09/02/20)
  • Repeat testing for SARS-CoV-2 by RT-PCR shows low utility in study of over 1000 patients [Link] (09/01/20)

Select diagnostics kits/assays which have received approval are highlighted below

(*Order by diagnostics kits/assays name A ~ Z)

Product: Advanta Dx SARS-CoV-2 RT-PCR Assay

Date of approval: August 25, 2020 (FDA EUA)

Time: –

Brief Description: Extraction-free saliva-based RT-PCR test

Details: Advanta Dx SARS-CoV-2 RT-PCR Assay, an extraction-free saliva-based test to detect nucleic acid from the SARS‑CoV‑2 virus, designed to be run on the  Fluidigm Biomark HD microfluidics platform. As it is saliva-based, the Advanta Dx SARS-CoV-2 RT-PCR Assay does not require collection via invasive nasopharyngeal swab. The clinical study associated with the EUA submission demonstrated 100 percent agreement between the saliva results from the Advanta Dx SARS-CoV-2 RT-PCR Assay and the results from paired nasopharyngeal samples tested with authorized assays. The company’s microfluidics technology enables processing of more samples per batch than more traditional, microwell plate-based PCR technology. The Biomark HD platform can generate as many as 6,000 test results per day on a single system.

Source Link

Product: BinaxNOW COVID-19 Ag Card

Date of approval: August 26, 2020 (FDA EUA)

Time: 15 min

Brief Description: Ag Card is a rapid, reliable, highly portable, and affordable tool.

Details: Abbott’s BinaxNOW COVID-19 Ag Card is a rapid, reliable, highly portable, and affordable tool for detecting active coronavirus infections at massive scale. Test delivers results in just 15 minutes with no instrumentation, using proven lateral flow technology with demonstrated sensitivity of 97.1% and specificity of 98.5% in clinical study. Abbott will offer a no-charge complementary phone app, which allows people to display their BinaxNOW test results when asked by organizations where people gather, such as workplaces and schools. The company will ship tens of millions of tests in September, ramping to 50 million tests a month at the beginning of October.

Source Link

Product: SalivaDirect

Date of approval: August 15, 2020 (FDA EUA)

Time: Unknown

Brief Description: Saliva Sample Processing without separate nucleic acid extraction.

Details: Yale intends to provide SalivaDirect protocol to interested labs as opensource. SalivaDirect does not require any special type of swab or collection device; a saliva sample can be collected in any sterile container. This test is also unique because it does not require a separate nucleic acid extraction step. This is significant because the extraction kits used for this step in other tests have been prone to shortages in the past. Being able to perform a test without these kits enhances the capacity for increased testing, while reducing the strain on available resources. Additionally, the SalivaDirect methodology has been validated and authorized for use with different combinations of commonly used reagents and instruments, meaning the test could be used broadly in most high-complexity labs.

Source Link

Product: ID NOW COVID-19 assay

Date of approval: March 27, 2020 (FDA EUA)

Brief description: Rapid test targeting COVID-19 RdRp gene (PoC)

Time: Positive results may be detected in as little as 5 minutes and negative results in 13 minutes

Details: ID NOW COVID-19 assay performed on the ID NOW Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology intended for the qualitative detection of nucleic acid from the SARS-CoV-2 viral RNA in direct nasal, nasopharyngeal or throat swabs and nasal, nasopharyngeal or throat swabs eluted in viral transport media from individuals who are suspected of COVID-19 by their healthcare provider.

Source Link

Product: SARS-CoV-2 IgG assay

Date of approval: April 26, 2020 (EUA & CE Mark)

Time: Unknown

Brief Description: Detection of SARS-CoV-2 antibody

Details: The SARS-CoV-2 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum, serum separator tube and plasma (ACD, CPD, CPDA-1, dipotassium EDTA, tripotassium EDTA, lithium heparin, lithium heparin separator tube, sodium citrate, sodium heparin). The SARS-CoV-2 IgG assay is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The SARSCoV-2 IgG assay should not be used to diagnose acute SARS-CoV-2 infection. Testing is limited to laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform moderate or high complexity test.

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Product: Alinity m SARS-CoV-2 assay

Date of approval: May 11, 2020 (FDA EUA)

Time: Unknown

Brief Description: Real-time RT-PCR assay to be run on run on the Alinity m system

Details: The Alinity m SARS-CoV-2 assay is a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) test intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in nasal swabs, self-collected at a health care location or collected by a healthcare worker, nasopharyngeal (NP) and oropharyngeal (OP) swabs collected by a healthcare worker or bronchoalveolar lavage fluid (BAL) from patients suspected of COVID-19 by their healthcare provider. Testing is limited to laboratories certified under the CLIA, to perform moderate or high complexity tests.

Source Link

Product: RealTime SARS-C0V-2 assay

Date of approval: March 18, 2020 (EUA)

Details: The Abbott RealTime SARS-C0V-2 assay is an Emergency Use Authorization (EUA) test authorized by the U.S. FDA for use by authorized laboratories, using real-time (RT) polymerase chain reaction (PCR) technology for the qualitative detection of nucleic acids from the SARS-CoV-2 virus and diagnosis of SARS-CoV-2 virus infection from individuals meeting CDC clinical and/or epidemiological testing criteria.

Source Link

Product: LineaCOVID-19 Assay Kit

Date of approval: May 13, 2020 (FDA EUA)

Time: Unknown

Brief Description: RT-PCR based qualitative detection of SARS-CoV-2 RNA

Details: Applied DNA Sciences’ Linea COVID-19 SARS-CoV-2 assay kit is a real-time polymerase chain reaction (RT-PCR) test for the qualitative detection of SAR S-CoV-2 RNA in upper respiratory specimens. The Linea COVID-19 SARS-CoV-2 Assay Kit provides a high-throughput solution to help laboratories address the urgent need for patient testing during the Coronavirus pandemic.

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Product: iAMP COVID-19 Detection Kit

Date of approval: April 10, 2020 (EUA)

Time: 1.5 h sample to result.

Brief Description: Real-time reverse transcription isothermal amplification test

Details: The test is based on a proprietary isothermal amplification technology termed OMEGA amplification. OMEGA primer sets are designed to specifically detect RNA and later cDNA from the N and ORF-1ab genes of the SARS-CoV-2 virus in nasal, nasopharyngeal and/or oropharyngeal swabs from patients with signs and symptoms of infection who are suspected of COVID-19. The iAMP COVID-19 assay’s key differentiator from current rRT-PCR COVID-19 assays is its ability to detect SARS-CoV-2 RNA directly from samples without prior RNA extraction process.

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Product: BD Veritor System for Rapid Detection of SARS-CoV-2 (Rapid Antigen Testing)

Date of approval: July 06, 2020 (FDA EUA)

Time: 15 min

Brief Description: Rapid Point-of-Care Antigen Test

Details: FDA granted EUA for a rapid, point-of-care, SARS-CoV-2 diagnostic test for use with its broadly available BD Veritor Plus System. The launch of this new assay that delivers results in 15 minutes on an easy-to-use, highly portable instrument is critical for improving access to COVID-19 diagnostics because it enables real-time results and decision making while the patient is still onsite. BD will begin shipping the new test and expects to ramp-up manufacturing capacity to 2 million tests per week by the end of September.

Source Link

Product: Access SARS-CoV-2 IgG

Date of approval: June 26, 2020 (EUA and CE)

Time: Unknown

Brief Description: Antibodies to SARS-CoV-2 in serum

Details: Qualitative detection of IgG antibodies to SARS-CoV-2 in human serum, serum separator tubes, and plasma (lithium heparin, dipotassium EDTA, tripotassium EDTA, and sodium citrate). Intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

Source Link

Product: Real-Time Fluorescent RT-PCR Kit for Detecting SARS-2019-nCoV

Date of approval: April 24, 2020 (EUA)

Brief Description: Taqman RT-PCR for ORF1ab gene

Time: 4 h for 192 samples

Details: On April 24, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) amendment for BGI’s Real-Time Fluorescent RT-PCR Kit for Detecting SARS-CoV-2. The amendment expands the previously issued EUA label to further include the use of automated sample preparation system, additional viral RNA extraction kit and PCR systems for testing a broader range of clinical samples. Specifically, viral RNA extraction can be processed by the kits manufactured by MGI (a subsidiary of BGI Group) or Qiagen. In addition, the highly sensitive SARS-CoV-2 detection test can return results within 4 hours for 192 samples collected from throat (oropharyngeal) swabs, nasopharyngeal swabs, anterior nasal swabs, mid-turbinate nasal swabs, nasal washes, nasal aspirates and bronchoalveolar lavage fluid (BALF) using the MGI automated sample preparation system.

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Product: BioFire Respiratory Panel 2.1

Date of approval: May 1, 2020 (EUA)

Time: Unknown

Brief Description: Multiplex RT PCR for identification of several viruses including COVID-19

Details: BioFire Respiratory Panel 2.1 is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and differentiation of nucleic acids from multiple respiratory viral and bacterial organisms, including nucleic acid from the SARS-CoV-2 virus, in nasopharyngeal swabs (NPS) obtained from individuals suspected of COVID-19 by their healthcare provider.

Source Link

Product: 2019-nCoV IgG/IgM Antibody Detection Kit (Colloidal Gold)

Date of approval: April 6, 2020 (CE)

Brief Description: IgG/IgM Antibody Detection Kit

Time: 10 min.

Details: Simultaneous detection of SARS-CoV-2 specific IgM and IgG antibodies: The 2019-nCov IgG/IgM Rapid Test Device is a rapid chromatographic immunoassay for the qualitative detection of IgG & IgM antibody of Coronavirus in human venous whole blood, serum or plasma.

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Product: SARS-COV-2 R-GENE

Date of approval: May 6, 2020 (EUA)

Time: 4-5 h

Brief Description: Real-time PCR kit for the detection of SARS-COV-2

Details: The SARS-COV-2 R-GENE kit is a molecular detection kit, using real-time PCR after viral nucleic acids extraction. Assay includes all necessary reagents optimized to detect SARS-COV-2 for in vitro diagnostic use. Two triplex PCR for reliable diagnosis even if the virus mutates – PCR 1: SARS-COV-2 N gene (FAM) / Internal Control (HEX) / SARS-COV-2 RdRp gene (CY5) and PCR 2: SARBECOVIRUS E gene (FAM) / Internal Control (HEX) / Cellular Control (CY5)

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Product: Bio-Rad SARS-CoV-2 ddPCR Test & Platelia SARS-CoV-2 Total Ab assay

Date of approval: May 1, 2020 (EUA)

Time: Unknown

Brief Description: Quantitative Droplet Digital PCR & Qualitative detection of anti COVID-19 antibodies, based on immunoassay

Details:

Bio-Rad SARS-CoV-2 ddPCR Test: Qualitative detection of nucleic acid from SARS-CoV-2 innasopharyngeal, anterior nasal and mid-turbinate nasal swabspecimens as well as nasopharyngeal wash/aspirate and nasalaspirate specimens collected from individuals suspected of COVID-19 by their healthcare provider. Emergency use of thistest is limited to authorized laboratories.

Platelia SARS-CoV-2 Total Ab assay: Qualitative detection of total antibodies (including IgM/IgA/IgG) to SARS-CoV-2 in human serum and plasma (EDTA). Intendedfor use as an aid in identifying individuals with an adaptiveimmune response to SARS-CoV-2, indicating recent or priorinfection. Emergency use of this test is limited to authorizedlaboratories.

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Product: COVID-19 RT-PCR Peptide Nucleic Acid (PNA) kit

Date of approval: June 30, 2020 (EUA)

Time: Unknown

Brief Description: RT-qPCR PNA KIT

Details: The COVID-19 RT-qPCR PNA KIT is developed with reusable fluorescence hybridization probe real-time PCR technique using Peptide Nucleic Acid (PNA), sort of artificial nucleic acid which has more higher binding ability to its complement sequence DNA than which of DNA one, to in vitro reverse transcription of SARS-CoV-2 (also known as SARS-2019-nCoV) RNA followed with cDNA amplification and detection. The kit targets three specific genomic regions of SARS-CoV-2, those are RNA dependent RNA Polymerase (RdRP) gene , Nucleocapsid (N).

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Product: CRSP SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Assay

Date of approval: July 8, 2020 (FDA EUA)

Time: NA

Brief Description: RT-PCR based qualitative detection of SARS-CoV-2 RNA

Details: The CRSP SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Assay is a real-time RT-PCR test intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs collected from individuals who may have contracted the virus. Testing is limited to the Clinical Research Sequencing Platform at the Broad Institute which is certified under the CLIA, to perform high complexity tests.

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Product: qSARS-CoV-2 IgG/IgM Rapid Test

Date of approval: April 1, 2020 (EUA)

Brief Description: Lateral flow immunoassay for IgM and IgG antibodies

Time: 15 to 20 min.

Details: The Cellex qSARS-CoV-2 IgG/IgM Rapid Test is a lateral flow immunoassay intended for the qualitative detection and differentiation of IgM and IgG antibodies to SARS-CoV-2 in serum, plasma (EDTA, citrate) or venipuncture whole blood specimens from patients suspected of COVID-19 infection by a healthcare provider.

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Product: CDC Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay

Date of approval: July 02, 2020

Time: Unknown

Brief Description: RT-PCR based multiplex assay

Details: The CDC Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay is a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) test that detects and differentiates RNA from SARS-CoV-2, influenza A virus, and influenza B virus in upper or lower respiratory specimens. The assay provides a sensitive, nucleic-acid-based diagnostic tool for evaluation of specimens from patients in the acute phase of infection.

Source Link

Product: SARS-CoV-2 RT-PCR Test

Date of approval: July 01, 2020

Time: Unknown

Brief Description: RT-PCR based SARS-CoV-2 RNA detection kit

Details: CENTOGENE’S SARS-CoV-2 RT-PCR test is a real-time test based on the reverse transcription polymerase chain reaction (RT-PCR) for the qualitative detection of SARS-CoV-2, the underlying virus causing COVID-19. It is intended to be used with samples of the upper respiratory tract (oropharyngeal swabs) collected from individuals suspected by their healthcare provider to have COVID-19, belonging to a risk cohort, or having been in contact with a confirmed COVID-19 patient. The test is intended for use by qualified laboratory personnel to be performed in CENTOGENE’s CLIA certified high-complexity laboratories in Germany.

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Product: Xpert Xpress SARS-CoV-2 test

Brief Description: Rapid, near-patient RT-PCR test

Date of approval: March 20, 2020 (EUA)

Time: 30 min.

Details: Cepheid has developed an automated molecular test for the qualitative detection of SARS-CoV-2, the virus that causes COVID-19. The test leverages the design principles of our current Xpert Xpress Flu/RSV cartridge technology, in which multiple regions of the viral genome are targeted. The test can provide rapid detection of the current pandemic coronavirus SARS-CoV-2 in as soon as 30 minutes for positive results with less than a minute of hands on time to prepare the sample.

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Product: Logix Smart Coronavirus Disease 2019 (COVID-19) Kit

Date of approval: April 3, 2020 (EUA)

Brief Description: Single step real-time RT-PCR

Time: 63-90 min., depending on PCR equipment.

Details: The Logix Smart Coronavirus Disease 2019 (COVID-19) Test kit is an in vitro diagnostic test that uses our patented CoPrimer technology for the qualitative detection of the RNA from SARS-CoV-2 coronavirus (COVID-19). The test operates using a single step real-time reverse transcriptase polymerase chain reaction (RT-PCR) process in lower respiratory tract fluids (e.g. bronchoalveolar lavage, sputum, tracheal aspirate), and upper respiratory tract fluids (e.g. nasopharyngeal and oropharyngeal swabs) from patients who meet the clinical criteria. The test is available to laboratories certified under the CLIA.

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Product: LIAISON SARS-CoV-2 SOLUTIONS

Date of approval: April 24, 2020 (EUA)

Time: Unknown

Brief Description: SARS-CoV-2 IgM and SARS-CoV-2 S1/S2 IgG

Details: The testing solutions are based on two results from a single sample to determine both antibodies results. The selection of Spike protein antigens for both assays, recognized to be the most likely target of future COVID-19 vaccines and for IgG neutralizing antibodies. High sensitivity and specificity to ensure accurate results along the infection window. The use of IgG and IgM in combination can aid to shorten the diagnostic window improving the detection of seroconversion up to day 15 from PCR positivity.

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Product: Anti-SARS-CoV-2 ELISA (IgG)

Date of approval: May 4, 2020 (EUA, CE)

Time: Unknown

Brief Description: Anti-SARS-CoV-2 ELISA (IgG)

Details: ELISA test Qualitative detection of IgG antibodies against SARS-CoV-2 in human serum and plasma (K+-EDTA, Li+-heparin, Na+-citrate). Intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

Source Link

Product: EURORealTime SARS-CoV-2

Date of approval: June 8, 2020 (EUA, CE)

Time: Unknown

Brief Description: SARS-CoV-2 RT-PCR test

Details: Qualitative detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, nasopharyngeal, midturbinate and oropharyngeal swabs) and bronchioalveolar lavage (BAL) from individuals suspected of COVID-19 by their healthcare provider.

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Product: Illumina COVIDSeq Test

Date of approval: June 9, 2020

Time: 12 h

Brief Description: SARS-CoV-2 RT-PCR test

Details: The Illumina COVIDSeq Test is the first NGS test approved for use under the U.S. Food and Drug Administration’s Emergency Use Authorization (EUA). This amplicon-based NGS test includes 2019-nCoV primer and probe sets designed to detect RNA from the SARS-CoV-2 virus in nasopharyngeal, oropharyngeal, and mid-turbinate nasal swabs from patients with signs and symptoms of infection who are suspected of COVID-19.

Source Link

Product: SCoV-2 Detect IgM ELISA & SCoV-2 Detect IgG ELISA

Date of approval: June 30, 2020 (EUA) for IgM & June 10, 2020 (EUA) for IgG

Time: Unknown

Brief Description: ELISA that specifically detects IgM antibodies and IgG antibodies to SARS-CoV-2

Details:

The SCoV-2 Detect IgM ELISA is an in vitro diagnostic test for the qualitative detection of IgM antibodies to SARS-CoV-2 in human serum. The test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The SCoV-2 Detect IgM ELISA should be used to diagnose acute SARS-CoV-2 infection.
The SCoV-2 Detect IgG ELISA kit is an in vitro diagnostic test for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum. The test is intended as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The SCoV-2 Detect IgG ELISA should not be used to diagnose acute SARS-CoV-2 infection.

