Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

The effect of smoking on COVID-19 severity: A systematic review and meta-analysis.

Various comorbidities represent risk factors for severe coronavirus disease 2019 (COVID-19). The impact of smoking on COVID-19 severity has been previously reported in several meta-analyses limited by small sample sizes and poor methodology. We aimed to rigorously and definitively quantify the effects of smoking on COVID-19 severity. MEDLINE, Embase, CENTRAL, and Web of Science were searched between 1 December 2019 and 2 June 2020. Studies reporting smoking status of hospitalized patients with different severities of disease and/or at least one clinical endpoint of interest (disease progression, intensive care unit admission, need for mechanical ventilation, and mortality) were included. Data were pooled using a random-effects model. This study was registered on PROSPERO: CRD42020180920. We analyzed 47 eligible studies reporting on 32 849 hospitalized COVID-19 patients, with 8417 (25.6%) reporting a smoking history, comprising 1501 current smokers, 5676 former smokers, and 1240 unspecified smokers. Current smokers had an increased risk of severe COVID-19 (risk ratios [RR]: 1.80; 95% confidence interval [CI]: 1.14-2.85; P = .012), and severe or critical COVID-19 (RR: 1.98; CI: 1.16-3.38; P = .012). Patients with a smoking history had a significantly increased risk of severe COVID-19 (RR: 1.31; CI: 1.12-1.54; P = .001), severe or critical COVID-19 (RR: 1.35; CI: 1.19-1.53; P < .0001), in-hospital mortality (RR: 1.26; CI: 1.20-1.32; P < .0001), disease progression (RR: 2.18; CI: 1.06-4.49; P = .035), and need for mechanical ventilation (RR: 1.20; CI: 1.01-1.42; P = .043). Patients with any smoking history are vulnerable to severe COVID-19 and worse in-hospital outcomes. In the absence of current targeted therapies, preventative, and supportive strategies to reduce morbidity and mortality in current and former smokers are crucial.