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Severe Covid-19 - therapies
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https://www.nejm.org/doi/full/10.1056/NEJMcp2009575
David A. Berlin, M.D., Roy M. Gulick, M.D., M.P.H.,
and Fernando J. Martinez, M.D.
From Weill Cornell Medicine, New York
In a large cohort of patients with Covid-19, 81% had mild disease, 14% had severe disease, and 5% became critically ill with organ failure; the mortality in the critically ill group was 49%.12 The majority of critically ill patients with Covid-19 receive prolonged mechanical ventilation. People with chronic health conditions such as cardiovascular disease, diabetes mellitus, and obesity are more likely to become critically ill from Covid-19. The incidence of critical illness is also higher among men than among women and higher among persons older than 65 years of age than among younger persons.13-15 However, healthy persons of any age can become critically ill with Covid-19....Patients hospitalized with severe Covid-19 are often treated empirically with antibiotics.3,9 However, bacterial coinfection is rare when patients first present to the hospital.8,39,40 Antibiotics can be discontinued after a short course if signs of bacterial coinfection, such as leukocytosis and focal pulmonary infiltrates, are absent. Although Covid-19 itself can cause prolonged fever, clinicians should be vigilant for nosocomial infections....Patients with Covid-19 who are receiving mechanical ventilation should receive appropriate nutrition and care to prevent constipation and injury to the skin and corneas.
Little is known about the pathogenesis and treatment of this new disease. Preliminary data from a randomized, placebo-controlled trial involving more than 1000 patients with severe Covid-19 suggest that the investigational antiviral agent remdesivir reduces time to recovery,43 and the Food and Drug Administration (FDA) has granted it emergency-use authorization. No agent is currently FDA-approved for the treatment of severe Covid-19. Numerous randomized trials of many other candidate therapies are ongoing (Table 1).
The delayed onset of critical illness in patients with Covid-19 suggests a maladaptive host response to infection.10 Therefore, there is intense interest in the effects of immunomodulating therapies. Glucocorticoids have been used widely for cytokine storm and respiratory failure in patients with Covid-19; however, there is concern that they may prolong viral shedding and lead to secondary infections.58-60 Current guidelines offer conflicting advice on the use of glucocorticoids. The Surviving Sepsis Campaign suggests a short course of glucocorticoids for moderate-to-severe ARDS related to Covid-19,18 whereas the Infectious Diseases Society of America recommends their use only in the context of a clinical trial.62 For reversal of vasopressor-dependent shock in patients with Covid-19, the Surviving Sepsis Campaign recommends low-dose glucocorticoids (hydrocortisone at a dose of 200 mg daily by means of infusion or with intermittent dosing).18
Other immunomodulating agents currently being evaluated for severe Covid-19 include passive immunotherapy with convalescent plasma,56,57 intravenous immunoglobulin, and interleukin-1 and interleukin-6 pathway inhibition.63 Pending results of randomized trials, the risks and benefits of these approaches are also unknown. Candidate therapies for Covid-19 warrant evaluation separately in patients with established severe disease and in those with milder illness to determine whether they reduce the risk of progression.10
May 15, 2020
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