Source Link: IgM assay, IgG assay

Product: COVID-19 RT-PCR Test

Date of approval: July 24, 2020 (FDA EUA)

Time: Unknown

Brief Description: First Diagnostic Test for Screening of People Without Known or Suspected COVID-19 Infection; Allows pooled testing.

Details: U.S. Food and Drug Administration reissued the LabCorp COVID-19 RT-PCR Test emergency use authorization (EUA) to include two new indications for use: testing for people who do not have COVID-19 symptoms or who have no reason to suspect COVID-19 infection, and to allow pooled sample testing.

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Product: xMAP SARS-CoV-2 Multi-Antigen IgG Assay

Date of approval: July 16, 2020 (FDA EUA)

Time: Up to 96 samples per run in less than 3 h

Brief Description: SARS-CoV-2 antibody assay

Details: Detects IgG antibodies against 3 SARS-CoV-2 antigens, providing comprehensive results: S1 subunit of the spike protein, RBD of the spike protein, Nucleocapsid protein. It is designed for use with human serum and plasma samples, eliminating the need to implement additional collection protocols.

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Product: ARIES SARS-CoV-2 Assay

Date of approval: April 3, 2020 (EUA)

Time: Minimal hands-on time and an automated workflow delivers results in about 2 h

Brief Description: Exonuclease-sensitive probes for the ORF1ab and N viral genes provide superior specificity.

Details: This product is a qualitative test for the detection of SARS-CoV-2 nucleic acids in nasopharyngeal swab specimens from individuals suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is detectable in nasopharyngeal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.

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Product: NxTAG CoV Extended Panel Assay

Date of approval: March 27, 2020 (EUA)

Time: 96 samples in approximately 4 h.

Brief Details: SARS-CoV-2 detection using three viral genes (ORF1ab, E gene, and N gene)

Details: NxTAG CoV Extended Panel Assay for use on Luminex MAGPIX instrument is a RT-PCR test intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal swab specimens from individuals suspected of COVID-19 by their healthcare provider.

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Product: Accula SARS-Cov-2 Test

Brief Description: Rapid point-of-care PCR test

Date of approval: March 23, 2020 (FDA EUA)

Time: 30 min.

Details: Mesa Biotech has developed a qualitative, visually read test utilizing polymerase chain reaction (PCR) technology to detect SARS-CoV-2, the virus responsible for COVID-19. Using throat and nasal swabs, results are available in 30 minutes, based on the principles of Mesa’s commercially available Accula Influenza and RSV tests.

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Product: COVID-19 ELISA IgG Antibody Test

Date of approval: April 15, 2020 (EUA)

Brief Description: ELISA test IgG Antibody Test

Details: The COVID-19 ELISA IgG Antibody Test consists of two serial direct assays (ELISA) for the qualitative detection of human IgG antibodies in serum and plasma specimens collected from individuals suspected of prior infection with the virus that causes COVID-19 by their healthcare provider. An initial ELISA is performed against recombinant Receptor Binding Domain of SARS-CoV-2 in serum and plasma, followed for positive specimen by a confirmatory ELISA against full length SARS-CoV-2 Spike protein in serum and plasma. The COVID-19 ELISA IgG Antibody Test detects IgG antibodies as indicative of an immune response to SARS-CoV-2 in patients suspected of previous SARS-CoV-2 infection, or for the detection of IgG seroconversion in patients following known recent SARS-CoV-2 infection. The test is an aid in the diagnosis of patients with suspected of prior COVID-19 in conjunction with clinical presentation and the results of other laboratory tests. Results from the COVID-19 ELISA IgG Antibody Test should not be used as the sole basis for diagnosis and should not be used for the diagnosis of patients with acute COVID-19 infection. Testing is limited to the Mount Sinai Laboratory (MSL).

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Product: OPTI SARS-CoV-2 RT PCR Test

Date of approval: May 6, 2020

Time: Unknown

Brief Description: Real-time RT-PCR COVID-19 detection kit

Details: OPTI SARS-CoV-2 RT PCR Test is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens (such as nasal, nasopharyngeal, oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate) from patients suspected of COVID-19 by their health care provider. The SARSCoV-2 nucleic acid is generally detectable in upper and lower respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or coinfection with other viruses.

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Product: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Calibrators.

Date of approval: April 14, 2020 (EUA)

Time: Unknown

Brief Description: VITROS Anti-SARS-CoV-2 Total and IgG tests

Details: This test is one of the first high-throughput, automated COVID-19 antibody tests to be granted Emergency Use Authorization. Total antibody test detects all antibodies – IgM, IgA, and IgG and helps identify current or past exposure to SARS-CoV-2 whereas the IgG test detects the IgG antibody and helps identify an adaptive immune response.

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Product: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack

Date of approval: April 14, 2020

Time: 48 min

Details: The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack test when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is for the qualitative measurement of total antibody (including IgG and IgM) to SARS-CoV-2 in human serum and plasma (K2 EDTA) samples from patients suspected of COVID-19 by a healthcare provider, using VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack test is an aid in the diagnosis of patients with suspected SARS-CoV-2 infection in conjunction with clinical presentation and the results of other laboratory tests. Results from the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack test should not be used as the sole basis for diagnosis. Testing is limited to laboratories certified under the CLIA, to perform moderate and high complexity tests .

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Product: GeneFinder COVID-19 Plus RealAmp Kit

Date of approval: April 18, 2020 (FDA EUA, CE)

Brief Description: One step RT-PCR Kit

Time: 120 min

Details: GeneFinder COVID-19 Plus RealAmp Kit is the One-Step Reverse Transcription Real-Time PCR Kit designed to detect Novel Corona virus (COVID-19) qualitatively through Reverse Transcription reaction and Real-Time Polymerase Chain Reaction. It provides in about 120 minutes, detection for COIVD-19 in a single tube.

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Product: QIAstat-Dx Respiratory SARS-CoV-2 Panel

Date of approval: March 30, 2020 (EUA)

Time: Less than one minute for sample preparation and delivers results in about one hour.

Brief Description: A multiplexed nucleic acid real-time PCR test

Details: The QIAstat-Dx test kit can differentiate the SARS-CoV-2 coronavirus from 20 other respiratory infections in patients who may have similar symptoms in a single testing run of about one hour. It is a multiplexed nucleic acid test that evaluates samples such as nasopharyngeal swabs obtained from individuals suspected of respiratory tract infections. This new panel includes assays targeting two genes used to detect SARS-CoV-2, the pathogen behind the disease.

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Product: Quest SARS-CoV-2 rRT-PCR

Date of approval: July 18, 2020 (FDA EUA)

Time: Up to 96 samples per run in less than 3 h

Brief Description: The Quest test is the first COVID-19 diagnostic test to be authorized for use with pooled samples.

Details: This test is for the qualitative detection of nucleic acid from the SARS-CoV-2 in pooled samples containing up to four individual upper respiratory swab specimens (nasopharyngeal, mid-turbinate, anterior nares or oropharyngeal swabs) that are collected under observation using individual vials containing transport media from individuals suspected of COVID19 by their healthcare provider.

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Product: Sofia 2 SARS Antigen FIA

Date of approval: May 8, 2020

Time: 15 min

Brief Description: Lateral flow (strip) test for COVID-19 nucleocapsid protein

Details: Sofia 2 SARS Antigen FIA is a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 Instrument intended for the qualitative detection of the nucleocapsid protein antigen from SARSCoV-2 in nasopharyngeal (NP) and nasal (NS) swab specimens directly or after the swabs have been added to viral transport media from individuals who are suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleocapsid protein antigen is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleocapsid protein antigen, but clinical correlation with patient history and other diagnostic information is necessary to determine infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. Negative results should be treated as presumptive and confirmed with a molecular assay, if necessary for patient management.

Source Link

Product: Lyra Direct SARS-CoV-2 Assay

Date of approval: May 19, 2020

Time: Unknown

Brief Description: RT-PCR based SARS-CoV-2 RNA detection kit

Details: Lyra Direct SARS-CoV-2 Assay is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in nasal (NS), nasopharyngeal (NP), or oropharyngeal (OP) direct swab specimens from individuals suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is generally detectable in upper respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.

Source Link

Product: Elecsys Anti-SARS-CoV-2

Date of approval: May 2, 2020

Time: Unknown

Brief Description: Immunoassay to detect anti-COVID-19 antibodies

Details: Elecsys Anti-SARS-CoV-2 is a qualitative test for the detection of antibodies against SARS-CoV-2 in human serum or plasma (Heparin or EDTA). The product is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection

Source Link

Product: cobas SARS-CoV-2 test

Date of approval: March 12, 2020 (EUA), CE-IVD

Time: 96 results in about 3.5 h and a total of 384 results for the cobas 6800 System and 1056 results for the cobas 8800 System in 8 h.

Brief Description: RT-PCR for qualitative detection of SARS-CoV-2

Details: The tests are for use on the automated cobas 6800/8800 Systems under Emergency Use Authorization. Test is a single-well dual target assay, which includes both specific detection of SARS-CoV-2 and pan-sarbecovirus detection for the sarbecovirus subgenus family that includes SARS-CoV-2. The assay has a full-process negative control, positive control and internal control. Results are for the detection of SARS-CoV-2 RNA that are detectable in nasal, nasopharyngeal, and oropharyngeal swab samples during infection.

Source Link

Product: Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay

Date of approval: May 7, 2020

Time: Unknown

Brief Description: RT-PCR kit

Details: Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in in oropharyngeal (throat) swab, nasopharyngeal swab, anterior nasal swab, mid-turbinate nasal swab, and bronchoalveolar lavage (BAL) fluid from individuals suspected of COVID-19 by their healthcare provider.

Source Link

Product: Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing)

Date of approval: May 4, 2020 (EUA)

Time: Unknown

Brief Description: Real time RT-PCR using approved real-time PCR instrument

Details: Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in nasopharyngeal swabs, oropharyngeal (throat) swabs, anterior nasal swabs, mid-turbinate swabs, nasal washes, and nasal aspirates from individuals suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.

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Product: Allplex 2019-nCoV Assay

Date of approval: April 21, 2020 (EUA)

Time: 1 h 50 min

Brief Description: Multiplex real-time RT-PCR-based detection system

Details: Allplex test kit is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in human nasopharyngeal swab, oropharyngeal swab, anterior nasal swab, mid-turbinate and sputum specimens from individuals who are suspected of COVID-19 by their health care provider. Detection and identification of target genes (E gene, RdRP gene, N gene) specific for COVID-19 in a single tube.

Source Link

Product: Dimension Vista SARS-CoV-2 Total antibody assay (COV2T)

Date of approval: June 8, 2020 (EUA)

Time: Unknown

Brief Description: Total Antibody, CLIA

Details: The COV2T assay detects both IgM and longer-lasting IgG antibodies with high sensitivity of recent and prior infection. This allows for identification of patients who have developed an adaptive immune response, which indicates recent infection or prior exposure.

Source Link

Product: Sherlock CRISPR SARS-CoV-2 Kit

Date of approval: May 6, 2020

Time: Unknown

Brief Description: The assay is comprised of two steps. Step one is RT-LAMP where targeted SARS-CoV-2 genomic RNA is reverse transcribed to DNA then amplified by a strand-displacing DNA polymerase. Step two transcribes the amplified DNA to activate collateral cleavage activity of a CRISPR complex programmed to the target RNA sequence.

Details: Based on the SHERLOCK method, which stands for Specific High-sensitivity Enzymatic Reporter unLOCKing, the kit works by programming a CRISPR molecule to detect the presence of a specific genetic signature – in this case, the genetic signature for SARS-CoV-2 – in a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage (BAL) specimen. When the signature is found, the CRISPR enzyme is activated and releases a detectable signal. In addition to SHERLOCK, the company is also developing its INSPECTR platform to create an instrument-free, handheld test – similar to that of an at-home pregnancy test – that utilizes Sherlock Biosciences’ Synthetic Biology platform to provide rapid detection of a genetic match of the SARS-CoV-2 virus.

Source Link

Product: Stanford SARS-CoV-2 assay

Date of approval: April 8, 2020 (EUA)

Time: 2-3 days

Details: The Stanford Clinical Virology Laboratory was one of the first academic medical labs in the country to develop and administer a diagnostic test for the COVID-19 virus. Since starting to use the test in early March, more than 12,000 have been conducted on samples collected from people with symptoms of COVID-19 or with a known exposure to someone with the disease. Of these, about 9% have tested positive. The laboratory currently performs as many as 2,000 tests per day from samples collected at several Bay Area locations.

Source Link

Product: TaqPath COVID-19 Combo Kit.

Date of approval: March 13, 2020 (FDA EUA).

Brief Description: Multiplex real-time PCR detection of RNA from the SARS-CoV-2

Time: 94 patient specimens in under 3 hours.

Details: The TaqPath COVID-19 Combo Kit consists of both the TaqPath RT-PCR COVID-19 Kit and the TaqPath COVID-19 Control Kit. The kit can be used by clinical and public health laboratories to quickly evaluate up to 94 patient specimens in under 3 hours. The kit is approved for use with RNA extracted from nasopharyngeal swabs, nasopharyngeal aspirate (nasal aspirate), and bronchoalveolar lavage (BAL) from patients at risk of exposure to the SARS-CoV-2 virus or with signs and symptoms of COVID-19. Testing is limited to laboratories certified under the CLIA.

Source Link

Product: New York SARS-CoV Microsphere Immunoassay for Antibody Detection

Date of approval: April 30, 2020 (EUA)

Time: Unknown

Brief Description: Microsphere Immunoassay for Antibody Detection (IgG, IgM, IgA).

Details: Qualitative detection of total antibody (IgG, IgM, and IgA) to SARS-CoV-2 in human serum. Intended for use as an aid in identifying individuals who may have high levels of SARS-CoV-2-reactive antibodies in their blood that reflect an adaptive immune response to SARS-CoV-2 indicating recent or prior infection. Emergency use of this test is limited to Wadsworth Center, New York State Department of Health, which is certified under the CLIA to perform high complexity tests.

Source Link

Product: Quick SARS-CoV-2rRT-PCR Kit

Date of approval: May 7, 2020

Time: Unknown

Brief Description: RT-PCR COVID-19 detection kit

Details: Quick SARS-CoV-2rRT-PCR Kit is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, nasopharyngeal, mid-turbinate or oropharyngeal swabs), and lower respiratory specimens (such as sputum, tracheal aspirates, and bronchoalveolar lavage) from patients suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses

Source Link

Updated: 28 September, 2020.

Following is the list of all SARS-CoV-2 tests commercially available or in development for the diagnosis of COVID-19 collated by the Foundation for Innovative New Diagnostics (FIND), which is information directly submitted by test suppliers or obtained from publicly available sources.

An Overview of Coronavirus (COVID-19) Vaccines

Over the past 18 years, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now COVID-19 (SARS-CoV-2) have caused unimaginable distress, mortality, morbidity, social disturbances, and economic disruptions [1]. To mitigate the consequences of COVID-19 and to protect from future pandemics, vaccines are urgently needed. Since the pandemic started, scientists worldwide are evaluating different approaches at unprecedented speed with novel paradigms and accelerated development to trigger the immune system to produce effective neutralizing antibodies and enough T-cells that can fight COVID-19, in hopes of inducing the kind of responses that maybe associated with protection and minimal adverse events. As of August 19, 2020, there were 29 candidate vaccines in clinical testing and 138 candidate vaccines in preclinical evaluation as per the WHO‘s published draft vaccine landscape, which is continually updated.

Figure 1. An overview of different approaches to vaccine development. Image for illustration purpose only.

Fig. 1 shows at least eight different approaches that have been explored for the development of a vaccine. These include Whole virus vaccines (Weakened or Inactivated form), Viral-vector vaccines (Replicating or Non-replicating), Genetic forms (RNA, DNA), Protein-based vaccines (Subunit or Virus-like Particles). In addition, pre-existing vaccines (e. g. MMR, Poliovirus, or Tuberculosis) are being explored as well for the possibility that these might confer protection against the SARS-CoV-2 virus.

Vaccine Development Timelines

Steps and timelines for traditional and pandemic vaccine development are shown in Fig. 2. The traditional vaccine testing process begins with the Preclinical trials (in labs, and then in animals if it shows potential) followed by  the Phase I safety trials (20-100 healthy volunteers), the expanded Phase II trials (several hundred enrolled for observing common short-term side effects and dosing responses), and then Phase III efficacy trials (hundreds or thousands of volunteers). Vaccinated people are compared with people who have received a placebo or another vaccine so researchers can learn more about the test vaccine’s safety and effectiveness and identify common side effects.  Once a vaccine is successfully passed these requirements, the approval process is followed (CDC; FDA). A decade or longer is more typical for the completion of a successful candidate.

However, in a pandemic situation, a vaccine may receive Emergency Use Authorization (EUA) before getting any kind of formal approval, Phases II and III may be combined to shorten the time for development, and the Human challenge trials (controlled human infection model) can be skipped. The WHO Research Ethics Review Committee (ERC) was split over whether COVID-19 Human challenge trials should be performed in the absence of a rescue treatment. The current speed with which vaccines are being developed is remarkable, from the first deciphering of the SARS-CoV-2 genome published on 11 January 2020 through Phase III trials in 6 months, as compared with a typical timeline of 2 to 10 years. It should be noted that several companies have already pursued large scale manufacturing of vaccines before establishing the vaccine safety, efficacy and/or receiving the final regulatory approval.

Figure 2. Timelines for traditional and pandemic models of vaccine development.

As of August 19, 2020, there were 135+ vaccine programs in preclinical stages, and 19, 12, and 8 vaccines in Phase I, Phase II and Phase III, respectively, with two vaccines approved for limited use (CanSino vaccine for Military use only in China and the Russian Gamaleya Research Institute vaccine for Early use) (Source: Vaccine tracker).

Current Status

As of August 19, 2020, the global COVID-19 vaccine landscape included 167 vaccine candidates (Fig. 3); with 138 currently at exploratory or preclinical stages and 29 moving into clinical stages. Several advanced candidates have recently moved into clinical development, including mRNA-1273 from ModernaBNT162b1 from Pfizer, ChAdOx1 nCoV-19 from University of Oxford and AstraZeneca, Ad5-nCoV from CanSino Biologicals, and CoronaVac from Sinovac Biotech.

