TABLE 2.

Current therapies for severely and critically ill patients with COVID-19

Drug	Mechanism of activity	Dosing	Risks and precautions	Clinical trial highlights	NIH Guideline Recommendation
Remdesivir	Binds to the viral RNA-dependent RNA polymerase, inhibiting viral replication through premature termination of RNA transcription	Obtain drug through FDA Emergency pathway 200 mg IV on day 1, then 100 mg IV daily for 5–10 days Dose adjustments: •Renal impairment: avoid use if eGFR <30 ml/min or dialysis •Hepatic impairment: avoid use if ALT or AST are >5 times ULN	•Nausea, vomiting •Transient elevations in AST or ALT •Mild, reversible PT prolongation The IV formulation is made with cyclodextrin, which is renally eliminated and accumulation may cause nephrotoxicity	Beigel et al39: •Median recovery time was 11 days for remdesivir versus 15 days for placebo (P < .001) •Mortality at 14 days was 7% for remdesivir versus 12% for placebo (p = ns)	•Because supplies are limited, prioritize for use in hospitalized patients with COVID-19 who require supplemental oxygen but who do not require oxygen delivery through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO (B1) •Insufficient data to recommend either for or against use in patients with mild or moderate COVID-19
Dexamethasone	Anti-inflammatory effects of corticosteroids may prevent or mitigate the systemic inflammatory response in patients with severe COVID-19	6 mg IV/PO daily for up to 10 days	•Hyperglycemia, secondary infections, psychiatric effects, avascular necrosis	Recovery trial33 •Mortality in mechanically ventilated patients was 29% on dex versus 41% with usual care alone •Mortality in patients requiring oxygen was 23% on dex versus 26% with usual care alone	•Recommended for the treatment of COVID-1list9 in hospitalized patients who are mechanically ventilated (A1) and in hospitalized patients who require supplemental oxygen but who are not mechanically ventilated (B1) •Recommends against use for the treatment of COVID–19 in patients who do not require supplemental oxygen (A1)
Convalescent plasma, and SARS-CoV-2 immune globulins	Plasma from donors who have recovered from COVID-19 includes antibodies to SARS-CoV-2; both products may help suppress the virus and modify the inflammatory response	Follow the FDA EIND guidance, or use the national expanded access program	•Risk for transfusion reactions (fever, anaphylaxis, lung injury, infectious transmission) •Theoretical risk of antibody-mediated enhancement of infection	Valk et al95 •Very low-certainty evidence on effectiveness and safety	•Insufficient data to recommend either for or against use for the treatment of COVID-19
IL-1 inhibitors (eg, anakinra)	Endogenous IL-1 is elevated in COVID-19 and CAR-T mediated CRS	Varies; the IV formulation is not approved by the FDA	•No significant safety concerns in sepsis trials •Increased infection rates with prolonged use	Limited data	•Insufficient clinical data to recommend either for or against use of these agents for the treatment of COVID-19 (AIII)
IL-6 inhibitors (eg, tocilizumab, sarilumab)	Blocks inflammatory pathway via IL-6 receptor inhibition	Tocilizumab: 8 mg/kg (max 800 mg) IV ×1 or 324 mg SQ ×1; a second dose may be given within 24 h if no improvement Sarilumab: 400 mg IV ×1; the IV formulation is not approved by the FDA	•Infusion-related reactions •GI perforation •Changes in neutrophils, platelets, lipids, and liver enzymes •HBV reactivation	Limited data	•Recommends against use for the treatment of COVID-19, except in a clinical trial (B1)

Note: Rating of recommendations: A = strong; B = moderate; C = optional. Rating of evidence: I = one or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II =one or more well-designed, nonrandomized trials or observational cohort studies; III =expert opinion.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAR-T, chimeric antigen receptor T cell; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; ECMO, extracorporeal membrane oxygenation; eGFR, estimated glomerular filtration rate; EIND, emergency investigational new drug; FDA, Food and Drug Administration; GI, gastrointestinal; HBV, hepatitis B virus; IV, intravenous; PO, oral; PT, prothrombin time; SARS, severe acute respiratory syndrome;SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SQ, subcutaneous; ULN, upper limit of normal.