There are several types of SARS-CoV-2 and COVID-19 related In vitro diagnostics –
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 currently authorized 166 tests under Emergency Use Authorizations (EUAs); these include 138 molecular tests, 26 antibody tests, and 2 antigen tests. A select few are highlighted below.
|Molecular assay||IVDbio Inc.||Machine-Free, Fast and Accurate Nucleic Acid Diagnoses System for COVID-19||In development|
|Immunoassay||Mologic Ltd||Mologic COVID-19 Rapid Test||In development|
|Immunoassay||Xiamen Wiz Biotech Co. Ltd||Diagnostic Kit (Colloidal Gold) for IgG/IgM Antibody to SARS-COV-2||CE-IVD|
|Immunoassay||Hunan Yonghe-Sun Biotechnology Co., Ltd||SARS-COV-2 specific antibody test kit (Immunochromatography)||RUO|
|Molecular assay||YouSeq Ltd||YouSeq SARS-COV-2 qPCR Test||RUO|
|Molecular assay||LG Chem Life Sciences Company||AdvanSure COVID-19 real-time RT-PCR||CE-IVD|
|Molecular assay||3D Medicines||3DMed 2019-nCoV RT-qPCR Detection Kit||CE-IVD|
|Immunoassay||Beijing Abace Biology Co., Ltd||COVID-19 Antibody (IgG/IgM)Test Kit (Colloidal Gold Immunochromatography)||India CDSCO - CE-IVD|
|Molecular assay||Shimadzu Corp.||2019 Novel Coronavirus Detection Kit||RUO|
|Immunoassay||BIOSYNEX SA||BIOSYNEX COVID-19 BSS||CE-IVD|
The Race for COVID-19 Vaccines
As per the draft landscape of COVID-19 candidate vaccines released by the WHO (July 7, 2020), there are 21 candidate vaccines in clinical evaluation and 139 candidate vaccines in preclinical evaluation [Link]. Researchers are evaluating different strategies, some tested and some novel, to induce the immune system to produce effective antibodies and get a safe and effective vaccine ready by next year.
The vaccine testing process, right from the preclinical trials to the Phase I safety trials, the expanded Phase II (hundreds enrolled) as well as Phase III efficacy trials (thousands enrolled) are required to determine if the vaccine protects against the pathogen. The approval process follows once a vaccine successfully clears these checks. In a pandemic situation like the current crisis, the phases II and III can be combined to save time to reach the ultimate safety and efficacy goals.
Vaccine development is a time-consuming (often many years) and expensive process. Developing a vaccine quickly requires a new paradigm, with many steps executed in parallel. It involves high risk financially as well, including an early manufacturing scale-up plan and set-up expected even before actual results are seen.
With deciphering of the SARS-CoV-2 genome in January, the race to vaccine accelerated at unprecedented pace. As of July 7, 2020, there are 15 vaccines in Phase II and III combined with one vaccine (CanSino Biologics) being approved for military use in China. Overall, the vaccines development can be visualized as below based on their current stage of development.
Currently, there are at least eight approaches explored for the development of a vaccine. These include Virus vaccines (weakened or inactivated form), Viral-vector vaccines (replicating or non-replicating), nucleic acid forms (RNA, DNA), Protein-based vaccines (Subunit or Virus-like Particles) as well as testing whether existing vaccines (e. g. poliovirus or tuberculosis) could elicit a response to the pathogen.
Select vaccines that have reached clinical trials, as well as promising candidates in preclinical trials are highlighted below.
- Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein [Link] (07/10/20)
- Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells [Link] (07/09/20)
- U.S. phase 3 trial of Kevzara (Sarilumab) 400 mg in COVID-19 patients requiring mechanical ventilation fails to meet its primary and key secondary endpoints [Link] (07/02/20)
- TOCIVID-19 prospective phase 2 trial (n=301) results show reduced 30-day lethality for Tocilizumab [Link] (07/02/20)
- Early treatment with Tocilizumab and Methylprednisolone shows better failure-free and overall survival in cases of severe COVID-19 [Link] (06/27/20)
- Tocilizumab, intravenously or subcutaneously administered, reduced risk of invasive mechanical ventilation or death in an Italian study [Link] (06/24/20)
- Siltuximab, via IL-6 signaling inactivation, shows reduced 30-day mortality rate than best supportive care [Link] (06/20/20)
- All patients treated with GM-CSF blocking antibody Mavrilimumab (n=13) show clinical improvement compared with standard care (65%) [Link] (06/16/20)
- Tocilizumab is associated with reduced lethality rate at 30 but not at 14-days, without significant toxicity in a multicenter single-arm phase 2 trial [Link] (06/05/20)
- A retrospective study of 171 patients shows Tocilizumab in the early stages of the inflammatory flare reduces ICU admissions and mechanical ventilation use [Link] (06/05/20)
- An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction (Karolinska Institutet study) [Link] (06/02/20)
- High Favipiravir dose alleviates disease in Syrian hamster model but shows significant toxicity effects [Link] (07/07/20)
- HCQ and lopinavir/ritonavir treatment arms for COVID-19 to be discontinued in Solidarity trial by WHO based on poor interim results [Link] (07/04/20)
- Combinations of nitazoxanide with three other compounds (remdesivir, amodiaquine and umifenovir) exhibit significant synergy based on in silico approaches [Link] (07/01/20)
- A retrospective study of hospitalized patients in Thailand shows 67.7% day-7 clinical improvement rate following Favipiravir treatment with a low loading dose as poor prognostic factor for early clinical response [Link] (07/01/20)
- Berzosertib, an ATR kinase inhibitor in the DDR pathway, seen as a potential repurposed candidate following screening of small molecule library of 430 protein kinase inhibitors [Link] (06/27/20)
- Screening of a repurposing library reveals Cyclosporine as a potent antiviral against SARS-CoV-2 in lung epithelial cells [Link](06/19/20)
- Boceprevir, GC-376, calpain inhibitors II and XII inhibit SARS-CoV-2 replication in cell culture [Link] (06/14/20)
- Retrospective cohort study shows prolonged viral shedding was significantly associated with delayed initiation of Arbidol (7 days after symptom onset) [Link] (06/09/20)
- Remdesivir shows improvements in SARS-CoV-2 infected Rhesus macaque; no respiratory disease, reduced virus viral loads and damage to the lungs [Link] (06/09/20)
- Sofosbuvir, an FDA-approved antiviral drug, shows promise in infected iPSC-derived human brain organoids [Link] (05/31/20)
- Remdesivir Most ‘Beneficial’ In Covid-19 Patients Who Need Extra Oxygen [Link] (05/24/20)
- Triple anti-viral drug shows COVID-19 promise in Hong Kong study [Link] (5/10/20)
- Inhibition of the replication of SARS-CoV-2 in human cells by the FDA approved drug chlorpromazine [Link] (5/7/20)
- FDA issues emergency-use authorization for remdesivir to treat hospitalized patients with severe Covid-19 [Link] (5/2/20)
- Preliminary data show that tocilizumab improved the clinical outcome immediately in severe and critical COVID-19 patients [Link] (4/30/20)
- Gilead says critical study of Covid-19 drug shows patients are responding to treatment [Link] (4/29/20)
- Gilead Virus Drug May Reduce Sperm Count in Mice: Chinese Study [Link] (4/26/20)
- New data on Gilead’s remdesivir, released by accident, show no benefit for coronavirus patients (some experts see the result as inconclusive) [Link] (4/23/20)