Figure 3. Pipeline of Vaccine candidates by technology platform and development stages (data source: WHO)

One example, the mRNA-1273 vaccine candidate manufactured by Moderna, is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized Spike (S) protein of SARS-CoV-2. The purpose of this design was to stimulate neutralizing antibodies directed at a portion of the S protein, which the virus uses to bind to human receptor and enter human cells [2]. Based on the results of the Phase 1 study, the 100 μg dose level was chosen as the optimal dose level to maximize the immune response while minimizing adverse reactions [2,3].  A large Phase III efficacy trial to evaluate a 100-μg dose began July 27. The final trial will enroll 30,000 healthy people at about 89 sites around the United States. On August 11, the government awarded the company an additional $1.5 billion in exchange for 100 million doses if the vaccine proves safe and effective.

All the leading five candidates (Table 1) were based on vaccines that contain viral particles like RNA that primed a better targeted immune response against a SARS-CoV-2 infection. According to Phase I/II results, these five candidates have illustrated (1) the ability to generate a substantial T-cell response against SARS-CoV-2 and (2) the ability to increase the levels of neutralizing antibodies that were effective in binding the S-protein of COVID-19 receptor binding domain [2-4,9,10].

Table 1. The characteristics of clinical-phase vaccine candidates (Updated July 24).

Features vs CandidatesModernaPfizerAstraZeneca/ Oxford Univ.CanSinoSinovac
Vaccine TypemRNA (mRNA-1273)mRNA (BNT162b1)Vector (ChAdOx1 nCoV-19)Vector (Ad5-nCoV)Inactivated + alum (CoronaVac; formerly PiCoVacc)
PhasePhase IICombined Phases II and IIIPhase IIIPhase IIIPhase III
No. of Doses22213
Dosage Conc.100 µg10 µg5 x 1010 viral particles5 x 1010 viral particles3 µg
Side EffectsMild to moderateMild to moderateMild to moderateMild to moderate; Grade 3 adverse effects were seen in 9%Mild to moderate
Neutralizing antibodyYesYesYesYesYes
Cellular ImmunityYesYesYesYesYes
Mfg. SupportCMOIn-houseCMOIn-HouseIn-House
Available byDec. 20Oct. 20Oct. 20Military use 
Warp speedYes (Phase III)YesYes
Phase III byJuly 27, 2020OngoingOngoingOngoingJuly 2020
Prior approvals  No RNA vaccines have been approved for human use.No RNA vaccines have been approved for human use.Similar vaccines have been approved by FDANo approved product of this kind to dateSimilar vaccines have been approved by FDA
Phase I/II results support large scale evaluation in Phase IIIYesYesYesYesYes
Clinical TrialsPhase III NCT04470427; Phase 2 NCT04405076; Phase 1 NCT04283461; Results in NEJM [2]Phase I/II 2020-001038-36; NCT04368728; Preprint results[3],[4]Phase III ISRCTN89951424; Phase IIb/III NCT04400838; Phase I/II PACTR2020069221651322020-001072-15; Results in Lancet [5]Phase I NCT04313127; Results in Lancet[6] Phase II NCT04341389; Results in Lancet [7]  Phase III NCT04456595; Phase I/II NCT04383574 ;NCT04352608; Results in Science [8]  

Repurposed (Pre-existing) Vaccines

Given the imperative for scale and speed, epidemiological investigations have suggested a strong correlation among countries with universal vaccination policies and the severity of COVID-19. Findings suggested that countries with universal vaccination policies against Bacillus Calmette-Guerin  (BCG, Tuberculosis) and/or against MMR (Measles, Mumps and Rubella) showed a significant reduction of mortality and infection rates [11-13]. Authors suggest that such pre-existing vaccines may boost an individual’s immune response, reduce the severity of COVID-19, and alleviate the symptoms associated with COVID-19. Multiple such studies have revealed interesting associations with COVID-19 severity and vaccination coverage in the population [13,14]. Despite the initiation of clinical trials (NCT04327206; NCT04357028), the WHO does not recommend such re-purposed vaccines until scientific evidence is provided. As cautioned by the WHO and while still in the middle of this pandemic, COVID-19 cases and deaths continue to increase over time in some BCG-using countries (e.g. Brazil, India, and Mexico) [Johns Hopkins, 15].

Finally, as the world awaits the vaccine as a salvation, strong coalition between developers, researchers, politicians, regulators, and funders will be needed to ensure that the approved vaccine candidate can be manufactured in large quantities and be supplied impartially to all impacted areas. Regular updates and details on promising vaccine candidates are outlined in our “Highlights” tab (Pandemic Response Dashboard).

Prepared by: Fuad Odeh & Sudheer Krishna. Updated : 19 August, 2020.

References

  1. COVID-19, SARS and MERS: are they closely related? Petrosilo et al. (2020), Clinical Microbiology and Infection: https://doi.org/10.1016/j.cmi.2020.03.026
  2. SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness, K. S. Corbett, bioRxiv (2020): https://doi.org/10.1101/2020.06.11.145920
  3. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report, Jackson et al., (2020) The New England Journal of Medicine (2020): DOI: 10.1056/NEJMoa2022483
  4. Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report, Mulligan et al., (2020) MedRxiv: https://doi.org/10.1101/2020.06.30.20142570
  5. Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine,  Sahin et al., (2020) MedRxiv: https://doi.org/10.1101/2020.07.17.20140533
  6. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial, Folegatti et al., (2020) The Lancet: https://doi.org/10.1016/S0140-6736(20)31604-4
  7. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomized, first-in-human trial, Zhu et al., (2020) The Lancet: https://doi.org/10.1016/S0140-6736(20)31208-3
  8. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial, Zhu et al., (2020) The Lancet: https://doi.org/10.1016/S0140-6736(20)31605-6
  9. Development of an inactivated vaccine candidate for SARS-CoV-2, Q. Gao et al., Science (2020): http://doi.org/10.1126/science.abc1932
  10. ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques, N.v. Doremalen, bioRxiv (2020): https://doi.org/10.1101/2020.05.13.093195
  11. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. Miller et al., MedRxiv (2020): https://doi.org/10.1101/2020.03.24.20042937
  12. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Escobar et al, (2020):  https://doi.org/10.1073/pnas.2008410117
  13. Considering BCG vaccination to reduce the impact of COVID-19, N. Curtis et al., The Lancet (2020): https://doi.org/10.1016/S0140-6736(20)31025-4
  14. Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19, R. Franklin et al., MedRxiv (2020): https://doi.org/10.1101/2020.04.10.20053207
  15. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices, Zwerling et al., (2011): PLoS Medicine: doi: 10.1371/journal.pmed.1001012
  • Janssen’s Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen (Ad26.COV2.S) induces potent humoral and cellular immune responses in mice [Link] (09/28/20)
  • Clover Biopharmaceuticals and GSK publish positive results for S-Trimer, a protein-based adjuvanted COVID-19 vaccine candidate, in nonhuman primates [Link] (09/28/20)
  • NVX-CoV2373, Novavax’ COVID-19 vaccine candidate, enters phase 3 study for 10,000 individuals in United Kingdom [Link] (09/28/20)
  • First participants dosed in Phase 3 ENSEMBLE trial evaluating safety and efficacy of Janssen’s COVID-19 vaccine candidate JNJ-78436735 (also known as Ad26.COV2.S) [Link] (09/28/20)
  • Reports suggest Sinovac’s CoronoVac vaccine was effective and showed no major adverse events in the 50,027 volunteers from China [Link] (09/28/20)
  • UK will host the world’s first Covid-19 human challenge trials, which will test deliberately infected healthy volunteers to assess the vaccines [Link] (09/28/20)
  • Inactivated SARS-CoV-2 vaccine CoronaVac from SinoVac approved for phase I/II trial in adolescents and children [Link] (09/28/20)
  • Optimized SARS-CoV-2 RBD or Spike antigens displayed on self-assembling protein nanoparticles can elicit potent immune responses [Link] (09/21/20)
  • Oxford University’s ChAdOx1 and Imperial’s saRNA vaccine platforms will also be tested in inhaled form [Link] (09/15/20)
  • First COVID-19 oral vaccine (tablet form) that can be stable at room temperature receives FDA Clearance of Investigational New Drug application [Link] (09/15/20)
  • A whole virion inactivated SARS-CoV-2 vaccine, BBV152 (Covaxin), demonstrates protective efficacy in a live viral challenge animal model [Link] (09/11/20)
  • BNT162b2, a nucleoside-modified messenger RNA (modRNA) candidate, fully protects the lungs of immunized rhesus macaques with strong T-cell responses [Link] (09/10/20)
  • Adenovirus based vaccine expressing full length, wild-type Spike antigen induces significantly high neutralizing antibodies when administered mucosally [Link] (09/10/20)
  • Investigational intranasal Ad26 vaccine candidate from BIDMC and Johnson & Johnson prevents severe clinical disease in animals following single immunization [Link] (09/04/20)
  • Spike-based priming leads to high neutralizing activity in mice and macaques [Link] (09/04/20)
  • Nanoparticle vaccine candidate NVX-CoV2373 elicits good antibody plus CD4+ T cell response and was generally safe in a phase 1/2 trial [Link] (09/04/20)
  • BCG vaccination reduces time to first COVID-19 infection as well as incidence of new infection in elderly patients [Link] (09/02/20)


Select promising vaccine candidates currently in clinical trials are detailed below.

Candidate: Protein subunit; NVX-CoV2373; Full-length recombinant SARS COV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M

Sponsors/Developers: Novavax, Inc.

Location: Australia; South Africa

Trial identifier: NCT04368988 (Phase 2); NCT04533399 (Phase 2)

Description: NVX-CoV2373 is a stable, prefusion protein made using Novavax’ proprietary nanoparticle technology. Novavax’ proprietary Matrix-M adjuvant will be incorporated with NVX-CoV2373 in order to enhance immune responses and stimulate high levels of neutralizing antibodies. NVX-CoV2373 was shown to be highly immunogenic in animal models measuring spike protein-specific antibodies, antibodies that block the binding of the spike protein to the receptor and wild-type virus neutralizing antibodies. High levels of spike protein-specific antibodies with ACE-2 human receptor binding domain blocking activity and SARS-CoV-2 wild-type virus neutralizing antibodies were observed after a single immunization. In addition, the already high microneutralization titers seen after one dose increased eight-fold with a second dose. High titer microneutralizing antibodies are generally accepted evidence that a vaccine is likely to be protective in humans.

On July 6, Novavax announced a U.S. government award of $1.6 billion to support clinical trials and manufacturing. If the trials succeed, Novavax expects to deliver 100 million doses for use in the United States by the first quarter of 2021. Plants in Europe and Asia would be able to satisfy more of the world’s demand. The agreement will fund the late-stage clinical studies necessary to determine the safety and efficacy of NVX-CoV2373, including a pivotal Phase 3 clinical trial with up to 30,000 subjects beginning in the fall of 2020.

On August 5, 2020, Novavax announced Phase 1 data from its Phase 1/2 randomized, observer-blinded, placebo-controlled trial of its COVID‑19 vaccine with and without Matrix‑M adjuvant in healthy adults 18-59 years of age. NVX‑CoV2373, the Company’s recombinant COVID-19 vaccine candidate adjuvanted with Matrix-M, was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera. NVX-CoV2373 induced neutralization titers in 100% of participants (5 ug adjuvanted dose group peak GMT: 3906) and the adjuvant induced robust polyfunctional CD4+ T cell responses. NVX-CoV2373 is stable and will allow handling in a liquid formulation that can be stored at 2 to 8 deg C, allowing for successful cold chain management with existing infrastructure.

Novavax announced on August 25, 2020, that the first volunteers have been enrolled to evaluate the immunogenicity and safety of NVX-CoV2373 candidate. The Phase 2 clinical trial expands on the age range of the Phase 1 portion by including older adults 60-84 years of age as approximately 50 percent of the trial’s population. The Phase 2 portion of the ongoing Phase 1/2 clinical trial is a randomized, placebo-controlled, observer-blinded study to evaluate the safety and immunogenicity of NVX-CoV2373 with Matrix-M in subjects aged 18 to 84 years. The clinical trial will assess two dose sizes (5 and 25 ug), each with 50 ug of Matrix‑M. Although the trial was designed to confirm immunogenicity and safety in adults, secondary objectives include preliminary evaluation of efficacy. The study is targeting enrollment of up to 1,500 healthy volunteers, with approximately 50 percent of participants ≥60 years of age, at up to 40 sites in the U.S. and Australia. The trial is supported by funding from the Coalition for Epidemic Preparedness Innovations (CEPI).

On September 02, 2020, the first publication of the Phase 1/2 Novavax nanoparticle SARS-CoV-2 vaccine program showed that candidate was safe (small participant number), with a good antibody and CD4+ T cell response (no CD8+ data provided). The trial is a randomized, placebo-controlled, phase 1-2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-ug and 25-ug doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype.

Status: Novavax has initiated its first Phase 3 study to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373, Novavax’ COVID-19 vaccine candidate. The trial is being conducted in the United Kingdom (UK), in partnership with the UK Government’s Vaccines Taskforce, and is expected to enroll and immunize up to 10,000 individuals between 18-84 (inclusive) years of age, with and without relevant comorbidities, over the next four to six weeks.

References:

  • Press Release: Novavax Announces $1.6 Billion Funding from Operation Warp Speed. Novavax (07/07/20).
  • Press Release: Novavax and FUJIFILM Diosynth Biotechnologies Initiate Large Scale Manufacturing of COVID-19 Vaccine Candidate. Novavax (07/23/20).
  • Press Release: Novavax Announces Positive Phase 1 Data for its COVID-19 Vaccine Candidate. Novavax (08/05/20).
  • Press Release: Novavax and Takeda Announce Collaboration for Novavax’ COVID19 Vaccine in Japan. Novavax (08/06/20).
  • Press Release: Novavax Initiates Efficacy Trial of COVID-19 Vaccine in South Africa. Novavax (08/17/20).
  • Press Release: Novavax Initiates Phase 2 Portion of Phase 1/2 Clinical Trial of COVID-19 Vaccine. Novavax (08/24/20).
  • Publication: Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. NEJM (09/02/20).
  • Press Release: Novavax Announces COVID-19 Vaccine Manufacturing Agreement with Serum Institute of India, Increasing Novavax’ Global Production Capacity to Over 2 Billion Doses Annually. Novavax (09/15/20).
  • Press Release: Novavax Initiates Phase 3 Efficacy Trial of COVID-19 Vaccine in the United Kingdom. Novavax (09/24/20).

Candidate: Adenovirus type 26 based vaccine JNJ-78436735, also known as Ad26.COV2.S

Sponsors/Developers: Johnson & Johnson, Beth Israel Deaconess Medical Center

Location: United States, Belgium, Brazil

Trial identifier: NCT04436276 (Phase1/2)

Description: Ad26 vector encoding for a membrane-bound stabilized S protein with a wild type signal peptide.

On June 10, Johnson & Johnson announced it was accelerating the timeline to start early-stage testing of Janssen’s vaccine candidate in humans in the second half of July.

The randomized, double-blind, placebo-controlled Phase 1/2a trial will see 1,045 people participating. Healthy participants in Belgium and the U.S. between the ages of 18 and 55, as well as those 65+, will be assigned to receive the vaccine candidate or a placebo. Johnson & Johnson has identified clinical study sites in cities that have underserved and underrepresented populations and is partnering with organizations to proactively identify and include diverse patient populations. Plans are also underway for a Phase 1 study in Japan, as well as a Phase 2 study in the Netherlands, Spain and Germany.

Janssen Plans to Produce More than 1 Billion Doses of a Potential Vaccine – Provided that the investigational vaccine proves to be safe and effective, the company aims to manufacture over 1 billion doses to be distributed globally through 2021. These efforts—along with research and development—are spurred by an expanded collaboration between Janssen and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health & Human Services.

Janssen is using the same technology that it has used in the development of its Ebola vaccine and investigational HIV, RSV and Zika vaccine candidates, which involves using an inactivated common cold virus that’s not replicating.

Johnson & Johnson on July 30, 2020, kicked off U.S. human safety trials for its COVID-19 vaccine after releasing details of a study in monkeys that showed its best-performing vaccine candidate offered strong protection in a single dose.

On August 20, 2020, Brazil’s regulator has approved a 6,000-participant phase 3 trial for Johnson & Johnson’s covid-19 vaccine. It is 6000 out of their planned 60000 international trial target.

Published results on September 03, 2020, indicate that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with this adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality.

Recent publication in Nature on the vaccine showed superior immunogenicity in mice where the Ad26 vector encoding for the membrane-bound stabilized S protein with a wild-type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-g.

Status: First participants were dosed in Phase 3 trial (ENSEMBLE) evaluating safety and efficacy of Janssen’s COVID-19 vaccine candidate, JNJ-78436735, also known as Ad26.COV2.S. The initiation of the ENSEMBLE trial follows positive interim results from the Company’s Phase 1/2a clinical study, which demonstrated that the safety profile and immunogenicity after a single vaccination were supportive of further development. These results have been submitted to medRxiv and are due to be published online imminently. Based on these results and following discussions with the U.S. FDA, ENSEMBLE will enroll up to 60,000 volunteers across three continents and will study the safety and efficacy of a single vaccine dose versus placebo in preventing COVID-19.

References:

  • Press release: Johnson & Johnson Announces Acceleration of its COVID-19 Vaccine Candidate; Phase 1/2a Clinical Trial to Begin in Second Half of July. Johnson & Johnson (06/10/20).
  • Preprint: Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. bioRxiv (07/30/20).
  • News: Johnson & Johnson starts human safety trial for its COVID-19 vaccine candidate. Reuters (07/30/20).
  • News: Brazil greenlights human trials for J&J’s potential COVID-19 vaccine. Reuters (08/20/20).
  • Publication: Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nature (09/03/20).
  • Press Release: Johnson & Johnson Initiates Pivotal Global Phase 3 Clinical Trial of Janssen’s COVID-19 Vaccine Candidate. JnJ (09/23/20).
  • Publication: Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. Nature (09/28/20).

