Guidelines:
IDSA Guidelines on Treatment and Management of Covid-19
IDSA site provides additional information on treatments for prophylaxis, outpatients with infection, and hospitalized patients with mild to moderate disease, as well as references for negative treatment trials.
Resource Management:
Maves RC, Downar J, Dichter JR, et al. Triage of scare critical care resources in COVID-19 an implementation guide for regional allocation: An expert panel report of the Task Force for Mass Critical Care and the American College of Chest Physicians. Chest. 2020;158:212-225. A guide to the creation of a triage system including family and healthcare provider support needs.
PMID: 32289312
Imaging:
Ye Z, Zhang Y, Wang Y, Huang Z, Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Eur Radiol. 2020; 30:4381-4389. This review summarizes, and illustrates, a broad range of radiographic manifestations of COVID-19 infection compiled from multiple early case series.
PMID: 32193638
Pharmacologic Treatment - Outpatient:
Antivirals:
Gottlieb RL, Vaca CE, Paredes R et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2022; 386:305-315. This randomized, double-blind, placebo-controlled trial (PINETREE) showed that 3 days of treatment with remdesivir decreased the risk of hospitalization or death by 87% in 562 nonhospitalized patients who had at least one risk factor for Covid-19 progression. Adverse events were higher in the placebo group than in the remdesivir group.
PMID: 34937145
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Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk,nonhospitalized adults with Covid-19. N Engl J Med. 2022; 386:1397-1408. This randomized, controlled trial (EPIC-HR) assessed the impact of nirmatrelvir and ritonavir (paxlovid) dosed every 12 hours for 5 days in 2246 symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe Covid-19. Nirmatrelvir/ritonavir led to an 89.1% relative risk reduction in Covid-19-related hospitalization or death by day 28 compared with placebo, and there was no increase in adverse events.
PMID: 35172054
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Monoclonal Antibodies:
Updated information about monoclonal antibodies and efficacy in the latest COVID-19 variants can be found at: https://www.idsociety.org/covid-19-real-time-learning-network/therapeutics-and-interventions/monoclonal-antibodies/
Ivermectin:
Reis G, Silva EASM, Silva DCM, et al. Effect of early treatment with ivermectin among patients with Covid-19. N Engl J Med. 2022; 386:1721-1731 This segment of a randomized platform study included 1,358 outpatients with confirmed COVID-19 infection and at least 1 risk factor for developing severe infection. Ivermectin for 3 days did not decrease covid-related hospital admissions or emergency department visits.
PMID: 35353979
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Pharmacologic Treatment - Inpatients:
Dexamethasone:
Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19.
RECOVERY Collaborative Group. N Engl J Med. 2021; 384:693-704. This adaptive, randomized controlled study of candidate COVID-19 treatments was the first trial to show a mortality benefit from the use of dexamethasone. A regimen of 6 mg of dexamethasone for up to 10 days reduced 28-day mortality among 6,245 hospitalized COVID-19 patients who were receiving oxygen without mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 – 0.94) or on mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 – 0.81). There was no benefit in patients not requiring oxygen.
PMID: 32678530
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Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID=-19: The CoDEX randomized clinical trial. JAMA. 2020; 324:1307-1316. RCT of dexamethasone vs standard care in 299 patients requiring mechanical ventilation due to COVID-19 ARDS was stopped early upon publication of the RECOVERY trial. Dexamethasone was given as a 20 mg infusion for 5 days followed by a 10 mg infusion for 5 days. After 28 days, the dexamethasone group had a greater number of days alive and free of the ventilator (6.6; 95% CI, 5.0 – 8.2) than the standard care group (4.0; 95% CI, 2.9 – 5.4) with P = .04 for difference between groups. All-cause mortality at 28 days was nearly 60% and did not differ between groups.
PMID: 32876695
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The COVID STEROID 2 Trial Group. Effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: The COVID STEROID 2 Randomized Trial. JAMA. 2021;326: 1807-1817. RCT of 1,000 patients compared 6 mg versus 12 mg of IV dexathemasone in COVID-19 patients requiring at least 10 L/min of supplemental oxygen or mechanical ventilation. There was no statistically significant difference in the primary endpoint of days alive without life support at 28 days (adjusted mean difference 1.3 days, p =.07). The lower 28-day mortality in the 12 mg group did not reach statistical significance (27.1 vs 32.3%, adjusted RR 0.86, 95% CI 0.68 - 1.08).
PMID: 34673895
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Remdesivir:
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 – final report. ACTT-1 study group members. Mehta AK, Zingman BS, Kalil AC, et al. N Engl J Med. 2020; 383:1813-1826. The first iteration of NIAID’s Adaptive COVID-19 Treatment Trial (ACTT) compared remdesivir to placebo in 1,062 hospitalized patients with COVID-19 causing lower respiratory tract infection. Patients receiving remdesivir, given as an infusion for up to 10 days, had a 5 to 7 day reduction in time to recovery, but mortality did not differ. No benefit was observed in the subset of patients requiring mechanical ventilation.