- Enisamium inhibits the influenza A virus and SARS-CoV-2 RNA polymerases [Link] (4/22/20)
- New study shows no benefit of hydroxychloroquine to treat COVID-19 [Link] (4/21/20)
- Remdesivir prevents COVID-19 progression in monkeys [Link] (4/19/20)
- Early peek on Remdesivir clinical trial data shows promising results [Link] (4/16/20)
- A couple new compounds (Auranofin, Baicalin, Baicalein and Doxycycline) have been identified to inhibit coronavirus replication in vitro [Link][Link][Link](4/15/20)
- No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement [Link] (4/14/20)
- Hopeful results of Remdesivir for Patients with Severe Covid-19 [Link] (4/11/20)
- Viriom Initiates Phase 2 Clinical Study of Elsulfavirine for Treatment of COVID-19 [Link] (4/8/20)
- Algernon regulatory submission for Ifenprodil human trial in South Korea [Link] (4/7/20)
- A new study shows that among those patients who received lopinavir-ritonavir, the time to clinical improvement was significantly shorter than in patients receiving standard of care alone [Link] (4/6/20)
- EIDD-2801, a new compound inhibits multiple coronaviruses in mice [Link] (4/6/20)
|wdt_ID||Company||Drug/Strategy||Treatment type||Stage of Development||Details|
|1||EMD Serono / Merck KGaA (ANEMONE)||Other||Treatment||Clinical [Phase 2]; Trial ID(s): NCT04448756||M5049|
|2||University of Oxford (RECOVERY)||Other||Treatment||Clinical [Phase 2|3]; Trial ID(s): EudraCT Number: 2020-001113-21;NCT04381936||Dexamethasone|
|3||Sinovac Research and Development Co., Ltd.|Sinovac Biotech Co., Ltd||Inactivated virus||Vaccine||Clinical [Phase 2]: In Phase II, June 2020; Trial ID(s): NCT04352608;NCT04383574||CoronaVac; Inactivated (inactivated + alum); PiCoVacc|
|4||Inovio Pharmaceuticals/Beijing Advaccine Biotechnology/VGXI Inc./ Richter-Helm BioLogics/Ology Bioservices||DNA-based||Vaccine||Clinical [Phase 1]: Phase I initial data expected June 2020; Phase II/III trials start July/August 2020 ; Trial ID(s): NCT04336410||DNA plasmid vaccine with el|
|5||Novavax||Protein subunit||Vaccine||Clinical [Phase 1]; Trial ID(s): NCT04368988||Protein subunit; NVX-CoV2373; Full-length recombinant SARS COV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M|
|6||Eli Lilly / Ab-Cellera (NIH Vaccines Research Center)||Antibodies||Treatment||Clinical [Phase 1 | 2]: Phase 1 started June 2020; results expected end of June 2020; Trial ID(s): NCT04411628;NCT04427501||LY-CoV555 antibody from recovered patients|
|7||Chinese Academy of Medical Sciences|West China Second University Hospital|Yunnan Center for Disease Control and Prevention||Inactivated virus||Vaccine||Clinical [Phase 2]: Phase II began June 2020; Trial ID(s): NCT04412538||Inactivated|
|8||Henan Provincial CDC/ Beijing Institute of Biological Products||Inactivated virus||Vaccine||Clinical [Phase 1 | 2]; Trial ID(s): ChiCTR2000032459||Inactivated|
|9||Regeneron Pharmaceuticals||Antibodies||Treatment||Clinical [Phase 1 | 2]; Trial ID(s): NCT04425629;NCT04426695||Antibody combination REGN-COV2 (REGN10933+REGN10987) against the spike protein|
|10||Wuhan Institute of Biological Products/ Sinopharm||Inactivated virus||Vaccine||Clinical [Phase 2]: Phase III trial approved to start in UAE June 2020; Early Phase I/II trial results released June 2020; Trial ID(s): ChiCTR2000031809||Inactivated|
- Hydroxychloroquine with antibiotics shows poor clinical outcomes compared to conservative treatment in retrospective cohort study from South Korea [Link] (07/07/20)
- A new nickel foam air filter catches, heats and kills the SARS-Cov-2 virus and other pathogens [Link] (07/08/20)
- Corticosteroids lower risk of the primary composite outcome in a single center retrospective study of 205 non-ICU patients hospitalized with COVID-19 pneumonia [Link] (07/04/20)