Candidate: Inactivated virus (CoronaVac)

Sponsors/Developers: Sinovac Biotech Ltd.; Funding by Advantech Capital and Vivo Capital

Location: Brazil, China, Indonesia

Trial identifier: NCT04456595 (Phase III), NCT04352608 (Phase II), NCT04508075 (Phase III), NCT04551547 (Phase I/II)

Description: To develop preclinical in vitro neutralization and challenge models for a candidate SARS-CoV-2 vaccine, SARS-CoV-2 strains were isolated from BALF samples of 11 hospitalized patients. The 11 samples contained SARS-CoV-2 strains that are widely scattered on the phylogenic tree constructed from all available sequences, representing, to some extent, circulating SARS-CoV-2 populations. Strain CN2 was chosen for purified inactivated SARS-CoV-2 virus vaccine development (PiCoVacc) and another 10 strains (termed as CN1, CN3-CN5 and OS1-OS6) as preclinical challenge strains. Of note, the CN1 and OS1 strains are closely related to 2019-nCoV-BetaCoV /Wuhan/WIV04/2019 and EPI_ISL_412973, respectively, which have been reported to cause severe clinical symptoms, including respiratory failure, requiring mechanical ventilation.

Sinovac (Beijing, China), in collaboration with Butantan (Sao Paulo, Brazile), receives approval from the Brazilian National Regulatory Agency, Anvisa, for a Phase III trial of its COVID-19 vaccine candidate, as on July 6, 2020.

Phase II data was published as a preprint on August 10, 2020 – Results from a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the inactivated vaccine (CoronaVac). A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 ug/0.5 mL or 6 ug /0.5mL, or placebo. CoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. CoronaVac showed good immunogenicity with the lower dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules (No T cell data).

Bangladesh has approved a late-stage trial of a potential COVID-19 vaccine developed by China’s Sinovac Biotech Ltd in the hope of being a priority recipient for the jab, the health minister said on Thursday. The trial will involve 4,200 volunteers and half of them will be vaccinated. Indonesia and Brazil are also helping with the Phase III trial as Sinovac has been looking for volunteers outside China where the number of coronavirus cases has dwindled. This pushes the total in phase 3 for this inactivated vaccine to 14,690, as on August 27, 2020.

Brazilian investigators on 31 August 2020 reported it’s been used by 24,000 people in China (with 5% adverse effects, very low fever). The most frequent effect was pain at the injection site and the feverish manifestations did not reach 0.18%. Governor Joao Doria in Brazil added on September 10, 2020, that Phase 2 trials of the potential vaccine had shown an immune response of 98 percent in the elderly. Some 9,000 Brazilian volunteers are participating in the Sinovac vaccine trials, which are being conducted by the Butantan Institute in Sao Paulo city and 11 other locations.

Status: Sinovac announced on 23 September that CoronaVac was approved by the National Medical Products Administration (NMPA) for clinical trial in adolescents and children. This randomized, double-blinded, and placebo-controlled phase I/II clinical trial among adolescents and children between the ages of 3-17 years old was approved by the Ethics Committee of the Hebei Provincial CDC on September 11, 2020, with the trial expected to commence soon. In this clinical trial, low dosage (300SU/dose) and medium dosage (600SU/dose) with two-dose immunization scheduled at 28-day intervals will be adapted.

As per news reports, research with 50,027 volunteers in China showed that the Coronavac vaccine did not show significant adverse reactions. Among people over 60 (422 volunteers), the results showed 97% effectiveness. Instituto Butantan is conducting clinical trials of the vaccine in phase 3 in Brazil on almost 6,000 volunteers. In Brazil, the vaccine was applied to almost 5,600 volunteers with no record of serious adverse reaction. The vaccine developed by Sinovac Life Science is one of the most promising in the world because it uses technology already known and widely applied in other vaccines by the Butantan Institute.

References:

  • Press Release: Sinovac COVID-19 Vaccine Collaboration with Butantan Receives Approval from Brazilian Regulator for Phase III Trial. Businesswire (06 July 2020).
  • Press Release: Sinovac Announces Positive Preliminary Results of Phase I/II Clinical Trials for Inactivated Vaccine Candidate Against COVID-19. Sinovac (06/13/20).
  • Press Release:  Sinovac and Butantan Join Efforts to Advance the Clinical Development of An Inactivated Vaccine for COVID-19 to Phase III (06/11/20).
  • Publication: Development of an inactivated vaccine candidate for SARS-CoV-2. Science (07/03/20).
  • Preprint: Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial. medRxiv (08/11/20).
  • News: Bangladesh approves late-stage trial of China’s Sinovac COVID-19 vaccine candidate. Reuters (08/27/20).
  • News: Sinovac’s vaccine reportedly shows low adverse events following emergency use authorization. News (08/31/20).
  • News: Brazil trials of Sinovac COVID-19 vaccine show promising results: Governor. CNBC (09/10/20).
  • Press Release: Sinovac’s Coronavac, SARS-CoV-2 Vaccine (Vero Cell), Inactivated, Announces Approval for Phase I/II Clinical Trial in Adolescents and Children. Businesswire (09/23/20).
  • News: Study of more than 50,000 volunteers in China shows Coronavac safety. Sao Paulo’s State Government (09/23/20).
  • Press Release: Sinovac’s Coronavac, SARS-CoV-2 Vaccine (Vero Cell), Inactivated, Announces Approval for Phase I/II Clinical Trial in Adolescents and Children. Businesswire (09/23/20).

Candidate: Non-Replicating Viral Vector AZD1222 (ChAdOx1)

Sponsors/Developers: The University of Oxford, The Jenner Institute | AstraZeneca; BARDA; UK Ministry of Health

Location: UK, Brazil, India.

Trial Identifier: NCT04400838 (COV002);Phase 1/2: NCT04400838; ISRCTN: 15281137; NCT04516746 (Phase 2/3); NCT04536051 (Phase 3, COV003).

Description: Developed at the University of Oxford’s Jenner Institute, and working with the Oxford Vaccine Group, ChAdOx1 nCoV-19 uses a viral vector based on a weakened version of the common cold (adenovirus) containing the genetic material of SARS-CoV-2 spike protein. After vaccination, the surface spike protein is produced, which primes the immune system to attack COVID-19 if it later infects the body. The recombinant adenovirus vector (ChAdOx1) was chosen to generate a strong immune response from a single dose and it is not replicating, so cannot cause an ongoing infection in the vaccinated individual. Vaccines made from the ChAdOx1 virus have been given to more than 320 people to date and have been shown to be safe and well tolerated, although they can cause temporary side effects such as a temperature, flu-like symptoms, headache or sore arm.

On July 02, 2020, Sarah Gilbert, professor of vaccinology at the university, said 8,000 volunteers had been enrolled for the Phase III of its trial into the vaccine, AZD1222, which was licensed to AstraZeneca. Gilbert said she hoped that her Oxford vaccine would make progress earlier, but was not more specific as she said the timeline for when the vaccine might be ready depends on the results of the trial.

Recently published trial results show very encouraging safety data, neutralizing antibody and spike protein specific T cell response. The phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein was compared with a meningococcal conjugate vaccine (MenACWY) as control. 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose and after a booster dose, all participants had neutralising activity. These results, together with the induction of both humoral and cellular immune responses, support large scale evaluation of this candidate vaccine in an ongoing phase 3 programme.

Status: On September 09, 2020, AstraZeneca put the vaccine trial on hold over safety concern after an unexplained illness in a study participant. “Our standard review process was triggered and we voluntarily paused vaccination to allow review of safety data by an independent committee,” company spokeswoman Michele Meixell said in an emailed statement. The volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. On 12 September, 2020, Astrazeneca informed that the clinical trials will resume across all UK clinical trial sites. The independent review process had concluded and following the recommendations of both the independent safety review committee and the UK regulator, the MHRA, the trials will recommence in the UK. The statement said “Globally some 18,000 individuals have received study vaccines as part of the trial. In large trials such as this, it is expected that some participants will become unwell and every case must be carefully evaluated to ensure careful assessment of safety. “.

Symptoms that prompted the pause trials probably weren’t related to the shot itself, according to documents sent to participants, news reports suggest. Safety reviews were carried out when participants in the Oxford study developed unexplained neurological symptoms including limb weakness or “changed sensation,” a participant information sheet posted online by Oxford shows.

The vaccine platform will also be tested in inhaled form alongside the candidate from Imperial College London.

References:

  • Preprint: A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains. bioRxiv (04/13/20).
  • Preprint: ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRxiv (05/13/20).
  • Publication: Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet (07/20/20).
  • Publication: ChAdOx1 nCoV-19 vaccine induced antigen-specific antibody and T cells responses after a single dose and enhanced responses after a booster immunization in mice and pigs. Nature (07/27/20).
  • Publication: ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature (07/30/20).
  • Publication: A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell (08/19/20).
  • STAT News: Covid-19 vaccine trial participant had serious neurological symptoms, but could be discharged today, AstraZeneca CEO says. STAT (09/09/20).
  • Reuters, NYT: AstraZeneca puts leading COVID-19 vaccine trial on hold over safety concern (09/09/20).
  • Oxford Univ: University of Oxford resumes vaccine trial (09/09/20).
  • News: Vaccine Trial Illness Unlikely to Be Linked to Shot, Oxford Says. (09/16/20).
  • Imperial College: Landmark coronavirus study to trial inhaled Imperial and Oxford vaccines. (09/14/20).

Candidate: Recombinant Protein Vaccine formulation 1 or 2 with adjuvant 1 or 2, or without adjuvant.

Sponsors/Developers: Sanofi Pasteur, GlaxoSmithKline.

Location: United States.

Trial Identifier: NCT04537208 (Phase 1/2)

Description: Pre-clinical studies showed promising safety and immunogenicity. The Phase 1/2 clinical trial is a randomised, double blind and placebo-controlled trial designed to evaluate the safety, reactogenicity (tolerability) and immunogenicity (immune response) of the COVID-19 vaccine candidate. A total of 440 healthy adults are being enrolled in the trial across 11 investigational sites in the United States. Pending positive Phase 1/2 data, companies aim to move into Phase 3 by end of 2020. The Companies anticipate first results in early December 2020, to support the initiation of a Phase 3 trial in December 2020.  If these data are sufficient for licensure application, it is planned to request regulatory approval in the first half of 2021. Sanofi and GSK are scaling up manufacturing of the antigen and adjuvant with the target of producing up to one billion doses in 2021.

Status: The partners plan to supply a significant portion of total worldwide available supply in 2021/2022 to COVAX, the vaccines pillar of the ACT-Accelerator (Access to COVID‐19 Tools), a global collaboration of leaders of governments, global health organisations, businesses and philanthropies to accelerate development, production, and equitable access to COVID-19 tests, treatments, and vaccines.

References:

  • Press Relase: Sanofi and GSK initiate Phase 1/2 clinical trial of COVID-19 adjuvanted recombinant protein-based vaccine candidate (09/03/20).
  • Press Release: Sanofi and GSK to join forces in unprecedented vaccine collaboration to fight COVID-19 (04/14/20).

Candidate: Sputnik V (Gam-COVID-Vac)

Sponsors/Developers: Gamaleya National Research Institute of Epidemiology and Microbiology

Location: Russia, a number of Middle Eastern (UAE and Saudi Arabia), and Latin American countries (Brazil and Mexico).

Trial identifier: NCT04437875 (Phase 1/2), NCT04436471 (Phase 1/2), NCT04530396 (Phase 3)

Description: Russian adenovirus vector-based vaccine was registered by the Russian Ministry of Health on August 11 and became the first registered COVID-19 vaccine on the market. The Gamaleya Center successfully developed and registered an adenoviral vector-based vaccine against Ebola. Another adenoviral vector-based vaccine against Middle East Respiratory Syndrome (MERS) is in advanced stages of clinical trials.

As per the developers, Phase 1 and 2 clinical trials of the vaccine have been completed on August 1, 2020. All the volunteers are feeling well, no unforeseen or unwanted side effects were observed. The vaccine induced strong antibody and cellular immune response. Not a single participant of the current clinical trials got infected with COVID-19 after being administered with the vaccine. The high efficacy of the vaccine was confirmed by high precision tests for antibodies in the blood serum of volunteers (including an analysis for antibodies that neutralize the coronavirus), as well as the ability of the immune cells of the volunteers to activate in response to the spike S protein of the coronavirus, which indicates the formation of both antibody and cellular immune vaccine response.

Phase 3 clinical trial involving more than 2,000 people in Russia, a number of Middle Eastern (UAE and Saudi Arabia), and Latin American countries (Brazil and Mexico) will start on August 12.

Russia has released no scientific data on its testing and experts are unable to verify the vaccine’s claimed safety or effectiveness.

Status: On August 28, 2020, the trial was registered for Phase 3 – 40,000 participants, limited outcome measures, including adults with no upper age restriction, to be conducted in Russia.

NCT04436471 and NCT04437875: Two open, non-randomised phase 1/2 studies at two hospitals in Russia (76 participants to the two studies) – A heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for SARS-CoV-2 spike glycoprotein (rAd26-S and rAd5-S). The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants.

References:

  • Sputnik Vaccine official website.
  • Publication: Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet (09/04/20).
  • News: The first batch of the Sputnik V coronavirus vaccine released into civil circulation Ministry of Health of the Russian Federation (09/08/20).

Candidate: Inactivated SARS-CoV-2 vaccine BBIBP-CorV

Sponsors/Developers: Sinopharm, Wuhan Institute of Biological Products

Location: UAE, Bahrain, Peru, Morocco, Argentina

Trial identifierChiCTR2000034780 (Phase 3)

Description: Three SARS-CoV-2 strains from the BAL samples or throat swabs of 3 hospitalized patients from the recent COVID-19 outbreak were isolated to develop preclinical in vitro neutralization and challenge models for an inactivated SARS-CoV-2 vaccine candidate (from Vero cells). The 19nCoV-CDC-Tan-HB02 (HB02) strain showed the most optimal replication and generated highest virus yields in Vero cells among three viral strains and was used for the further development of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV). BBIBP-CorV induced high levels of neutralizing antibodies titers in animal models. Two-dose immunization with 2 ug/dose BBIBP-CorV efficiently protects rhesus macaques. It is efficiently produced, genetically stable, and seems to be safe in animals

The first WHO enlisted global clinical Phase III trial of Sinopharm CNBG’s inactivated vaccine to combat COVID-19 has started in July in Abu Dhabi. UAE Health Authorities have issued a permit for up to 15,000 volunteers to participate and G42 Healthcare and SEHA are working towards achieving a minimum of 5,000 participants for the trials.

They launched the Phase 3 trials in the UAE in July, and in Peru and Morocco the following month. Sinopharm’s chairman said in August that the vaccine could potentially be ready for public use by the end of 2020.

As on August 12, 2020, the Phase III trials of the inactivated vaccine in the UAE have reached the target of 15,000 volunteers in less than a month, with individuals from 102 nationalities participating in the program. Sinopharm Group Biological Products, noted, “The speed of these trials to date and the incredible diversity of volunteers who have been vaccinated has fully reinforced our decision that the UAE was a perfect location to test our inactivated vaccine and reach the widest demographic range of volunteers.”.

The report on the preliminary assessment of the safety outcomes 28 days and immunogenicity outcomes 14 days after 3 doses in a phase 1 trial and 2 doses in a phase 2 trial of an inactivated COVID-19 vaccine candidate in healthy adults in China was published on August 13, 2020. Patients had a low rate of adverse reactions (only 15% of people in total; fever = 3%) and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. A phase 3 trial has been initiated (ChiCTR2000034780), which will provide information on immune persistence and efficacy.

Status: The UAE’s phase 3 trial was fully recruited by Aug 30. A whopping 31,000 people have participated altogether since July 16, with 120 nationalities. The UAE has granted an Emergency Use Authorization six weeks after late-stage studies began. The health authorities said the experimental vaccine will be administered to frontline healthcare workers who are dealing with cases of COVID-19 and are at higher risk of exposure.

References:

  • Publication: Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell (08/06/20).
  • News: World’s First Phase III Clinical Trial of COVID-19 Inactivated Vaccine Begins in UAE. Businesswire (07/17/20).
  • News: UAE’s phase III Covid-19 inactivated vaccine trial (Sinopharm) reaches milestone of 15,000 volunteers. Khaleejtimes (08/12/20).
  • Publication: Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA (08/13/20).
  • News: China Sinopharm’s COVID-19 vaccine starts phase-3 clinical trials in Argentina. CGTN (08/22/20).
  • News: Bahrain starts Phase III trial of Sinopharm’s Covid-19 vaccine. Clinicaltrialsarena (08/24/20).
  • News: 31,000 volunteers take part in UAE vaccine trials. The National (08/24/20).
  • News: UAE announces emergency approval for use of COVID-19 vaccine. BioSpace (09/14/20).

Candidate: Non-replicating viral vector (Adenovirus type 5 vector) vaccine

Sponsors/Developers: CanSino Biologics | Beijing Institute of Biotechnology (Beijing); Jiangsu Province CDC, Hubei Provincial CDC, Zhongnan Hospital, Canadian Center for Vaccinology

Location: China, Canada, Pakistan

Trial identifier: LIMITED APPROVAL (Military use only). NCT04313127 (Phase 1), NCT04398147 (Phase 2, Canada), NCT04341389 (Phase 2, China), NCT04526990 (Phase 3, Pakistan)

Description: Recombinant adenovirus type 5 (Ad5) vector expressing the SARS-CoV-2 S protein: The vaccine is a replication defective Ad5 vectored vaccine expressing the spike glycoprotein of SARS-CoV-2. An optimised full-length spike gene based on Wuhan-Hu-1 (GenBank accession number YP_009724390) was cloned with the tissue plasminogen activator signal peptide gene into an E1 and E3 deleted Ad5 vector and constructed the Ad5 vectored COVID-19 vaccine using the Admax system from Microbix Biosystem (Toronto, ON, Canada). The Ad5 vectored COVID-19 vaccine was manufactured as a liquid formulation containing 5×1010 viral particles per 0.5 mL in a vial.

On Monday, June 29, the company developing a vaccine called Ad5-nCoV, CanSino, announced it had been authorized for use in the military by the country’s Central Military Commission. On 20 July 2020, results were published for the randomized, double-blind, placebo-controlled, phase 2 trial of the candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine was done in a single center in Wuhan, China (ClinicalTrials.gov, NCT04341389). 508 participants were randomly assigned to receive the vaccine (1x10E11 viral particles n=253; 5x10E11 viral particles n=129) or placebo (n=126). Both doses of the vaccine induced significant neutralizing antibody responses to live SARS-CoV-2. Specific interferon gamma enzyme-linked immunospot assay responses post vaccination was observed in 227 (90%) and 113 (88%) of viral particles dose groups. Severe adverse reactions were observed in 24 (9%) participants and one (1%) participant respectively.

