EXPLORE!

Special SERIES ONLY EVIDENCES on SARS-CoV-2 (COVID-19) Medical treatment (Part 7)

  2011 Views

Dr KK Aggarwal    07 April 2020

(Source: DHS Science and Technology, Master Question List for COVID-19 (caused by SARS-CoV-2), Weekly Report, 18 March 2020)

 Medical treatment (Part 7) - Are there effective treatments? Vaccines?

What is known?

  • Treatment for COVID-19 largely involves supportive care, including mechanical ventilation and antibiotics to prevent secondary infection as appropriate.1
  • Preliminary reports from two clinical trials in China suggest that favipiravir can potentially improve lung function and diminish recovery time in COVID-19 patients.2
  • According to early results, tocilizumab may be effective for treating severe COVID-19 cases.3
  • Press reports of a small clinical trial suggest that chloroquine can reduce symptom duration.4
  • Combination lopinavir and ritonavir with standard care has been found to be no more effective than standard care alone.5
  • Corticosteroids are commonly given to COVID-19 patients6at risk ofARDS;7 however, the US CDC does not recommend their use.8
  • Several entities are working to produce a SARS-CoV-2 vaccine,9 including NIH/NIAID, 10,11  Moderna Therapeutics and Gilead Sciences, 12-14 and Sanofi with HHS. 15 Moderna has initiated phase 1 clinical vaccine trials in humans in WA state. 16
  • Regeneron Pharmaceuticals has developed potential SARS-CoV-2 antibody therapies.17
  • The development of a coronavirus fusion inhibitor in the lab points to efficacy across multiple human coronaviruses.18
  • Takeda Pharma (Japan) has initiate work to create antibody treatments based on infected patient plasma.19

What do we need to know?

  • Is GS-5734 (remdesivir) effective in vivo (already used in clinical trials under Emergency Use Authorization)?20
  • Is the GLS-5000 MERS vaccine21cross-reactive against SARS-CoV-2?
  • Efficacy of antibody treatments developed for SARS22,23and MERS.24
  • Efficacy of various MERS and SARS Phase I/II vaccines and other therapeutics?
  • Efficacy of viral replicase inhibitors such as beta-D-N4-hydroxycytidine against SARS-CoV-2.25

References

  1.  Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv 2020, 2020.02.06.20020974.
  2. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. New England Journal of Medicine 2020.
  3. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective Treatment of Severe COVID-19 Patients with Tocilizumab. ChinaXiv 2020.
  4. French researcher posts successful Covid-19 drug trial. Connexion: 2020.
  5. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine 2020.
  6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet.
  7. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine.
  8. CDC, Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html.
  9. Amanat F, Krammer F. SARS-CoV-2 vaccines: status report. Journal of Immunology 2020, Early View.
  10. HHS, 2019-nCoV Update. 2020.
  11. Levine J. Scientists race to develop vaccine to deadly China coronavirus. https://nypost.com/2020/01/25/scientists-race-to-develop-vaccine-to-deadly-china-coronavirus/.
  12. A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults 2020.
  13. Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in Healthy Adults 2020.
  14. NIH, NIH clinical trial of remdesivir to treat COVID-19 begins https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins.
  15. Branswell H. Sanofi announces it will work with HHS to develop a coronavirus vaccine. Statnews, Ed. 2020.
  16. Roberts, M., Coronavirus: US volunteers test first vaccine. BBC 2020.
  17. Pharmaceuticals, R., Regeneron has identified hundreds of virus-neutralizing antibodies; plans to initiate large-scale manufacturing mid-April with antibody cocktail therapy. PR Newswire: 2020.
  18. Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S, et al. Inhibition of SARS-CoV-2 infection (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. bioRxiv 2020, 2020.03.09.983247.
  19. Herper M, Feurerstein A. How blood plasma from recovered patients could help treat the new coronavirus. STAT 2020.
  20. Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017, 9 (396).
  21. Yoon IK, Kim JH. First clinical trial of a MERS coronavirus DNA vaccine. The Lancet Infectious Diseases 2019, 19 (9), 924-925.
  22. Coughlin MM, Prabhakar BS. Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential. Reviews in medical virology 2012, 22 (1), 2-17.
  23. ter Meulen J, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F, et al. Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 2006, 3 (7), e237.
  24. CenterWatch, SAB Biotherapeutics wins BARDA MERS treatment contract. https://www.centerwatch.com/articles/14742.
  25. Barnard DL, Hubbard VD, Burton J, Smee DF, Morrey JD, Otto MJ, et al. Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and beta-D-N4-hydroxycytidine. Antivir Chem Chemother 2004, 15 (1), 15-22.