PMID: 32445440
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WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalized patients with COVID-19: final results of the WHO Solidarity randomized trial and updated meta-analyses. Lancet. 2022; 399: 1941-53. Solidarity is an open-label trial that enrolled 14,221 patients from 35 countries and randomly assigned them either to remdesivir (ten daily infusions, unless discharged earlier) or to control. This trial confirmed a lack of impact on mortality in ventilated patients and suggested a small benefit in patients who were on oxygen but not mechanically ventilated. Notably, the confidence intervals in this study were wide, and type of oxygen device was not specified, limiting assessment of effects in patients receiving high-flow versus low-flow oxygen. The Solidarity Trial Consortium also performed a meta-analysis of randomized trials with similar findings.
PMID: 35512728
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IL-6 receptor antagonists:
REMAP-CAP Investigators, Gordon AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med. 2021; 384:1491-1502. Early studies of tocilizumab monotherapy were negative. This multifactorial adaptive platform trial of 803 patients compared tocilizumab and another interlukin-6 antagonist, sarilumab, to standard care, which for the majority of patients included steroids. Both IL-6 antagonists were superior to standard care for the primary measures of organ support-free days and in-hospital mortality. The results of this trial, and similar results in the EMPACTA and RECOVERY trials, suggest a benefit from IL-6 receptor antagonists when used in conjunction with steroids.
PMID: 33631065
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Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(9):795-807. Randomized trial showing faster time to recovery in baricitinib and remdesivir group vs placebo and remdesivir, particularly in patients on high-flow oxygen or non-invasive ventilation.
PMID: 33306283
Anti-complement antibody therapy:
Vlaar APJ, Witzenrath M, van Paassen P, et al. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022; 10:1137-1146. This RCT of 368 patients intubated due to COVID found anti-C5a antibody administered within 48 hours of intubation resulted in a statistically non-significant improvement in 28-day all-cause mortality compared to standard care (32 vs 42%, p = .09). This difference became statistically significant when site-stratification was eliminated from the analysis. The FDA has granted EUA for this drug.
PMID: 36087611
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Anticoagulation:
INSPIRATION Investigators, Sadeghipour P, Talasaz, AH, Rashidi F, et al. Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: The INSPIRATION randomized clinical trial. JAMA. 2021; 27:1620-1630. RCT comparing intermediate vs standard dose prophylactic anticoagulation in COVID-19 ICU patients, showing no significant difference in venous or arterial thrombosis, treatment with ECMO, or 30 day mortality.
PMID: 33734299
REMAP-CAP, ATTACC, ACTIV-4a Investigators. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med. 2021; 385: 777-789. This trial used open-label, adaptive, multiplatform, randomized methodology to compare therapeutic heparin to usual pharmacological DVT prophylaxis and reached futility after enrollment of 1,098 patients. Specifically, there was no difference in survival to hospital discharge or number of days free of cardiovascular or respiratory organ support.
PMID: 34351722
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***For additional information, see the Infectious Diseases Society of America guidelines for COVID-19 treatment.
Ventilatory and Oxygen Support:
Perkins GD, Ji C, Connolly BA, et al. Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial. JAMA. 2022; 327:546-558. This parallel group, adaptive, RCT of 1273 hospitalized adults with O2 sat 94% or less while receiving at least FIO2 0.4 found the CPAP group (no positive inspiratory pressure used) had a better combined endpoint of intubation or 30-day mortality compared to standard O2 therapy (36.3 vs. 44.%) while there was no difference in the combined endpoint between HFNC and standard therapy.
PMID: 35072713
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Arabi YM, Aldekhyl S, Al Qahtani S, et al.. Effect of helmet noninvasive ventilation vs usual respiratory support on mortality among patients with acute hypoxemic respiratory failure due to COVID-19: The HELMET-COVID Randomized Clinical Trial. JAMA. 2022; 328:1063-1072. Unlike the 2021 HENIVOT trial (Free Full Text), this larger study of 320 patients found use of helmet noninvasive ventilation did not reduce the rate of endotracheal intubation compared to usual care which included noninvasive ventilation, HFNC, and standard O2. Of note, HENIVOT did not includej HFNC only for usual care. Neither study found a difference in mortality.
PMID: 36125473
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Frat JP, Quenot JP, Badie J, et al. Effect of high-flow nasal cannula oxygen vs standard oxygen therapy on mortality in patients with respiratory failure due to COVID-19: The SOHO-COVID Randomized Clinical Trial. JAMA. 2022; 328:1212-1222. This RCT of over 700 patients with P/F < 200 mm Hg found no difference in mortality. The standard oxygen group had a higher rate of intubation (45 vs 53%), but noninvasive support was not used in the study.
PMID: 36166027
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Proning:
Alhazzani W, Parhar KKS, Weatherald J et al. Effect of awake prone positioning on endotracheal intubation in patients with COVID-19 and acute respiratory failure: a randomized clinical trial. JAMA. 2022; 327: 2104-2113. This pragmatic, unblinded multicenter trial studied whether awake prone positioning could improve outcomes in 400 non-intubated patients with COVID-19 requiring oxygen (40% or more FiO2) or NIV. When compared to usual care, prone positioning did not significantly reduce endotracheal intubation at 30 days, mortality at 60 days, days free from IMV or NIV, or days free from the ICU or hospital at 60 days. The intervention group proned for a median of 4.8 hours per day. Whether longer duration of daily proning or selection of certain subgroups would show benefit is unknown.
PMID: 35569448
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