CanSino’s Phase 3 trial was registered on 26 August 2020, with 40000 target participants, centered out of Pakistan. On August 20, another phase 3 trial was announced by CanSino: 10,000 participants this time. This is in addition to the 5000 in Saudi Arabia, 625 in Russia and unknown number in Mexico: their goal was 40000.

Status: The Phase III trial of the Ad5-nCoV vaccine candidate has been launched in Moscow, following health ministry authorization. CanSino will work with NPO Petrovax Pharm to conduct the trials in Russia. The Russian approval comes after CanSino and the National Research Council (NRC) of Canada terminated their collaboration on the development of the vaccine. CanSino plans to test its vaccine candidate in multiple countries globally.

References:

  • Publication: Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial The Lancet (06/13/20).
  • Preprint: A single dose of an adenovirus-vectored vaccine provides complete protection of the upper and lower respiratory tracts against SARS-CoV-2 challenge (06/18/20).
  • Publication: Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. (07/20/20).
  • News: CanSino has its 1st phase 3 trial Covid-19 vaccine partner (Saudi Arabia & 5,000 people) (08/10/20).
  • Publication: A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge. Nature (08/14/20).
  • News: Pakistan gives go-ahead to Phase 3 COVID-19 vaccine trial (08/20/20).
  • News: Russia approves Phase III trial of CanSino’s Covid-19 vaccine (09/02/20).

Candidate: Four BNT162 Vaccines – BNT162 a1, b1, b2, and c2

Sponsors/Developers: BioNTech RNA Pharmaceuticals GmbH | Fosun Pharma | Pfizer

Location: Germany, U. S.

Trial identifier: NCT04368728 (Phase1/2/3); NCT04380701 (Phase 1/2)

Description: BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.

Pfizer’s press release on July 01, 2020 stated they will pick a lead candidate from the 4 to go into a phase 2b/3 global trial with 30,000 people, possibly starting by the end of July if they get the green light from regulatory agencies.

Preprint published on July 20, 2020 presents antibody and T cell responses after BNT162b1 vaccination from a second, non-randomized open-label phase 1/2 trial in healthy adults, 18-55 years of age (NCT04380701). Two doses of 1 to 50 ug of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Neutralization assays conducted with 17 different RBD variants including the dominant spike variant D614G – all 17 variants efficiently neutralized by BNT162b1 immune sera. 34/36 (94.4%) had RBD-specific CD4+ T cell responses and 29/36 (80.6%) had RBD-specific CD8+ T cell responses. Mean fraction of RBD-specific T cells within total circulating T cells by BNT162b1 was substantially higher than that observed in 6 convalescent COVID-19 patients.

As on July 27, 2020, Pfizer and BioNTech announced their lead mRNA vaccine candidate to commence pivotal Phase 2/3 global study [BNT162b2 (full spike protein) instead of BNT162b1 (trimerized RBD)] – The companies decided to advance nucleoside-modified messenger RNA (modRNA) candidate BNT162b2, which encodes an optimized SARS-CoV-2 full-length spike glycoprotein, at a 30 µg dose level in a 2 dose regimen into Phase 2/3 Study. Phase 2/3 study of up to 30,000 participants aged 18 – 85 years started in U.S. and expected to include approximately 120 sites globally. During preclinical and clinical studies of four BNT162 RNA vaccine candidates, BNT162b1 and BNT162b2 emerged as strong candidates based on assessments of safety and immune response. Pfizer and BioNTech selected BNT162b2 as the candidate to progress to a Phase 2/3 study based on the totality of available data from preclinical and clinical studies, including select immune response and tolerability parameters.

Results for another candidate, BNT162b1, were published on 12 August 2020 (NCT04368728). Data report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among 45 healthy adults, 18 to 55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 ug, 30 ug, or 100 ug of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes trimerized SARS-CoV-2 Spike RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 ug was not administered due to increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared to the 30 ug dose. Geometric mean neutralizing titers reached 1.9- to 4.6-fold that of a panel of COVID-19 convalescent human sera at least 14 days after a positive SARS-CoV-2 PCR. There was no data on T-cells.

BNT162b2, which encodes a prefusion stabilized membrane-anchored SARS-CoV-2 full-length spike was selected over BNT162b1, which encodes a secreted trimerized RBD for Phase 2/3. Additional safety and immunogenicity data is presented from the US Phase 1 trial that supported selection of the vaccine candidate advanced to a pivotal Phase 2/3 safety and efficacy evaluation. BNT162b2 was associated with less systemic reactogenicity, particularly in older adults. In both younger and older adults, the 2 vaccine candidates elicited similar dose-dependent neutralizing titers , higher than convalescent sera.

Immunization of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralization titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralizing geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNg+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunized rhesus macaques from infectious SARS-CoV-2 challenge.

Status: Pfizer and BioNTech Propose to expand the enrollment of their Phase 3 pivotal COVID19 vaccine trial to up to approximately 44,000 participants which also allows for the enrollment of new populations.

Pfizer has said that Phase III clinical trial participants were experiencing mild-to-moderate side effects with its investigational Covid-19 vaccine candidate. On an investor conference call, the company executives noted that more than 12,000 study participants had received a second dose of the vaccine candidate, according to Reuters. The company has recruited more than 29,000 volunteers so far. An independent data monitoring committee could recommend pausing the study at any time, but has not done so till date, the company said.

References:

  • Preprint: Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. medRxiv (07/01/20).
  • Press Release: Pfizer and BioNTech Granted FDA Fast Track Designation for Two Investigational mRNA-based Vaccine Candidates Against SARS-CoV-2. Businesswire (07/13/20).
  • Preprint: Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine. medRxiv (07/20/20).
  • Press Release: PFIZER and BIONTECH announce agreement with the United Kingdom for 30 million doses of mRNA-based vaccine candidate against SARS-COV-2. Pfizer (07/20/20).
  • Press Release: Pfizer and BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 and Commence Pivotal Phase 2/3 Global Study. BioNTech (07/27/20).
  • Publication: Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature (08/12/20).
  • Publication: RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study. medRxiv (08/21/20).
  • Preprint: A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates. bioRxiv (09/19/20).
  • Press Release: PFIZER AND BIONTECH PROPOSE EXPANSION OF PIVOTAL COVID-19 VACCINE TRIAL. Pfizer (09/12/20).
  • Reuters: Pfizer says Covid-19 vaccine showed moderate side effects. Reuters (09/16/20).

Candidate: Lipid nanoparticle (LNP) encapsulated mRNA (mRNA-1273)

Sponsors/Developers: Moderna, Inc. | National Institute of Allergy and Infectious Diseases (NIAID); Funding from the Biomedical Advanced Research and Development Authority (BARDA); Kaiser Permanente Washington Health Research Institute

Location: U.S.

Trial identifier: NCT04283461 (Phase 1) NCT04405076 (Phase 2), NCT04470427 (Phase 3)

Description: mRNA-1273 is an mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein, which was selected by Moderna in collaboration with investigators from Vaccine Research Center (VRC) at the NIAID. The first clinical batch, which was funded by the Coalition for Epidemic Preparedness Innovations, was completed on February 7, 2020 and underwent analytical testing; it was shipped to NIH on February 24, 42 days from sequence selection. The first participant in the NIAID-led Phase 1 study of mRNA-1273 was dosed on March 16, 63 days from sequence selection to Phase 1 study dosing.

Results for the first 45 people in the Moderna/NIH Covid-19 vaccine phase 1 trial (NCT04283461) published. The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. The Phase 3 trial for the Moderna/NIH Covid-19 vaccine is registered: NCT04470427, to start July 27, 30,000 individuals, 87 locations in the US. Scientists have noted the absence of data for the most vulnerable older (>55) population; Second dose being necessary; Safety profile being less than desirable; Durability of neutralizing Ab not being encouraging (decline from day 43~57); and very low CD8 T-cell responses as critical observations.

On July 28, 2020, Moderna published results from animal studies – Nonhuman primates received 10 or 100 ug of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.

On August 26, 2020, Moderna said its coronavirus vaccine showed promising results in small trial of elderly patients. The latest results are from an analysis of 20 additional older volunteers who were given a 100ug dose. According to the company, the immune response was similar across age groups of 56 to 70, above 70 and 18 to 55 years. Data showed that the older adults’ antibody levels were two to three times higher than those found in patients who had recovered from Covid-19.

Status: The Phase 3 COVE study of 30,000 volunteers in the U.S. being conducted with NIH and BARDA has enrolled 25,296 participants as of September 16, 2020; 10,025 participants have received their second vaccination to date. To provide additional transparency in context of pandemic, Phase 3 protocol now available online.

References:

  • Publication: An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. NEJM (07/14/20).
  • Preprint: mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. bioRxiv (06/11/20).
  • Press Release: Moderna Announces Expansion of BARDA Agreement to Support Larger Phase 3 Program for Vaccine (mRNA-1273) Against COVID-19. Moderna (07/26/20).
  • Publication: Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. NEJM (07/28/20).
  • Press Release: Moderna says its coronavirus vaccine shows promising results in small trial of elderly patients. Moderna (08/27/20).
  • Website: Additional COVE Study Information. Moderna (Accessed 09/25/20).

Candidate: Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152, Covaxin)

Sponsors/Developers: Bharat Biotech International Limited, ICMR (Indian Council of Medical Research).

Location: India.

Trial identifier: NCT04471519 (Phase1/2), CTRI/2020/07/026300 (Phase 1/2).

Description: COVAXIN, Indias COVID-19 vaccine by Bharat Biotech is developed in collaboration with the ICMR – National Institute of Virology (NIV). The indigenous, inactivated vaccine is developed and manufactured in Bharat Biotechs BSL-3 (Bio-Safety Level 3) high containment facility. The vaccine received DCGI approval for Phase I and II Human Clinical Trials and the trials will commence across India from July 2020.

As on August 17, Covaxin has demonstrated an encouraging safety profile in a Phase I clinical trial conducted in the country. Preliminary Phase I trial results showed that the vaccine is safe. Trial investigators are said to be collecting blood samples to analysze the vaccine’s immunogenicity. The Phase I study involves 375 volunteers at 12 sites across the country.

A recently published preprint on the development and evaluation of safety and immunogenicity of this whole virion inactivated SARS-CoV-2 vaccine, adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations (3 ug and 6 ug), in all three species (mice, rats, and rabbits) with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-g+ CD4 T lymphocyte response.

Status: Bharat Biotech has obtained regulatory approval to advance its candidate into Phase II clinical trials. The Phase II trials will enroll 380 participants.

References:

  • Preprint: Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion Inactivated SARS-CoV-2 Vaccine – BBV152. bioRxiv (09/09/20).
  • News: Bharat Biotech’s Covaxin vaccine yields positive Phase I data. ClinicalTrialsArena (08/17/20).
  • News: Bharat Biotech gets approval to progress Covaxin to Phase II trials. ClinicalTrialsArena (09/07/20).
  • Press release: Bharat Biotech, Thomas Jefferson University pursue a promising vaccine candidate against COVID-19. Bharat Biotech (05/20/20).

Table: All 34 vaccine candidates in clinical evaluation (as of September 08, 2020).

Updated: 28 September, 2020.

  • Anti-CD73 molecule CPI-006 activates B cell responses to SARS-CoV-2 and may enhance and prolong antibody responses [Link] (09/28/20)
  • Mix of ultrapotent antibodies isolated from recovered COVID-19 patients protects against SARS-CoV-2 challenge in hamsters via multiple mechanisms [Link] (09/28/20)
  • Hamsters treated with human monoclonal antibody CV07-209 either before (prophylactic) or after infection (therapeutic) shows potent effects [Link] (09/28/20)
  • New in vitro selection method isolates antibody-like proteins, monobodies, that can capture and neutralize SARS-CoV-2 [Link] (09/21/20)
  • Roche’s Actemra meets primary endpoint in phase 3 EMPACTA trial with 44% patients less likely to progress to mechanical ventilation or death [Link] (09/21/20)
  • Lilly’s neutralizing antibody LY-CoV555 increases viral clearance and leads to reduced rate of hospitalization in a phase 2 trail [Link] (09/21/20)
  • Roche’s tocilizumab trial COVACTA reports no improvement in clinical status or mortality in hospitalized COVID-19 pneumonia patients [Link] (09/21/20)
  • University of Pittsburgh School of Medicine report on an antibody component as the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 [Link] (09/15/20)
  • BD-368-2, a SARS-CoV-2 neutralizing antibody with high potency, is highly effective at low dosages in hamsters with severe disease [Link] (09/15/20)
  • REGN-COV2 antibody cocktail to be evaluated in a phase 3 trial by RECOVERY group [Link] (09/14/20)
  • Humanized single domain antibodies can block association between SARS-CoV-2 Spike receptor-binding domain and viral entry receptor ACE2 [Link] (09/11/20)
  • Alpaca-derived, single domain antibody fragment (nanobody) targeting Spike RBD neutralizes SARS-CoV-2 by blocking ACE2 interaction [Link] (09/04/20)
  • Kevzara (sarilumab) phase 3 trial fails to meet endpoints in severely or critically ill patients [Link] (09/02/20)
  • First case-control results for humaneered anti-GM-CSF monoclonal antibody Lenzilumab shows 80% reduction in risk of ventilation or death [Link] (09/01/20)

Monoclonal antibodies provide an alternative avenue for the prevention of COVID-19, as the vaccine development process can take at least 12-18 months. Neutralizing mAbs to SARS-CoV-2 have the potential for both therapeutic and prophylactic applications and can help to guide vaccine design and development. Numerous research groups have isolated mAbs (most often from the B cells of patients who have recently recovered from SARS-CoV-2, and in some cases from individuals who were infected with SARS-CoV in 2003). It is also possible to generate effective mAbs by immunization of humanized mice. Modern methods allow the rapid identification of pathogen-specific B cells and recovery of immunoglobulin heavy chain and light chain genes that can be expressed to produce mAbs, usually in the form of IgG. The main target of SARS-CoV-2 neutralizing mAbs is the surface spike glycoprotein that mediates viral entry into host cells. Essentially all mAbs of interest target this protein. Viral infection is mediated by the interaction between the viral spike and the angiotensin-converting enzyme 2 (ACE 2) receptor found on numerous cell types, but neutralizing mAbs block this event. Immune system of nearly everyone who recovers from COVID-19 produces antibodies against SARS-CoV-2, the novel coronavirus that causes this easily transmitted respiratory disease. mAbs are currently used to treat a variety of conditions, including asthma, cancer, Crohn’s disease, and rheumatoid arthritis. One advantage of this class of therapeutics is that the timelines for their development, testing, and approval are typically shorter than those for drugs made of chemical compounds, called small molecules. Because of these and other factors, many experts think antibody-based therapies may offer one of the best near-term options for developing safe, effective treatments for COVID-19 [1].


Select strategies are detailed in the section below:

Candidate: Tocilizumab (Actemra/RoActemra)

Developers: Roche, Genentech

Locations: USA, Canada, Denmark, France, Germany, Italy, Netherlands, Spain, UK.

Clinical Trial IDs: COVACTA/NCT04320615 (phase III), REMDACTA/NCT04409262 (phase III), EMPACTA/NCT04372186 (phase III)

Description: Actemra/RoActemra was the first approved anti-IL-6 receptor biologic available in both intravenous and subcutaneous formulations for the treatment of adult patients with moderate-to-severe active rheumatoid arthritis. On 19 March, Roche announced the initiation of COVACTA- a clinical trial to evaluate the safety and efficacy of intravenous Actemra/RoActemra (tocilizumab) plus SoC in hospitalised adult patients with severe COVID-19 pneumonia compared to placebo plus SoC. COVACTA is a double-blind, placebo-controlled phase III study in approximately 450 adult patients hospitalised with severe COVID-19 pneumonia. REMDACTA is a two-armed global phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of Actemra/RoActemra plus remdesivir, versus placebo plus remdesivir in hospitalised patients with severe COVID-19 pneumonia receiving Soc.

Genentech’s EMPACTA will evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia. EMPACTA is the first global Phase III trial with a focus on enrolling largely underserved and minority patients.

On July 29, 2020, Roche announced that the trial did not meet its primary endpoint of improved clinical status in patients with COVID-19 associated pneumonia, or the key secondary endpoint of reduced patient mortality. The study was the first global, randomised, double-blind, placebo-controlled phase III trial investigating in this setting. Roche remains committed to continuing the clinical trial program to further explore Actemra/RoActemra in other treatment settings, including in combination with an antiviral.

Status: In a preprint published September 12, 2020, authors reported that the COVACTA trial (NCT04320615) in hospitalized COVID-19 pneumonia patients (Overall 452 – 94 tocilizumab-treated and 144 placebo-treated), tocilizumab did not improve clinical status or mortality. Potential benefits in time to hospital discharge and duration of ICU stay are being investigated in ongoing clinical trials.

On September 17, 2020, EMPACTA became the first global Phase III trial to show efficacy with Actemra in COVID-19 associated pneumonia. There was no statistical difference in mortality between patients who received Actemra or placebo. The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the Actemra/RoActemra arm versus 19.3% in the placebo arm. The EMPACTA study did not identify any new safety signals for Actemra/RoActemra. Approximately 85% of the 389 patients were from minority racial and ethnic groups.

References:

  • Publication: Subcutaneous tocilizumab treatment in patients with severe COVID-19–related cytokine release syndrome: An observational cohort study. The Lancet (07/01/20).
  • Press Release: Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia. Roche (07/29/20).
  • Preprint: Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia. medRxiv (9/12/20).
  • Press Release: Genentech’s Phase III EMPACTA Study Showed Actemra Reduced the Likelihood of Needing Mechanical Ventilation in Hospitalized Patients With COVID-19 Associated Pneumonia. Genentech (9/17/20).

Candidate: VIR-7831 and VIR-7832

Developers: Vir Biotechnology, GlaxoSmithKline

Locations: United States

Clinical Trial IDs: NCT04545060 (Phase 2/3)

Description: VIR-7831 is a monoclonal antibody that has demonstrated the ability to neutralize SARS-CoV-2 live virus in vitro. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (also known as SARS), indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop. VIR-7831 has been engineered to enhance bioavailability and have an extended half-life.

