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Unproven Therapy Algorithms for Early SARS-CoV-2 Infection Are Dangerous

  • Rodrigo Diaz Olmos
    Correspondence
    Requests for reprints should be addressed to Rodrigo Diaz Olmos, MD, MSc, PhD, Divisão de Clínica Médica, Hospital Universitário, Universidade de São Paulo, Av. Lineu Prestes, 2565, Cidade Universitaria – Butantã, São Paulo, SP, CEP 05508-000, Brazil.
    Affiliations
    Department of Internal Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil

    University Hospital, Universidade de São Paulo, São Paulo, SP, Brazil
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  • Felício Lopes Roque
    Affiliations
    University Hospital, Universidade de São Paulo, São Paulo, SP, Brazil
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      To the Editor:
      We read with interest the article by McCullough et al
      • McCullough PA
      • Kelly RJ
      • Ruocco G
      • et al.
      Pathophysiological basis and rationale for early outpatient treatment of SARS-CoV-2 (COVID-19) infection.
      about the pathophysiological basis and rationale for early outpatient treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which results in coronavirus disease 2019 (COVID-19). Although the article discusses some significant issues, it has many important drawbacks.
      As the authors pointed out, there are “2 major areas of response to the pandemic: containment of the spread of infection and reducing inpatient mortality.” The first relates to social distancing, mask use, hand hygiene, testing, and isolating infected people and their contacts. The second relates to treating patients who are hospitalized with support measures and drugs that have demonstrated some benefits, such as corticosteroids, and to managing critically ill patients with emphasis on mechanical ventilation. Outside these interventions, all drugs mentioned in the review should not be indicated as early outpatient treatment. Articles postulating such things have the potential to worsen outcomes because they give the false impression that there is an early treatment capable of saving the lives of people infected with COVID-19, and people may relax preventative measures. Brazil is an example of this horrible situation.
      We understand that in a pandemic efforts should be directed to repurposing and developing drugs that might improve hard endpoints when introduced early. But in contrast to what the authors say, good evidence can be produced during a pandemic, and many studies have already shown that hydroxychloroquine,
      • Skipper CP
      • Pastick KA
      • Engen NW
      • et al.
      Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial.
      azithromycin,
      • Cavalcanti AB
      • Zampieri FG
      • Rosa RG
      • et al.
      Hydroxychloroquine with or without azithromycin in mild-to-moderate COVID-19.
      and favipiravir
      • Doi Y
      • Hibino M
      • Hase R
      • et al.
      A prospective randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19.
      have no beneficial effects on clinical outcomes in patients with COVID-19. The beneficial effects of corticosteroids were observed in patients receiving supplemental oxygen,

      RECOVERY Collaborative Group, Horby P, Lim WS, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report [e-pub ahead of print]. N Engl J Med. Accessed January 15, 2021. doi: NEJMoa2021436.

      and not in those with respiratory symptoms alone or after the fifth day of illness as postulated in the treatment algorithm. There is also no indication to initiate anticoagulation based on suspected microthrombosis. Finally, a recent article on potential early treatments did not even mention hydroxychloroquine, azithromycin, or zinc.
      • Kim OS
      • Read SW
      • Fauci AS
      Therapy for early COVID-19. A critical need.
      Algorithms have been used for decades as a clinical and teaching tool to improve patient care, but we fear that the impact of this article might have the opposite effect of its fundamental objective.

      References

        • McCullough PA
        • Kelly RJ
        • Ruocco G
        • et al.
        Pathophysiological basis and rationale for early outpatient treatment of SARS-CoV-2 (COVID-19) infection.
        Am J Med. 2021; 134: 16-22https://doi.org/10.1016/j.amjmed.2020.07.003
        • Skipper CP
        • Pastick KA
        • Engen NW
        • et al.
        Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial.
        Ann Intern Med. 2020; 173: 623-631https://doi.org/10.7326/M20-4207
        • Cavalcanti AB
        • Zampieri FG
        • Rosa RG
        • et al.
        Hydroxychloroquine with or without azithromycin in mild-to-moderate COVID-19.
        N Engl J Med. 2020; 383: 2041-2052https://doi.org/10.1056/NEJMoa2019014
        • Doi Y
        • Hibino M
        • Hase R
        • et al.
        A prospective randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19.
        Antimicrob Agents Chemother. 2020; 64 (e01897-20)https://doi.org/10.1128/AAC.01897-20
      1. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report [e-pub ahead of print]. N Engl J Med. Accessed January 15, 2021. doi: NEJMoa2021436.

        • Kim OS
        • Read SW
        • Fauci AS
        Therapy for early COVID-19. A critical need.
        JAMA. 2020; 324: 2149-2150https://doi.org/10.1001/jama.2020.22813

      Linked Article

      • The Reply
        The American Journal of MedicineVol. 134Issue 5
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          We are aligned with Drs Olmos and Roque that there should be comprehensive medical crisis management as shown in the 4 pillars of pandemic response in the Figure.1 Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begins as a mild upper respiratory tract infection with a prehospital therapeutic window of opportunity, and there is an important “second pillar” of pandemic response that has the objective of reducing to the “hard outcomes” of COVID-19, hospitalization and death.
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