  

Clinical diagnosis (Part 6)

Are there tools to diagnose infected individuals? When, during infection, are they effective?

 What is known?

  • PCR protocols and primers have been shared extensively among international researchers;1-6however, PCR-based diagnostic assays do not differentiate between active and inactive virus.
  • A combination of pharyngeal (throat) RT-PCR and chest tomography seem to be the most effective diagnostic criteria (correctly diagnosing 91.9% of infections).Single throat swabs alone detect 78.2% of true infections.
  • Nasal and pharyngeal swabs seem to be less effective than sputum and bronchoalveolar lavage fluid as diagnostic specimens.8
  • RT-PCR tests can identify asymptomatic cases; SARS-CoV-2 infection was identified in 2/114 individuals that were previously cleared by clinical assessment.9
  • The FDA has released an Emergency Use Authorization that enables laboratories to develop and use tests in-house for patient diagnosis.10 Updated tests from the US CDC are available to states. 11.12
  • US CDC has expanded patient testing criteria to include symptomatic patients at the discretion of the clinician.13
  • Rapid or real-time test kits have been developed by universities and industry, including the Wuhan Institute of Virology,14 BGI, 15 and Cepheid. 16
  • The US CDC is working on serological tests to determine what proportion of the population has been exposed toSARS-CoV-2.17
  • Machine learning tools are under development to predict severe and fatal COVID-19 cases based on CT scans.18

What do we need to know?

  • False positive/negative rates for tests
  • Eclipse phase of infection, i.e., time between infection and detectable disease, in an individual.

References

  1. CDC, 2019 Novel Coronavirus RT-PCR Identification Protocols. https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-detection-instructions.html.
  2. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 2020, 25 (3).
  3. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. New England Journal of Medicine 2020.
  4. Sheridan, C., Coronavirus and the race to distribute reliable diagnostics. https://www.nature.com/articles/d41587-020-00002-2.
  5. WHO, Diagnostic detection of Wuhan coronavirus 2019 by real-time RTPCR -Protocol and preliminary evaluation as of Jan 13, 2020. https://www.who.int/docs/default-source/coronaviruse/wuhan-virus-assay-v1991527e5122341d99287a1b17c111902.pdf?sfvrsn=d381fc88_2(accessed 01/26/2020)
  6. WHO, Novel Coronavirus (2019-nCoV) technical guidance: Laboratory testing for 2019-nCoV in humans. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/laboratory-guidance.
  7. Ren X, Liu Y, Zhen H, Liu W, Guo Z, Chen C, et al. Application and Optimization of RT-PCR in Diagnosis of SARS-CoV-2 Infection. medRxiv 2020.
  8. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020.
  9. Hoehl S, Berger A, Kortenbusch M, Cinatl J, Bojkova D, Rabenau H, et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. New England Journal of Medicine 2020.
  10. FDA, Policy for Diagnostics Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization for Coronavirus Disease-2019 during the Public Health Emergency; Immediately in Effect Guidance for Industry and Food and Drug Administration Staff. 2020.
  11. CDC, 2019 Novel Coronavirus RT-PCR Identification Protocols. https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-detection-instructions.html.
  12. CDC, Situation summary. https://www.cdc.gov/coronavirus/2019-nCoV/summary.html.
  13. BBC, Coronavirus: California declares emergency after death. BBC 2020.
  14. Daily H. Wuhan Institute of Virology, Chinese Academy of Sciences and others have found that 3 drugs have a good inhibitory effect on new coronavirus. Chen, L., Ed. 2020.
  15. BGI, BGI Responds to Novel Coronavirus with Real-Time Detection Kits, Deploys Emergency Team to Wuhan. 2020.
  16. Verdict, Cepheid to develop automated molecular test for coronavirus. Verdict Medical Devices: 2020.
  17. Joseph A. CDC developing serologic tests that could reveal full scope of U.S. coronavirus outbreak. STAT 2020.
  18. Shi W, Peng X, Liu T, Cheng Z, Lu H, Yang S, et al. Deep Learning-Based Quantitative Computed Tomography Model in Predicting the Severity of COVID-19: A Retrospective Study in 196 Patients. SSRN 2020.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

To comment on this article,
create a free account.

Sign Up to instantly get access to 10000+ Articles & 1000+ Cases

Already registered?

Login Now

Most Popular Articles

News and Updates

eMediNexus provides latest updates on medical news, medical case studies from India. In-depth medical case studies and research designed for doctors and healthcare professionals.