- Physician-sponsored cohort study suggests histamine blockers (Cetirizine/Famotidine) may act by minimizing the histamine-mediated cytokine storm [Link] (07/06/20)
- Dutch study on Convalescent Plasma as therapy (CONCOVID Study) fails as patients already had high neutralizing antibody titers [Link] (07/03/20)
- Early combination therapy of anti-inflammatory (Corticosteroids and Enoxaparin) and antiviral drugs in moderate to severe COVID-19 cases shows reduced complications and improved clinical outcomes [Link] (06/29/20)
- Convalescent plasma therapy effective in Iran study with high antibody level donors and patients in early stage of critical illness [Link] (06/29/20)
- JAK1/JAK2 inhibitor baricitinib can correct immune abnormalities observed in hospitalized patients and reduce mortality [Link] (06/29/20)
- Multicenter, observational study shows early administration of prolonged methylprednisolone significantly reduces death hazard [Link] (06/20/20)
- Methylprednisolone, a corticosteroid medication, shows better clinical outcome (composite end point) in partially randomized clinical trial [Link] (06/18/20)
- Dexamethasone saves lives in COVID-19: Results from the randomized UK RECOVERY trial [Link] (06/16/20)
- Janus kinase 1/2 inhibitor Ruxolitinib shows positive results in a single arm, non-randomized open phase II trial for patients with defined hyperinflammation [Link] (06/09/20)
- Retrospective cohort study of 280 patients shows lower mortality in the Ivermectin group especially in patients who required higher inspired oxygen or ventilatory support [Link](06/09/20)
- Ten consecutive patients on high-dose oral famotidine show marked improvements of disease related symptoms [Link](06/08/2020)
- Off-label use of commercial cancer drug acalabrutinib (CALQUENCE) leads to rapid improvements in oxygenation [Link] (06/08/20)
- Treatment with Ruxolitinib, a JAK1/2 inhibitor, leads to faster clinical improvement in a phase II RCT for 43 patients [Link] (05/26/20)
- Johns Hopkins School of Public Health finds inverse correlations between COVID-19 and BCG. COVID-19-attributable mortality among BCG-using countries was 5.8 times lower [Link] (04/13/20)
- Johns Hopkins gets FDA approval to test blood plasma therapy to treat COVID-19 patients [Link] (04/04/20)
- Therapeutics startup Celularity announced Thursday morning that it has received FDA clearance to begin a clinical trial of a proposed stem-cell treatment for COVID-19 [Link] (04/02/20)
- Seoul Viosys and SETi’s Violeds Technology Proves 99.9% Sterilization of Coronavirus in 30 Seconds (04/02/20) [Link]
Scientists and clinicians across the globe have responded to the ongoing coronavirus pandemic with a huge, high-quality global research effort to find a treatment for COVID-19. As of June 6, 2020, there are over 3230 trials registered, with up to 1923 Interventional trials and rest comprising mainly of Observational studies (1210), and Diagnosis tests (42).
Additionally, of note is the “Solidarity”, an international clinical trial to help find an effective treatment for COVID-19, launched by the World Health Organization and partners. 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.
Vaccine makers are racing to develop COVID-19 vaccines, and have advanced ten candidates into clinical trials. As of June 6 2020, the global COVID-19 vaccine R&D landscape includes 133 vaccine candidates, of which 10 are in clinical evaluation stages and 123 in preclinical evaluation. The most advanced candidates have recently moved into clinical development, including mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, AZD1222 (ChAdOx1) from University of Oxford & AstraZeneca, INO-4800 from Inovio, LV-SMENP-DC and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute. The researchers at the University of Oxford and AstraZeneca hope to have the first phase 3 data in hand this summer. Numerous other vaccine developers have indicated plans to initiate human testing in 2020.