VIR-7832 is a monoclonal antibody that has demonstrated the ability to neutralize SARS-CoV-2 live virus in vitro. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (also known as SARS), indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop. VIR-7832 has been engineered to enhance bioavailability, have an extended half-life and to potentially function as a T cell vaccine

Status: On August 31, 2020, Vir Biotechnology and GSK announced start of Phase 2/3 study of the antibody treatment. The first patient was dosed last week in a Phase 2/3 study with VIR-7831 (also known as GSK4182136), a fully human anti-SARS-CoV-2 monoclonal antibody, for the early treatment of COVID-19 in patients who are at high risk of hospitalization. The aim of the COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) study, which will enroll approximately 1,300 patients worldwide who have early symptomatic infection, is to assess whether VIR-7831, as a single-dose monoclonal antibody, can prevent hospitalization due to COVID-19. Initial results may be available before the end of this year.

References:

  • Website: Vir Bio’s antibody pipeline (accessed 09/21/20).
  • Press release: GSK and Vir Biotechnology enter collaboration to find coronavirus solutions (04/06/21).
  • Press Release: Vir Biotechnology and GSK Start Phase 2/3 Study of COVID-19 Antibody Treatment. Vir Biotechnology (09/14/20).

Candidate: Lenzilumab

Developers: Humanigen

Locations: United States

Clinical Trial IDs: NCT04351152 (Phase 3)

Description: Lenzilumab is a first-in-class Humaneered recombinant mAB targeting human GM-CSF, with potential immunomodulatory activity, high binding affinity in the picomolar range, 94% homology to human germline, and has low immunogenicity. Following intravenous administration, lenzilumab binds to and neutralizes GM-CSF, preventing GM-CSF binding to its receptor, thereby preventing GM-CSF-mediated signaling to myeloid progenitor cells. Lenzilumab has been studied across 4 completed clinical trials in healthy volunteers, and persons with asthma, rheumatoid arthritis, and chronic myelomonocytic leukemia.  A total of 113 individuals received lenzilumab in these trials; lenzilumab was very well tolerated with a low frequency and severity of adverse events.  

Lenzilumab has been shown to have a protective effect against cytokine release syndrome associated with CAR-T therapy. It’s believed that Lenzilumab can aid cytokine-mediated immunopathology of lung injury and ARDS.

Early results from the first 12 patients who received lenzilumab at Mayo Clinic locations showed 11 of 12 patients (92%) had clinical improvement, with a median discharge time of 5 days. Oxygenation was also improved in patients taking lenzilumab.

Humanigen now expects to complete enrolment of the 300 subjects this month with topline results due in the fourth quarter. Statements regarding the potential that lenzilumab will receive an Emergency Use Authorization in 2020 and commence commercialization, and regarding the potential additional manufacturing capacity afforded by the collaboration beginning in 2021.

Status: On September 1, 2020, Lenzilumab is being evaluated in an ongoing Phase III trial and was selected by the NIH for its COVID-19 Big Effect Trial. 80% reduction in relative risk of invasive mechanical ventilation and/or death in patients treated with lenzilumab compared to the control group. Median time to resolution of acute respiratory distress syndrome (ARDS) reduced to one day for patients treated with lenzilumab versus eight days in control group. Lenzilumab patients discharged from the hospital in less than half the time compared with control group. The study involved a total of 39 patients, including 12 treated with lenzilumab, and 27 contemporaneous matched control patients who received standard of care treatment.

References:

  • Preprint: First Clinical Use of Lenzilumab to Neutralize GM-CSF in Patients with Severe COVID-19 Pneumonia. medRxiv (14/06/20).
  • Press release Humanigen Expands Phase III Study of Lenzilumab in COVID-19 to Brazil (10/08/2020).
  • Press release: Humanigen Reports Additional Analysis of Lenzilumab in Severe and Critical COVID-19 Patients Humanigen (16/06/2020).
  • Press release: Lenzilumab COVID-19 Case-Control Study Published in Mayo Clinic Journal. Humanigen (01/09/2020).
  • Press release: Humanigen says review of lenzilumab Phase 3 study of COVID-19 by data safety monitoring board gets green light to continue. Humanigen (14/09/20).
  • Press release: Humanigen and Lonza Announce Collaboration to Expand Manufacturing of Humanigen’s COVID-19 Therapeutic Candidate Lenzilumab. Humanigen (15/09/20).

Candidate: COV2-2196 and COV2-2130, AZD7442 (AZD8895 + AZD1061)

Developers: Astrazeneca, Vanderbilt University Medical Center, Parexel

Locations: United Kingdom

Clinical Trial IDs: NCT04507256 (Phase 1)

Description: AZD7442 is a combination of two mAbs derived from convalescent patients with SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the mAbs were optimized by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extended mAbs should afford at least six months of protection from COVID-19. The mAbs were shown preclinically to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease. The two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner.

Status: On August 25, AstraZeneca began Phase 1 trial for mAbs combination. The trial will evaluate the safety, tolerability and pharmacokinetics of AZD7442. The trial will include up to 48 healthy participants in the UK aged 18 to 55 years and is funded by the Defense Advanced Research Projects Agency (DARPA), part of the US Department of Defense, and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.

References:

  • Press Release: Vanderbilt, AstraZeneca collaborate on new COVID-19 antibody research. Astrazeneca (06/09/20).
  • Publication: Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature (07/15/20).
  • Press Release: Phase I clinical trial initiated for monoclonal antibody combination for the prevention and treatment of COVID-19. Astrazeneca (08/25/20).

Candidate: REGN10933 and REGN10987

Developers: Regeneron Pharmaceuticals

Locations: United States

Clinical Trial IDs: NCT04425629 (Phase 1), NCT04426695 (Phase 1), NCT04519437 (Phase 1)

Description: REGN-COV2 comprises two mABs (REGN10933 and REGN10987) and was designed specifically by Regeneron scientists to block infectivity of SARS-CoV-2, the virus that causes COVID-19. Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s proprietary VelocImmunemice, which have been genetically-modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19. They selected the two most potent, non-competing and virus-neutralizing antibodies to create REGN-COV2 and have scaled up this dual-antibody cocktail for clinical use with the company’s in-house VelociMaband manufacturing capabilities. REGN-COV2’s two antibodies bind non-competitively to the critical receptor binding domain of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population.

Regeneron announced the initiation of  Phase 3 trial will evaluate REGN-COV2’s ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient (such as the patient’s housemate), and is being run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). REGN-COV2 has also moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail’s ability to treat hospitalized and non-hospitalized (or “ambulatory”) patients with COVID-19. This clinical progress follows a positive review from the Independent Data Monitoring Committee of REGN-COV2 Phase 1 safety results in an initial cohort of 30 hospitalized and non-hospitalized patients with COVID-19. The Phase 3 prevention trial is being conducted at approximately 100 sites and is expected to enroll 2,000 patients in the U.S.; the trial will assess SARS-CoV-2 infection status. The two Phase 2/3 treatment trials in hospitalized (estimated enrollment =1,850) and non-hospitalized (estimated enrollment =1,050) patients are planned to be conducted at approximately 150 sites in the U.S., Brazil, Mexico and Chile, and will evaluate virologic and clinical endpoints, with preliminary data expected later this summer. All trials are adaptively designed, and the ultimate numbers of patients enrolled will depend on trial progress and insights from Phase 2 studies.

Recent publication from Regeneron shows that REGN-COV2, greatly reduces virus load in lower and upper airway and decreases virus induced pathological sequalae when administered prophylactically or therapeutically in both rhesus macaques and golden hamsters. The ability of REGN-COV2 to almost completely block detection of sgRNA matches or exceeds the effects recently shown in vaccine efficacy studies.

Status: On September 14, 2020, Regeneron Pharmaceuticals, and the University of Oxford announced that RECOVERY, one of the world’s largest randomized clinical trials of potential COVID-19 treatments, will evaluate Regeneron’s investigational anti-viral antibody cocktail, REGN-COV2. The Phase 3 open-label trial in patients hospitalized with COVID-19 will compare the effects of adding REGN-COV2 to the usual standard-of-care versus standard-of-care on its own. The open-label RECOVERY trial will assess the impact of adding REGN-COV2 to the usual standard-of-care on all-cause mortality 28 days after randomization. Other endpoints include the impact on hospital stay and the need for ventilation. It is anticipated that at least 2,000 patients will be randomly allocated to receive REGN-COV2 plus usual standard-of-care, and results will be compared with at least 2,000 patients who receive standard-of-care on its own. Usual standard-of-care varies by local hospital.

References:

  • Press Release: Phase III COVID-19 Prevention Trial with Antibody Cocktail. Regeneron (07/06/20).
  • Publication: Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science (08/21/20).
  • Publication: Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science (08/21/20).
  • Preprint: REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters. BioRxiv (08/03/20).
  • Press Release: Recovery covid-19 phase 3 trial to evaluate Regeneron’s REGN-COV2 investigational antibody cocktail in the UK. Regeneron (09/14/20).

Candidate: LY3819253 (LY-CoV555)

Developers: Eli Lilly, AbCellera, Shanghai Junshi Bioscience, NIAID

Locations: United States

Clinical Trial IDs: NCT04497987(Phase 2), NCT04507256 (Phase 2)

Description: LY-CoV555 is a potent, neutralizing IgG1 mAb directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19. Emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and tested by the scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. It was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.

On 03 August, 2020 Eli Lilly announced that is moving into a late-stage, Phase III clinical trial for the antibody COVID-19 treatment. Recruitment will come from residents and staff at long-term care facilities in partnership with the National Institute of Allergy and Infectious Diseases (NIAID). First-of-its-kind study will enroll up to 2,400 residents and staff at long-term care facilities; will utilize customized mobile research units to conduct the study on-site.

Status: On September 16, 2020, Interim analysis of the BLAZE-1 clinical trial: Primary endpoint of viral load change from baseline at day 11 was met for one of three doses; consistent effects of viral reduction seen at earlier time points. Rate of hospitalizations and ER visits was 1.7 percent (5/302) for LY-CoV555 versus 6 percent (9/150) for placebo, which corresponds to a 72 percent risk reduction in this limited population. LY-CoV555 was well-tolerated across all doses with no drug-related serious adverse events reported. BLAZE-1 is a randomized, double-blind, placebo-controlled Phase 2 study designed to assess the efficacy and safety of LY-CoV555 and LY-CoV016 for the treatment of symptomatic COVID-19 in the outpatient setting. Across all treatment arms, the trial will enroll an estimated 800 participants.

References:

  • Press Release: Lilly Begins World’s First Study of a Potential COVID-19 Antibody Treatment in Humans. Eli Lilly (06/01/20).
  • Press Release: Lilly Initiates Phase 3 Trial of LY-CoV555 for Prevention of COVID-19 at Long-Term Care Facilities in Partnership with the National Institute of Allergy and Infectious Diseases (NIAID). Eli Lilly (08/03/20).
  • Press Release: Lilly announces proof of concept data for neutralizing antibody LY-CoV555 in the COVID-19 outpatient setting. Eli Lilly (09/16/20).

Candidate: Sarilumab (Kevzara)

Developers: Sanofi, Regeneron Pharmaceuticals

Locations: Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russian Federation, Spain

Clinical Trial IDs: NCT04327388 (Phase III); NCT04386239 (Phase 1)

Description: Kevzara is currently approved in multiple countries to treat adults with moderately to severely active rheumatoid arthritis who have not responded to or tolerated previous therapy. Kevzara is a fully-human mAB that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19 infection. The role of IL-6 is supported by preliminary data from a single-arm study in China using another IL-6 receptor inhibitor.

U.S. Phase 3 trial of Kevzara (sarilumab) 400 mg in COVID-19 patients requiring mechanical ventilation did not meet its primary and key secondary endpoints when Kevzara was added to best supportive care compared to best supportive care alone (placebo). Minor positive trends were observed in the primary pre-specified analysis group (critical patients on Kevzara 400 mg who were mechanically ventilated at baseline) that did not reach statistical significance and these were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline. A separate Sanofi-led trial outside of the U.S. in hospitalized patients with severe and critical COVID-19 using a different dosing regimen is ongoing.

Status: On September 1, Sanofi announced that the global Phase 3 trial investigating intravenously administered Kevzara (sarilumab) at a dose of 200 mg or 400 mg  in severely or critically ill  patients hospitalized with COVID-19 did not meet its primary endpoint and key secondary endpoint when Kevzara was compared to placebo added to usual hospital care. The 420-patient randomized trial was conducted outside the U.S. in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia and Spain (86 in placebo, 161 in 200 mg, and 173 in 400 mg arms).

References:

  • Publication: COVID‐19 pneumonia treated with Sarilumab: A clinical series of eight patients. J Med Virol (06/16/20).
  • Preprint: Sarilumab use in severe SARS-CoV-2 pneumonia. medrxiv (05/18/20).
  • Press Release: Sanofi provides update on Kevzara® (sarilumab) Phase 3 trial in severe and critically ill COVID-19 patients outside the U.S. Sanofi (09/01/20).

Candidate: COVI-GUARD (Neutralizing Antibody – STI 1499) and COVI-SHIELD (Neutralizing Antibody Cocktail)

Developers: Sorrento Therapeutics, Inc.

Locations: United States

Clinical Trial IDs: NCT04454398 (Phase 1)

Description: Sorrento is developing a Neutralizing Antibody COVI-GUARD (Neutralizing Antibody – STI 1499) which binds to S1 subunit of SARS-CoV-2 Spike protein. It is also developing a Neutralizing Antibody Cocktail COVI-SHIELD (Neutralizing Antibody Cocktail)  to bind to distinct epitopes on SARS-CoV-2 Spike protein. The antibody cocktail potentially creates a high barrier to emergence of resistant variants in treated individuals. Both the mAbs Fc regions are engineered to eliminate interactions with host Fc receptors, thereby decreasing risk of Antibody Dependent Enhancement of SARS-CoV-2 infection.

Sorrento Therapeutics is teaming up with New York City-based Mount Sinai Health System to develop COVI-SHIELD to treat COVID-19. COVI-SHIELD is expected to deliver a mixture of three antibodies that combined recognize three specific regions of the SARS-CoV-2 Spike protein.

August 19, 2020, Sorrento announced that it is filing an investigational new drug application (IND) for COVI-GUARD (STI-1499) for hospitalized COVID-19 patients. Sorrento has previously received guidance from the FDA in response to a pre-IND meeting package and believes it has addressed all questions and followed the recommendations from the agency for all sections of the IND. As Sorrento previously announced, in preclinical studies, STI-1499 demonstrated 100% neutralizing effect (in vitro) of the antibody and that a low dose prevented SARS-CoV-2 from infecting healthy cells in such preclinical in vitro studies. Animal data generated by Dr. Paessler’s laboratory at the UTMB in Syrian Golden Hamsters infected with SARS-CoV-2, justify the IND filing and continued clinical development.

The highest proposed dose (200 mg per patient) in the phase 1 safety trial is a much lower dose than currently being tested for other known antibodies in active clinical studies. The potentially higher potency of the antibody may allow for faster scaled manufacturing (availability to patients) and potentially a lower cost per dose as compared to other known antibodies currently being evaluated.

STI-1499 antibody has also been evaluated in preclinical studies against multiple strains of SARS-CoV-2, including the highly contagious D614G mutant, the current dominant strain globally. In such preclinical studies, the antibody has been 100% effective against the highly contagious D614G mutant strain at a low dose.

Status: September 16, 2020, Sorrento announced that phase 1 clinical trial for STI-1499 (COVI-GUARD™) in hospitalized COVID-19 patients has received FDA notice that it may proceed with patient enrollment. The initial trial is expected to enroll rapidly and is expected to be followed by large trials targeting a potential EUA submission as early as before the end of this year. Sorrento has initiated cGMP manufacturing to produce 50,000 doses in anticipation of a potential EUA.

References:

  • Press Release: Sorrento And Mount Sinai Health System To Jointly Develop COVI-SHIELD™ Antibody Therapy Targeting SARS-CoV-2 Infection (COVID-19). Sorrento (05/12/2020).
  • Publication: Sorrento’s antibody completely blocks Covid-19 in-vitro. Pharmaceutical-technology (05/18/20).
  • Press Release: Sorrento Announces FDA IND Filing Today for COVI-GUARD Neutralizing and High Potency Antibody Against SARS-CoV-2. Sorrento (08/19/20).
  • Press Release: Sorrento Receives US FDA Clearance to Proceed With Phase 1 Clinical Trial of STI-1499 (COVI-GUARD) Neutralizing Antibody in COVID-19 Positive Patients. Sorrento (09/16/20).

Updated: 28 September, 2020.

  • Food supplement resveratrol and its structural analog pterostilbene exhibit potent antiviral properties against SARS-CoV-2 in vitro [Link] (09/28/20)
  • High-risk patients receiving ivermectin become SARS-CoV-2 negative faster and were less likely to develop respiratory distress [Link] (09/28/20)
  • FUJIFILM’s anti-influenza drug avigan (Favipiravir) tablet meets primary endpoint in phase 3 clinical trial in Japan [Link] (09/28/20)
  • No significant difference in viral clearance was seen between early and late treatments with the anti-viral agent favipiravir [Link] (09/28/20)
  • Twenty approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles, identified in throughput screening [Link] (09/21/20)
  • Investigational drug Brilacidin, a polymer-based antibiotic, shows synergistic inhibition of SARS-CoV-2 when used in combination with Remdesivir [Link] (09/21/20)
  • Docking study shows that ivermectin performed better than lopinavir and simeprevir as an RNA-dependent RNA polymerase inhibitor [Link] (09/15/20)
  • Colchicine treatment leads to clinical benefits in a single-center propensity score matched cohort study [Link] (09/15/20)
  • JAK inhibitor baricitinib in combination with remdesivir reduces time to recovery in hospitalized COVID-19 patients [Link] (09/14/20)
  • Coronavirus 3CL protease inhibitor PF-07304814 exhibits potent in vitro antiviral activity against SARS-CoV-2 and exhibits synergism with remdesivir [Link] (09/14/20)
  • Tizoxanide, a metabolite of the existing antiviral Nitazoxanide, shows SARS-CoV-2 inhibitory effect in vitro by lowering cell metabolism and RNA processing and modification [Link] (09/07/20)
  • Known antiviral drugs, Boceprevir and GC376, inhibit SARS-CoV-2 by targeting its Mpro protease [Link] (09/04/20)

Select strategies are detailed in the section below:

There are no FDA-approved drugs for the treatment of COVID-19, although remdesivir, an investigational antiviral drug, is available through an FDA emergency use authorization. Definitive clinical trial data are needed to identify safe and effective treatments for COVID-19. COVID-19 Treatment Guidelines Panel provides recommendations on using antiviral drugs to treat COVID-19 based on the available data.

