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Viewpoint
May 22, 2020

Translating Science on COVID-19 to Improve Clinical Care and Support the Public Health Response

Author Affiliations
  • 1Division of Infectious Diseases, Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia
  • 2Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor
  • 3Associate Editor, JAMA
JAMA. 2020;323(24):2464-2465. doi:10.1001/jama.2020.9252

Now in its fifth month, the coronavirus disease 2019 (COVID-19) pandemic continues to advance with nearly 5 million documented infections worldwide and with the US having the largest number of infections and deaths globally. The speed of the scientific response to the epidemic has been unprecedented. On January 7, Chinese investigators identified a novel coronavirus as the cause of an unusual cluster of pneumonia cases, and 5 days later the virus genetic sequence was published. By February 21, the first treatment trial had been initiated and March 18 marked the start of the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine trial in humans. The time from the initial viral sequencing to the first in human injection of a candidate vaccine was a record 65 days.

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    2 Comments for this article
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    COVID-19
    Giuliano Ramadori, Professor of Medicine | University Clinic, Internal Medicine, Göttingen, Germany
    Del Rio C and Malani P have spent many efforts to summarize the flood of communication about the most important aspects of the COVID-19-pandemic published in the last five months. By doing that they offer a platform for additional thoughts and discussions. I think it is important to remember how the new coronavirus was „born“. 

    A doctor, Ai Fen, the chief of the emergency unity at the Wuhan Central Hospital, had to deal with several patients with pneumonia of unclear origin and had the idea and the opportunity to ask the laboratory of the hospital to test swabs
    from a patient for SARS-Coronavirus (1). The laboratory had a real-time PCR-kit which could also identify the RNA of several viruses responsible for „atypical pneumonia“ including several betacoronaviruses and SARS-CoV-1 (2).

    Human Coronaviruses belonged to a family of now seven components which have a large sequence similarity. With the exclusion of SARS-CoV-1 and MERS the other four HuCoV are responsible for 10-30% of atypical pneumonias every winter. These viruses use the same receptor the new CoV uses to colonize the human upper and lower airways. Antibodies against those viruses are quite common in the sera of many persons (3), and we do not exactly know how COVID-19-specific the antibodies are which we are measuring in the sera of COVID-19 infected patients (4).

    Serum level of neutralizing antibodies will also decrease with time and their presence does not mean that they will help to clear the virus and to prevent reinfection.

    Under these conditions and considering the not-so-positive past experience with the influenza vaccine, the production of a COVID-19-vaccine represents a true challenge.

    As we have recently learned that pulmonary disease without thrombosis of the pulmonary vessels is mainly responsible for the death of elderly COVID-19-patients with several comorbidities, while other organs supposed to be invaded by the virus seem not to be much damaged, efforts should focus on early supportive care and therapy to avoid development of severe respiratory insufficiency.

    References

    1. Kuo L: Coronavirus:Whuan doctor speaks out against authorities.The Guardian 2020,March 11.
    2. Zhu N,Zhang D, Wang W et al.A novel Coronavirus from patients with pneumonia in China,2019 New Engl J Med2020;382:727-733.
    3. Gorse GJ,Patel GB, Vitale JN,O`Connor Z.:Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum.Clin Vaccine Immunol 2010,17(2):1875-1880.
    4. Du Z, Zhu F, Guo F et al.Detection of antibodies against SARS-CoV-2 in patients with COVID-19.J Med Virol 2020:1-4
    CONFLICT OF INTEREST: None Reported
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    CoVID19: coagulopathy treatment option?
    Camilo Colaco, PhD | ImmunoBiology Ltd
    This Viewpoint summarized the current status of potential drug therapies, vaccine development and convalescent antibodies as treatment. However, it does not discuss progress in clinical care resulting from the increased scientific understanding of the pathophysiology of SARS-CoV2 infection that has the potential to make the largest improvement in clinical care of CoVID19 patients.

    As with earlier coronavirus outbreaks, the current CoVID19 infection has been associated with adult respiratory distress syndrome (ARDS), with worse outcomes in older patients and a systemic inflammation response triggered by a cytokine storm (CS) (1-3). Treatment has thus focussed primarily on oxygen supplementation with
    mechanical ventilation in more acutely ill patients with therapeutic consideration of anti-virals and immunosuppression (1,2).

    However of the three diagnostic criteria that determine hospital admissions of CoVID patients, only acute breathing difficulty and a characteristic lung CT image are consistent with a diagnosis of ARDS. The third, the elevation of blood D-dimer levels, is indicative of some type of coagulation pathophysiology such as disseminated intravascular coaguloapathy (DIC) (3). This suggestion is consistent with a re-evaluation of characteristic CT lung images and autopsy results from patients with CoVID19 which report widespread microthrombi in lung and other tissues and offers an alternate mechanism of disease progression in CoVID19 patients, namely DICS (3).
     
    Most importantly, considering DIC instead of ARDS as the primary pathophysiological problem in CoVID19 suggests a pragmatic therapeutic option with the early treatment of patients with mild breathing difficulties using anticoagulants such as LMW heparin (4). This therapeutic approach is strongly supported by a retrospective analysis of the treatment of CoVID19 patients in China which reported better outcomes in patients treated with LMW heparin, as well as a reduction of IL6 and the CS that is thought to induce the ARDs that is the focus of most current clinical therapies (4).

    It is thus quite likely that the EARLY treatment of CoVID19 patients with anticoagulants such as LMW heparin could result in better patient outcomes and reduce the mortality risk and concomitant fear elicited by the current global CoVID19 pandemic.

    Camilo Colaco
    Camilo.colaco@immunobiology.co.uk

    References

    1. Clinical management of severe acute respiratory infection when COVID-19 is suspected. WHO/2019-nCoV/clinical/2020.4 https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected

    2. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395 (10223):507-13. PubMed PMID: 32007143.

    3. Oudkerk M et.al. Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology Published Online Apr 23 2020. https://doi.org/10.1148/radiol.2020201629
    CONFLICT OF INTEREST: None Reported
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