|Platform||Type of candidate||Developer||Stage||Trial ID|
|Non-Replicating Viral Vector||Adenovirus Type 5 Vector||CanSino Biological Inc./Beijing Institute of Biotechnology||Phase 2||ChiCTR2000031781|
|RNA||LNP-encapsulated mRNA (mRNA-1273)||Moderna/NIAID||Phase 2||NCT04405076|
|Inactivated||Inactivated||Wuhan Institute of Biological Products/ Sinopharm||Phase 1/2||ChiCTR2000031809|
|Inactivated||Inactivated||Beijing Institute of Biological Products/ Sinopharm||Phase 1/2||ChiCTR2000032459|
|Inactivated||Inactivated + alum (PiCoVacc)||Sinovac||Phase 1/2||NCT04352608|
|Non-Replicating Viral Vector||AZD1222 (ChAdOx1)||University of Oxford and AstraZeneca||Phase 2b/3||NCT04324606|
|RNA||3 LNP-mRNAs (BNT162)||BioNTech/Fosun Pharma/Pfizer||Phase 1/2||NCT04368728; 2020-001038-36|
|DNA vaccine||INO-4800||Inovio Pharmaceuticals||Phase 1||NCT04336410|
|Protein subunit||Glycoprotein nanoparticle vaccine + Matrix M (NVX-CoV2373)||Novavax||Phase 1/2||NCT04368988|
|Inactivated||Inactivated||Institute of Medical Biology and Chinese Academy of Medical Sciences||Phase 1||–|
Figure | Profile of COVID-19 vaccine developers by type and geographic location. For partnerships, the location is that of the lead developer. *Excluding China.
A broad classification of currently registered trials based on intervention strategies:
COVID-19 Funding Response
The world is facing an unprecedented challenge with communities and economies everywhere affected by the growing COVID-19 pandemic. 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.
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.
The Coalition for Epidemic Preparedness Innovations (CEPI) is a global alliance financing and coordinating the development of vaccines against emerging infectious diseases. The CEPI is collaborating with GSK and will use their pandemic vaccine adjuvant platform technology to enhance the development of an effective vaccine. 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 is investing in partnering agreements with Novavax, Inc. and The University of Oxford ($4.4 million), Institut Pasteur-led consortium that will include Themis and the University of Pittsburgh (US$4.9 million), and The University of Hong Kong (US$620,000). To date, CEPI has provided initial funding to Curevac, Inc., Inovio Pharmaceuticals, Inc., Moderna, Inc., Novavax, Inc., The University of Hong Kong, The University of Oxford, and The University of Queensland to develop COVID-19 vaccine candidates. CEPI partnered with AstraZeneca to manufacture 300 million globally accessible doses of COVID-19 vaccine. CEPI announced an investment of up to $388 million to accelerate the development and manufacturing of Novavax’ NVX‑CoV2373 vaccine candidate against COVID-19.
Through the Bill and Melinda Gates Foundation, the Microsoft founder and philanthropist plan to help fund factories for seven promising vaccines, even before seeing conclusive data. Two of the programs – at most – will make it through to final development and deployment. The Inovio INO-4800 DNA vaccine is the second vaccine to undertake Phase 1 clinical testing on human subjects thanks to backing from the foundation.
Biomedical Advanced Research and Development Authority (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.
An additional €675 million of EU’s Horizon 2020 funding is to be diverted into research on vaccines, diagnostics and therapeutics against COVID-19, bringing the total investment in pandemic R&D from the programme to €1 billion. European Commission helped raise €7.4B to fund global research on vaccines and treatments for COVID-19.
The Division of Research, Innovation & Ventures (DRIVe) BAA (Budget $750,000) has opportunities for Diagnostic assays, screening and model development, vaccines, advanced manufacturing.
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.
The National Science Foundation (NSF, $256,000), Department of Defense (DOD) are among other prominent agencies.
Deutsche Forschungsgemeinschaft (German Research Foundation), Nordic Trial Alliance, UK Research and Innovation (UKRI) and several other international funding agencies have also come forward with various initiatives.