  • Remdesivir – For patients who do not require oxygen delivery through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO – The Panel recommends using remdesivir for 5 days or until hospital discharge, whichever comes first
  • The Panel recommends against the use of chloroquine or hydroxychloroquine or use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19, except in a clinical trial.
  • The Panel recommends against using combination of hydroxychloroquine plus azithromycin, because of the potential for toxicities.
  • The Panel recommends against using Lopinavir/ritonavir or other HIV protease inhibitors, because of unfavorable pharmacodynamics and because clinical trials have not demonstrated a clinical benefit.
  • The Panel recommends against the use of ivermectin for the treatment of COVID-19, except in a clinical trial

References:

  • NIH: Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19 (Accessed 09/21/20).

Candidate: Remdesivir (Veklury, GS-5734)

Sponsors/Developers: Gilead Sciences, Inc.

Location: United States

Clinical Trial IDs: NCT04501952 (Outpatient Setting, Phase 3), NCT04431453 (CARAVAN, < 18 Years, Phase 2/3), NCT04292899 (Severe COVID-19, Phase 3), NCT04292730 (Moderate COVID-19, Phase 3), NCT04323761 (expanded access)

Description: The broad-spectrum antiviral agent Remdesivir (GS-5734; Gilead Sciences, Inc) is a nucleotide analog prodrug. The US FDA issued EUA of remdesivir to allow emergency use in children and hospitalized adults. The findings from the NIAID trial of remdesivir in hospitalized patients with advanced COVID-19 have been published in a peer-reviewed medical journal. These findings support the use of remdesivir in this population, with the largest benefit observed among individuals who required oxygen supplementation but were not mechanically ventilated. The open-label phase 3 SIMPLE trial (n = 397) in hospitalized patients with severe COVID-19 disease not requiring mechanical ventilation showed similar improvement in clinical status with the 5-day remdesivir regimen compared with the 10-day regimen on day 14 (OR=0.75). The first published report concerning remdesivir compassionate use described clinical improvement in 36 of 53 hospitalized patients (68%) with severe COVID-19. At baseline, 30 patients (57%) were receiving ventilation and 4 (8%) extracorporeal membrane oxygenation (ECMO).

Coordinating closely with the U.S. FDA, Gilead has designed and will soon begin enrollment of an open-label, single-arm Phase 2/3 clinical trial that will evaluate the safety, tolerability, pharmacokinetics and efficacy of remdesivir in treating approximately 50 pediatric patients with moderate-to-severe COVID-19, including newborns through adolescents. This important trial will be conducted at more than 30 sites in the United States and Europe (Trial ID: NCT04431453).

On July 10, 2020 Gilead presented additional data -Remdesivir was associated with an improvement in clinical recovery and a 62% reduction in the risk of mortality compared with standard of care – an important finding that requires confirmation in prospective clinical trials. Traditionally marginalized racial/ethnic groups treated with Remdesivir had similar clinical outcomes as overall patient population. Compassionate use program, which demonstrated that 83% of pediatric patients (n=77) and 92% of pregnant and postpartum women (n=86) with a broad spectrum of disease severity recovered by Day 28. To further the understanding of these results in individual patient cases, Gilead recently announced the initiation of a global, open-label Phase 2/3 trial to evaluate the safety, tolerability and pharmacokinetics of remdesivir in pediatric patients from birth to less than 18 years of age. Gilead is also collaborating on a study for pregnant women.

Status: Gilead announced on 28 August that the U.S. FDA expanded the Emergency Use Authorization (EUA) enabling use of the investigational antiviral Veklury (remdesivir) to treat all hospitalized patients with COVID-19, in addition to the previous authorization for patients hospitalized with severe COVID-19. The expanded EUA is based on results from the Phase 3 SIMPLE trial evaluating Veklury in hospitalized patients with moderate COVID-19 pneumonia, as well as results from the National Institute of Allergy and Infectious Diseases (NIAID) ACTT-1 trial in hospitalized patients with a range of disease severity.

References:

  • Publication: Remdesivir for the Treatment of Covid-19 – Preliminary Report. NEJM (05/22/20).
  • Publication: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. NEJM (05/27/20).
  • Publication: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature (06/09/20).
  • Publication: Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science (06/26/20).
  • Publication: Compassionate Use of Remdesivir for Patients with Severe Covid-19. NEJM (06/11/20).
  • Press Release: Gilead Presents Additional Data on Investigational Antiviral Remdesivir for the Treatment of COVID-19. Gilead (07/10/20).
  • Press Release: Gilead’s Investigational Antiviral Veklury® (Remdesivir) Receives U.S. Food and Drug Administration Emergency Use Authorization for the Treatment of Patients With Moderate COVID-19. Gilead (08/28/20).

Favipiravir is an oral antiviral approved for the treatment of influenza in Japan. It selectively inhibits RNA polymerase, which is necessary for viral replication. Japan has commenced with a phase 3 clinical trial. In the United States, a phase 2 trial will enroll approximately 50 patients with COVID-19, in collaboration with Brigham and Women’s Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. In India, a phase 3 trial combining 2 antiviral agents, favipiravir and umifenovir, started in May 2020.

Publications:

  • Fujifilm announces the start of a phase III clinical trial of influenza antiviral drug “Avigan Tablet” on COVID-19 and commits to increasing production [Link] (31-Mar-20).
  • Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection. [Link] (05-Apr-20).
  • Glenmark initiates Phase 3 clinical trials on antiviral Favipiravir for COVID-19 patients in India [Link] (12-May-20).
  • Appili Therapeutics Submits CTA with Health Canada to Sponsor Prophylactic Phase 2 Clinical Trial Evaluating FUJIFILM Toyama Chemical’s Favipiravir as a Preventative Measure Against COVID-19 in Canadian Long-Term Care Facilities [Link] (12-May-20).
  • Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase [Link] (15-May-20).
  • Health Canada Clears Appili Therapeutics’ Phase 2 Clinical Trial Evaluating Favipiravir as a Prophylactic Agent [Link] (21-May-20).
  • Glenmark starts Phase III Favipiravir combination study [Link] (26-May-20).
  • Glenmark says restricted use of favipiravir approved in India for COVID-19 patients [Link] (19-Jun-20).
  • Real-world Experience with Favipiravir for Treatment of COVID-19 in Thailand: Results from a Multi-center Observational Study [Link] (01-Jul-20).
  • Stanford Medicine trial to test favipiravir for treating COVID-19 outpatients [Link] (01-Jul-20).
  • Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with Covid-19: a case series [Link] (03-Jul-20).

This drug was created by scientists at a nonprofit biotech company owned by Emory University. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC prodrug (beta-D-N4-hydroxycytidine-5′-isopropyl ester), improved pulmonary function and reduced virus titer and body weight loss. Unlike remdesivir, EIDD-2801 can be taken orally, which would make it available to a larger number of people. The potency of NHC/EIDD-2801 against multiple CoVs and oral bioavailability highlights its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic CoVs. Ridgeback Biotherapeutics announced the launch of two Phase 2 clinical trials to test the efficacy of EIDD-2801 as an anti-viral treatment for COVID-19. Phase 1 trials recently determined that EIDD-2801 is safe in human doses that provide blood levels well above levels that animal models suggest should be effective against SARS-CoV-2, the virus which causes COVID-19. EIDD-2801 will be administered to patients 18 years old and over in two studies

Publications:

  • An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice [Link] (29 April 2020).
  • FDA Clears the Way for Ridgeback Biotherapeutics to begin Human Testing of a Promising Potential Treatment for COVID-19 [Link] (06 April 2020).
  • An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice [Link] (06 April 2020).
  • Ridgeback Biotherapeutics LP: Orally available antiviral compound, EIDD-2801, to begin human testing (Commenced Phase 1 on April 10th) [Link] (13 April 2020).
  • Merck and Co., Inc. Takes 3 Major Shots at COVID-19: Themis, IAVI and Ridgeback Bio [Link] (26 May 2020).
  • Ridgeback Biotherapeutics Announces Launch of Phase 2 Trials Testing EIDD-2801 as Potential Treatment  [Link] (19 June 2020).

Ivermectin is an FDA-approved broad spectrum anti-parasitic agent that in recent years has shown to have anti-viral activity against a broad range of viruses. Ivermectin has an established safety profile for human use.

Ivermectin inhibits the replication of SARS-CoV-2 in vitro as per a recent study. A single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. There have been further preprints published discussing potency of the drug.

Publications:

  • The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro [Link] (03 April 2020).
  • Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view [Link] (17 April 2020).
  • The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19 [Link] (26 April 2020).
  • ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19 [Link] (09 June 2020).
  • Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen [Link] (12 June 2020).
  • Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial) [Link] (08 July 2020).

This is a combination of two drugs – lopinavir and ritonavir – that works against HIV-1. Lopinavir/ritonavir is an inhibitor of SARS-CoV 3CLpro in vitro, and this protease appears highly conserved in SARS-CoV-2. Based on in vitro testing and previous clinical trials demonstrating its efficacy against other coronaviruses, LPV/r was regarded as an option for treating COVID-19. It is thought to have a poor selectivity index, indicating that higher than tolerable levels of the drug might be required to achieve meaningful inhibition in vivo.

The CDC/NIH Panel recommends against the use of lopinavir/ritonavir (AI) or other HIV protease inhibitors (AIII) for the treatment of COVID-19, except in the context of a clinical trial. The pharmacodynamics of HIV protease inhibitors raise concern regarding whether drug levels adequate to inhibit the SARS-CoV-2 protease can be achieved with oral dosing. In a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, no benefit was observed with lopinavir–ritonavir treatment beyond standard care (Chinese Clinical Trial Register number, ChiCTR2000029308)

Publications:

  • Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial [Link] (08-May-20).
  • AbbVie Partnering with Global Authorities to Determine Efficacy of HIV Drug in Treating COVID-19 [Link] (09-Mar-20).
  • An exploratory randomized controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI) [Link] (15-Apr-20).
  • Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial [Link] (04-May-20).
  • A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19 [Link] (7-May-20).
  • DISCOVERY clinical trial updates [Link] (14-May-20).
  • Lopinavir/ritonavir is associated with pneumonia resolution in COVID‐19 patients with influenza coinfection: a retrospective matched‐pair cohort study [Link] (04-Jul-20).

The drugs inhibit the 3CLpro enzyme of SARS-CoV-2 and possibly also inhibition of the PLpro enzyme. In an in vitro study, darunavir did not show activity against SARS-CoV-2. Also, results from an unpublished randomized controlled trial of 30 patients in China showed that darunavir/cobicistat was not effective in the treatment of COVID-19.

Publications:

  • Lack of antiviral activity of darunavir against SARS-CoV-2 [Preprint] (08 April, 2020).
  • Johnson & Johnson. Lack of evidence to support use of darunavir-based treatments for SARS-CoV-2 [Link] (May 11, 2020).

Developed by ViralClear Pharmaceuticals Inc., it has shown previously to have antiviral and immune-suppressing effects. The company is running a phase II trial of this drug. People with advanced COVID-19 will be randomized to receive either merimepodib with remdesivir, or remdesivir plus a placebo (NCT04410354).

Publications:

  • Positive Data Generated by BioSig Subsidiary ViralClear on COVID-19 [Link] (09-Apr-20).
  • Mayo Clinic preparing to Commence Phase II FDA clinical trial for the treatment of COVID-19 with Vicromax [Link] (16-Apr-20).
  • ViralClear Publishes in F1000 Research In Vitro Data Demonstrating Synergy between Merimepodib and Remdesivir Against SARS-CoV-2 [Link] (14-May-20).

Updated: 28 September, 2020.

  • Famotidine shows no benefits compared to PPI or hydroxychloroquine users among hospitalized patients [Link] (09/28/20)
  • Human recombinant soluble ACE2 successfully used in a patient with severe COVID-19 [Link] (09/28/20)
  • Receiving methyl-prednisolone pulses was associated with lower risk of death or intubation in 242 patients with severe COVID-19 pneumonia  [Link] (09/28/20)
  • Long-term hydroxychloroquine usage did not prevent SARS-CoV-2 infection in patients with existing rheumatological conditions [Link] (09/28/20)
  • Convalescent plasma therapy shows benefits in 17 B-cell depleted patients with protracted COVID-19 disease [Link] (09/28/20)
  • Therapeutic enoxaparin improved gas exchange relative to standard anticoagulant thromboprophylaxis and reduced the need for mechanical ventilation [Link] (09/28/20)
  • Randomized clinical trial in Chile with 57 patients shows no benefit in the primary outcome for convalescent plasma therapy [Link] (09/21/20)
  • Meta-analysis of 7,913 patients from 26 randomized trials finds no mortality benefit to hydroxychloroquine or chloroquine [Link] (09/21/20)
  • Corticosteroid treatment was not associated with intubation or death among patients with COVID-19 pneumonia in an observational study [Link] (09/21/20)
  • Intravenous methylprednisolone pulse improves clinical outcomes in patients with severe disease [Link] (09/21/20)
  • Rheumatoid arthritis drug baricitinib resolves lower airway inflammation and neutrophil in infected animal models without affecting viral shedding [Link] (09/21/20)
  • Investigational drug Brilacidin, a polymer-based antibiotic, shows synergistic inhibition of SARS-CoV-2 when used in combination with Remdesivir [Link] (09/21/20)
  • Combination of four affordable drugs (ivermectin, dexamethasone, enoxaparin and aspirin) was effective in preventing progression in mild cases and decreasing mortality in all patients [Link] (09/21/20)
  • Histamine receptor blockade with cetirizine and famotidine reduces mortality and symptom progression [Link] (09/15/20)
  • Convalescent plasma therapy was effective in 39 patients with severe or life-threatening COVID-19 [Link] (09/15/20)
  • Ambroxol hydrochloride inhibits SARS-CoV-2 infection by modulating interaction between SARS-CoV-2 spike and human ACE2 [Link] (09/15/20)
  • JAK inhibitor baricitinib in combination with remdesivir reduces time to recovery in hospitalized COVID-19 patients [Link] (09/14/20)
  • Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) fails in COVID-19 patients with lymphopenia [Link] (09/14/20)
  • Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) fails in COVID-19 patients with lymphopenia [Link] (09/14/20)
  • Prospective cohort study in Saudi Arabia with 7,892 symptomatic mild to moderate COVID-19 patients reports benefits of early intervention with Hydroxychloroquine [Link] (09/14/20)
  • Therapeutic doses of nitric oxide inhibit viral replication in VERO E6 cells with no cytotoxic impact [Link] (09/11/20)
  • Adding azithromycin to standard of care treatment did not improve clinical outcomes in a trial of 447 patients with severe disease [Link] (09/10/20)
  • Multicenter, randomized controlled phase 2 trial of convalescent plasma therapy in moderately ill patients from 39 hospitals shows no reduction in mortality or progression [Link] (09/10/20)
  • Far-ultraviolet light (222-nm) is effective against SARS-CoV-2 contamination in vitro [Link] (09/10/20)
  • CoDEX randomized clinical trial for dexamethasone reports increased benefits over standard care in 299 patients with moderate or severe disease [Link] (09/07/20)
  • Convalescent plasma therapy was beneficial in a multicenter study of 80 patients with severe COVID-19 pneumonia [Link] (09/07/20)
  • Decoy receptors, like a soluble version of the ACE2 receptor designed using ACE2 mutants, can bind with high affinity to Spike protein and prevent viral escape [Link] (09/04/20)
  • Convalescent plasma administered early in the disease course shows better benefits than later in disease progression [Link] (09/02/20)
  • Calcifediol reduces disease severity and need for ICU admission [Link] (09/02/20)
  • Corticosteroids boost response in severe COVID-19 patients receiving tocilizumab [Link] (09/02/20)
  • Early administration of convalescent plasma reduced mortality and was safe in a Mayo Clinic study of 20,000 hospitalized patients [Link] (09/01/20)
  • Lithium carbonate significantly reduces disease markers and improves immune response in an observational study of six patients [Link] (09/01/20)
  • Heparin can inhibit SARS-CoV-2 infection in vitro [Link] (09/01/20)

Select strategies are detailed in the section below:

Candidate: OLUMIANT (Baricitinib, LY3009104).

Developers: Eli Lilly, Incyte, National Institute of Allergy and Infectious Diseases (NIAID), Emory University.

Clinical Trial Ids: COV/BARRIER/NCT04421027 (Phase 3), ACTT-2/NCT04401579 (Phase 3)

Locations: USA, UK, Argentina, Brazil and others.

Description: Many patients with severe respiratory disease due to COVID-19 have features consistent with cytokine release syndrome. Due to increased activation of the JAK/STAT pathway, it is postulated that JAK-inhibitors might have a useful role in treating these patients.

OLUMIANT is a once-daily, oral JAK inhibitor approved in the U.S. for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF inhibitor therapies, and approved outside of the U.S. for patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases. OLUMIANT has greater inhibitory potency at JAK1, JAK2 and TYK2 relative to JAK3; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

Status: Lilly and Incyte announced on September 14, initial data emerging from the Adaptive COVID-19 Treatment Trial (ACTT-2) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). ACTT-2 included more than 1,000 patients and began on May 8 to assess the efficacy and safety of a 4-mg dose of baricitinib plus remdesivir versus remdesivir in hospitalized patients with COVID-19. Baricitinib in combination with remdesivir met the primary endpoint of reduction of time to recovery in comparison with remdesivir. Study investigators noted an approximately one-day reduction in median recovery time for the overall patient population treated with baricitinib in combination with remdesivir versus those treated with remdesivir. This finding was statistically significant. The study also met a key secondary endpoint comparing patient outcomes at Day 15 using an ordinal 8-point scale ranging from fully recovered to death.

Lilly will review the ACTT-2 data with NIAID and assess any impact on COV-BARRIER, the Phase 3 randomized, double-blind, placebo-controlled study it initiated in June to evaluate the efficacy and safety of baricitinib versus background therapy in hospitalized adults with COVID-19.

A preprint from Emory University showed investigation of the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib.

References:

  • Press Release: Baricitinib in Combination with Remdesivir Reduces Time to Recovery in Hospitalized Patients with COVID-19 in NIAID-Sponsored ACTT-2 Trial. Eli Lilly (09/14/20).
  • Press Release: Lilly Begins a Phase 3 Clinical Trial with Baricitinib for Hospitalized COVID-19 Patients. Eli Lilly (06/15/20).
  • Preprint: Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. bioRxiv (09/16/20).

Candidate: Low-dose Dexamethasone.

Clinical Trial IDs: ISRCTN50189673 (Phase II/III), EudraCT 2020-001113-21 (Phase II/III), NCT04381936 (Phase II/III).

Locations: United Kingdom.

Developers: Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial- This trial is supported by a grant to the University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome,  the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, and NIHR Clinical Trials Unit Support Funding.

Description: In March 2020, the RECOVERY trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK. On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomized to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomized to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%). Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).

Status: In a prospective meta-analysis of 7 randomized trials that included 1703 patients of whom 647 died (including the RECOVERY trial), 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo (summary odds ratio, 0.66).

On the basis of the preliminary report from the RECOVERY trial, the COVID-19 Treatment Guidelines Panel recommends using dexamethasone 6 mg per day for up to 10 days or until hospital discharge, whichever comes first, for the treatment of COVID-19 in hospitalized patients who are mechanically ventilated and in hospitalized patients who require supplemental oxygen but who are not mechanically ventilated. If dexamethasone is not available, the Panel recommends using alternative glucocorticoids such as prednisonemethylprednisolone, or hydrocortisone.

References:

  • News: Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. Recovery Trial (06/16/20).
  • Preprint: Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report. medRxiv (06/22/20).
  • Publication: Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. NEJM (07/17/20).
  • Meta-analysis: Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19. JAMA (09/02/20).
  • RECOVERY Trial: Website for Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial, as accessed on 09/21/20.
  • NIH: Guidelines and recommendations for Dexamethasone, as accessed on 09/21/20.

FDA has issued guidance to provide recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency.

Convalescent plasma that contains antibodies to SARS-CoV-2 is being studied for administration to patients with COVID-19. Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2003 SARS-CoV-1 epidemic, the 2009-2010 H1N1 influenza virus pandemic, and the 2012 MERS-CoV epidemic.

Although promising, convalescent plasma has not yet been shown to be safe and effective as a treatment for COVID-19. Therefore, it is important to study the safety and efficacy of COVID-19 convalescent plasma in clinical trials.

On August 23, 2020, the FDA issued an Emergency Use Authorization (EUA) for COVID-19 convalescent plasma for the treatment of hospitalized patients. The COVID-19 Treatment Guidelines Panel (the Panel) reviewed the available evidence from published and unpublished data on convalescent plasma for the treatment for COVID-19, including the FDA analyses that supported the EUA.

The FDA analysis of data on a subset of hospitalized patients from the Mayo Clinic’s Expanded Access Program (EAP) compared outcomes in patients who received convalescent plasma with high titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies to outcomes in patients who received plasma with low titers and found no difference in 7-day survival overall. Among patients who were not intubated, 11% of those who received convalescent plasma with high antibody titers died within 7 days of transfusion compared with 14% of those who received convalescent plasma with low antibody titers. Among those who were intubated, there was no difference in 7-day survival. Although these data suggest that convalescent plasma with high antibody titers may be beneficial in nonintubated patients, uncertainty remains about the efficacy and safety of convalescent plasma due to the lack of a randomized control group and possible confounding in the Mayo Clinic’s EAP. Additionally, antibody levels in currently available COVID-19 convalescent plasma are highly variable, and assays to determine the effective antibody titers remain limited.

Based on the available evidence, the Panel has determined the following:

  • There are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19.
  • Available data suggest that serious adverse reactions following the administration of COVID-19 convalescent plasma are infrequent and consistent with the risks associated with plasma infusions for other indications. The long-term risks of treatment with COVID-19 convalescent plasma and whether its use attenuates the immune response to SARS-CoV-2, making patients more susceptible to reinfection, have not been evaluated.
  • Convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19.
  • Prospective, well-controlled, adequately powered randomized trials are needed to determine whether convalescent plasma is effective and safe for the treatment of COVID-19. Members of the public and health care providers are encouraged to participate in these prospective clinical trials.

References:

  • CONCOVID Preprint: Convalescent Plasma for COVID-19. A randomized clinical trial (NCT04342182). medRxiv (07/03/20).
  • Publication: Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial (ChiCTR2000029757). JAMA (06/03/20).
  • Mayo Clinic Preprint: Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients. medRxiv 05/14/20).
  • News: FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment. FDA (08/23/20).
  • FDA guidance: Recommendations for Investigational COVID-19 Convalescent Plasma (09/01/20).
  • Mayo Clinic: Safety Update – COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients (09/01/20).

Updated: 28 September, 2020.

The table lists various ongoing efforts (Treatments and Vaccines) from developers and sponsors globally to identify a safe and efficacious solution to the pandemic. Data is collated from various sources including WHO and Milken Institute trackers.

Updated: September 11, 2020.

COVID-19 Clinical Trials: An Overview

Researchers and clinicians all over the world have reacted to the COVID-19 pandemic and the ensuing public health crisis with a colossal worldwide effort to discover a treatment. With increasing number of global cases and fatalities, the world waits for positive results from these ongoing trials. Several existing antivirals, traditional and alternative medicines, investigative or repurposed compounds, support devices as well as procedures, supplements are being explored in the context of SARS-CoV-2 infection.

The pandemic has changed the way trials are being conducted, with several radical changes in terms of recruitment, obtaining consent remotely, telemedical monitoring and implementation of more innovative trial designs. There is a need to make these positive changes instigated by the pandemic sustainable [1].

The World Health Organization’s International Clinical Trials Registry Platform (WHO ICTRP) ensures that “a complete view of research is accessible to all those involved in health care decision making”. Information in the WHO ICTRP comprises of structured data from several major clinical trial databases from countries or regions of the world, including but not limited to the ClinicalTrials.gov [2], Chinese Clinical Trial Registry (ChiCTR) [3], The Clinical Trials Registry- India (CTRI) [4], Iranian Registry of Clinical Trials [5], European Union Clinical Trials Register [6] and the ISRCTN register [7].

As on September 10, 2020, there are 5650 trials registered in the WHO ICRTRP database for COVID-19, with 3308 Interventional trials and rest comprising majorly of Observational studies (2233), Diagnosis tests (45), and others [8].

Of note, is the SOLIDARITY trial [9]. Solidarity is an international clinical trial to help find an effective treatment for COVID-19, launched by the WHO and partners. The Solidarity Trial tests various options against standard of care to assess their  effectiveness against COVID-19. Based on evidence from laboratory, animal and clinical studies, the following treatment options were selected – Remdesivir, Lopinavir/Ritonavir, Lopinavir/Ritonavir with Interferon beta-1a, Chloroquine or Hydroxychloroquine. Other drugs can be added based on emerging evidence.

The US FDA has created a special emergency program for possible coronavirus therapies, the Coronavirus Treatment Acceleration Program (CTAP). As per the program guidelines, it aims to use every available method to move new treatments to patients as quickly as possible, while at the same time finding out whether they are helpful or harmful [10]. The CTAP Dashboard provides users with a snapshot of development of potential COVID-19 therapeutics. As of August 31, 2020, of the 590+ available therapies, CTAP has reviewed over 300 trials with 5 of the treatments approved for Emergency Use. None of the therapies have been FDA approved so far (Figure 1).

Figure 1: Treatments reviewed by CTAP – Numbers correspond to number of safe to proceed INDs. Excludes INDs related to vaccines (Source: CTAP dashboard [10]). There were 70+ early stage trials and over 240 late stage (Phase 2-4) trials from U. S. included in the analysis.

As per FDA classification, the categories in this bar chart span several categories –

  • Antiviral drugs keep viruses from multiplying and are used to treat many viral infections (such as HIV, Herpes, Hepatitis C, and influenza). 
  • Immunomodulators are aimed at tamping down the body’s own immune reaction to the virus, in cases where the body’s reaction basically goes overboard and starts attacking the patient’s own organs.
  • Neutralizing antibody therapies may help individuals fight the virus and include manufactured antibodies, animal-sourced antibody therapies, and blood-derived products such as convalescent plasma and hyperimmune globulin, which contain antibodies taken from people who have previously had COVID-19.
  • Cell therapy products include cellular immunotherapies and other types of both autologous and allogeneic cells, such as stem cells, and related products.
  • Gene therapy products seek to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership [11] was announced on April 17, 2020 by  National Institutes of Health (NIH), with coordination by the Foundation for the National Institutes of Health (FNIH) involving a collaboration among government and industry partners, including FDA, to prioritize vaccine and therapeutic candidates, streamline clinical trials, and rapidly expand the clinical research resources focused on developing therapies [12]. ACTIV continues to grow and now involves several academic and industry partners (20 biopharmaceutical companies), and up to 8 different government agencies. ACTIV also works closely with other COVID-19 efforts, including FDA and BARDA’s Medical Countermeasures Task Force, the Bill & Melinda Gates Foundation, the Wellcome Trust, the European Commission, the UK government, and the World Health Organization.

The TrialsTracker project dashboard [13] classifies over 5000 trials based on strategies tested against COVID-19. Analysis of major categories highlights the top treatments being investigated world-wide as shown in Figure 2.

Figure 2: A comparison of treatments as a measure of trials they are part of, as on 11 September 2020. Data was obtained from WHO ICTRP [8 ]and the TrialsTracker project [13].

Ever since the first clinical trial was registered early this year, trial registrations have seen an unprecedented pace. The number of registrations on a daily basis since early January 2020 is shown in Figure 3.

Figure 3: The pandemic pace of clinical trial registrations on leading platforms, as per data obtained from WHO ICTRP [8] on 01 September 2020.

For a routinely updated list of all clinical trials with details and links to the registry page, please visit the adjacent tab “List of Clinical Trials”.

Last Updated: September 11, 2020.

References:

  1. Gaba, P., Bhatt, D.L. The COVID-19 pandemic: a catalyst to improve clinical trials. Nat Rev Cardiol (2020). https://doi.org/10.1038/s41569-020-00439-7
  2. ClinicalTrials.gov Registry. https://clinicaltrials.gov/
  3. Chinese Clinical Trial Registry (ChiCTR). http://www.chictr.org.cn/abouten.aspx
  4. The Clinical Trials Registry- India (CTRI). http://ctri.nic.in/Clinicaltrials/login.php
  5. Iranian Registry of Clinical Trials. https://www.irct.ir/
  6. European Union Clinical Trials Register. https://www.clinicaltrialsregister.eu/ctr-search/search
  7. ISRCTN register. https://www.isrctn.com/
  8. World Health Organization’s International Clinical Trials Registry Platform (WHO ICTRP). https://www.who.int/ictrp/en/
  9. “Solidarity” clinical trial for COVID-19 treatments. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments
  10. Coronavirus Treatment Acceleration Program (CTAP) | FDA. https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap
  11. ACCELERATING COVID-19 THERAPEUTIC INTERVENTIONS AND VACCINES (ACTIV). https://www.nih.gov/research-training/medical-research-initiatives/activ
  12. NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options. https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options
  13. The TrialsTracker project dashboard. http://covid19.trialstracker.net/

COVID-19 Global Funding Response

The world is facing an unprecedented challenge with communities and economies everywhere affected by the growing COVID-19 pandemic. IMF estimates suggest that, for each month the pandemic persists, $500 billion is lost from the global economy. The world is coming together to combat the COVID-19 pandemic bringing together governments, organizations and individuals from across industries and sectors to help respond to this global outbreak. The outpour of global solidarity and support sparked by this shared challenge has been phenomenal.

An analysis of data available on the Devex funding database reveals over $20.4 trillion committed to the COVID-19 response to date. Since the beginning of 2020, governments, bilateral and multilateral donors, development banks, philanthropic organizations, and the private sector have all played a role in contributing money, equipment, expertise, and more. As of Aug. 30, 2020, investments totaling $151.4 billion have been made through 663 program announcements and 617 grants have supported $1.7 billion worth of investment. As for business opportunities, 1,157 tenders have seen $3.9 billion invested through program delivery and service partners, while 721 contracts have delivered $763.4 million on the ground.

The WHO Strategic Preparedness and Response Plan outlines a funding need of at least US$675 million for critical response efforts in countries most in need of help through April 2020. People and organizations who want to help fight the pandemic and support WHO and partners can now donate through the COVID-Solidarity Response Fund for WHO at www.COVID19ResponseFund.org. Up to US$224 million has already been raised as of 04 September, 2020 from more than 567,000 individuals, companies and philanthropies.

An overview of how the COVID-19 Solidarity Response Fund is being utlized in response to the pandemic.

The Coalition for Epidemic Preparedness Innovations (CEPI) is a global alliance financing and coordinating the development of vaccines against emerging infectious diseases. CEPI has received support from founding member Norway (US$210 million), UK government (US$270 million), Government of Belgium (US$5.5 million), Government of Canada (US$28.2 million), Greece (US$1.6 million) and German Government’s Federal Ministry (US$157 million).

CEPI, alongside Gavi and the World Health Organisation, launched COVAX – the vaccines pillar of the ACT Accelerator – with the aim of ending the acute phase of the pandemic by the end of 2021. COVAX is the solution that will deliver fair, equitable access to vaccines for every country that participates. Together the aim is to produce 2 billion doses of vaccine and distribute them globally and fairly in 2021. To support the vaccine R&D that is critical to achieving this goal, CEPI estimates that it needs $2.1bn to progress three vaccines to licensure, which will be made available to the world through COVAX. Through COVAX, the risks and benefits of developing and producing vaccines are shared across countries. COVAX works by pooling financial resources to develop vaccines, purchase them at scale, and investing up-front in manufacturing so that vaccines are ready to be distributed as soon as they are licensed. Countries participating in COVAX can access CEPI’s portfolio of COVID-19 vaccine candidates – the largest in the world – which is managed by CEPI’s R&D experts.

To date, CEPI has secured financial support from the Bill & Melinda Gates Foundation,  Wellcome Trust, the European Commission, and the governments of Australia, Belgium, Canada, Denmark, Ethiopia, Germany, Japan, Mexico, Norway and the United Kingdom. In response to call the Governments of Austria, Australia, Belgium, Canada, European Commission, Finland, France, Greece, Germany, Iceland, Italy, Japan, Luxembourg, Kingdom of Saudi Arabia, Norway, the Netherlands, New Zealand, Serbia, Spain, Switzerland, and the United Kingdom, alongside private sector companies and donations through the UN Foundation COVID-19 Solidarity Response Fund, have pledged $1.4 billion in financial contributions.

Through the Bill and Melinda Gates Foundation, the Microsoft founder and philanthropist plan to help fund factories for promising vaccines, even before seeing conclusive data. The foundation has committed more than $350 million to support the global response to COVID-19. This includes $100 million to Gavi’s new COVID-19 Vaccine Advance Market Commitment, to support its future efforts to deliver COVID-19 vaccines to lower-income countries. In addition to the more than $350 million committed, the foundation will also leverage a portion of its Strategic Investment Fund, which addresses market failures and helps make it attractive for private enterprise to develop affordable and accessible health products. For example, the foundation is collaborating with Gavi and the Serum Institute of India to accelerate the manufacture and delivery of up to 100 million doses of COVID-19 vaccines for low- and middle-income countries. $150 million came from the Strategic Investment Fund. The Gates Foundation, along with Wellcome and Mastercard, are the founding funders of the COVID-19 Therapeutics Accelerator. The Accelerator is intended to play a catalytic role by accelerating and evaluating new and repurposed drugs to respond to COVID-19 in the immediate term, and other viruses in the longer-term – up to $50 million of the commitment will go towards supporting the COVID-19 Therapeutics Accelerator.

Biomedical Advanced Research and Development Authority (BARDA) part of the HHS Office of the Assistant Secretary for Preparedness and Response, was established to aid in securing our nation from chemical, biological, radiological, and nuclear (CBRN) threats, as well as from pandemic influenza (PI) and emerging infectious diseases (EID). BARDA supports the transition of medical countermeasures such as vaccines, drugs, and diagnostics from research through advanced development towards consideration for approval by the FDA and inclusion into the Strategic National Stockpile. BARDA has updated its Broad Agency Announcements (BAAs) to focus exclusively on addressing the COVID-19 threat. BARDA’s annual budget of $512 Million has been supplemented by an additional $3.5 billion through the recently passed Coronavirus Aid, Relief, and Economic Security (CARES) Act. The additional funding is allocated for necessary expenses of manufacturing, production, and purchase of various supplies and services. AstraZeneca recently received $1B in BARDA funding to advance vaccine. Another leading candidate, Moderna received $483 million BARDA award for vaccine development, while it awarded $450 million to Janssen Pharmaceuticals, a division of Johnson & Johnson, to develop a vaccine.

On 4 May 2020, the EU and its partners hosted an international pledging conference which has now raised €9.8 billion in pledges from donors worldwide to kick-start the global cooperation. This includes a pledge of €1.4 billion from the Commission of which €1 billion comes from Horizon 2020. The EU plays a central role is supporting and coordinating research on infectious diseases, with €4.1 billion invested from 2007 to 2019 through the 7th Framework Programme and Horizon 2020, which foresees further commitments in 2020 in addition to the €1 billion pledge for coronavirus research. This has included initiatives to coordinate European efforts to address antimicrobial resistance, as well as preparedness and emergency response to outbreaks (Ebola, Zika). From the Horizon 2020, €620 million has already been mobilised, and a further €394 million has been pledged.

The Board of Directors of the European Investment Bank (EIB) has agreed on the structure and business approach of the Pan-European Guarantee Fund (EGF) to tackle the economic consequences of the COVID-19 pandemic. The Fund was endorsed by the European Council as part of the overall EU COVID-19 response package. It will enable the EIB Group to scale up its support for mostly small and medium-sized European companies, providing up to €200 billion of additional financing.

The Global Fund, the largest multilateral funder of health systems worldwide, is providing immediate funding of up to US$1 billion to help countries fight COVID-19, mitigate the impacts on lifesaving HIV, TB and malaria programs, and prevent fragile health systems from being overwhelmed. Under the World Health Organization’s leadership, the Global Fund is using its experience working with partners and governments in more than 100 countries to coordinate our response on a massive global scale.

Multiple National Institutes of Health (NIH) Institutes have issued a Notice of Special Interest (NOSI) to provide funding for research topics related to COVID-19. National Institute on Aging (NIA), National Institute of Mental Health (NIMH), The National Heart, Lung, Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of General Medical Sciences (NIGMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Environmental Health Sciences (NIEHS), and National Institute of Drug Abuse (NIDA) are providing opportunities under the NIH.

Updated: September 04, 2020.

The following table lists funding opportunities listed on various public platforms including the JHU, Frontiers, Brown University and Science Business COVID-19 funding databases.

Updated: 17 August, 2020.

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