Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. In a retrospective study based on a U.S. national registry, we determined the anti–SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti–SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti–SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti–SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.)

BACKGROUND. Convalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. METHODS. Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma. RESULTS. The incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%. CONCLUSION. Given the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19. TRIAL REGISTRATION. ClinicalTrials.gov NCT04338360. FUNDING. Mayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Endurance exercise training studies frequently show modest changes in VO₂max with training and very limited responses in some subjects. By contrast, studies using interval training (IT) or combined IT and continuous training (CT) have reported mean increases in VO₂max of up to ∼1.0 L · min⁻¹. This raises questions about the role of exercise intensity and the trainability of VO₂max. To address this topic we analyzed IT and IT/CT studies published in English from 1965–2012. Inclusion criteria were: 1)≥3 healthy sedentary/recreationally active humans <45 yrs old, 2) training duration 6–13 weeks, 3) ≥3 days/week, 4) ≥10 minutes of high intensity work, 5) ≥1∶1 work/rest ratio, and 6) results reported as mean ± SD or SE, ranges of change, or individual data. Due to heterogeneity (I² value of 70), statistical synthesis of the data used a random effects model. The summary statistic of interest was the change in VO₂max. A total of 334 subjects (120 women) from 37 studies were identified. Participants were grouped into 40 distinct training groups, so the unit of analysis was 40 rather than 37. An increase in VO₂max of 0.51 L ·min⁻¹ (95% CI: 0.43 to 0.60 L · min⁻¹) was observed. A subset of 9 studies, with 72 subjects, that featured longer intervals showed even larger (∼0.8–0.9 L · min⁻¹) changes in VO₂max with evidence of a marked response in all subjects. These results suggest that ideas about trainability and VO₂max should be further evaluated with standardized IT or IT/CT training programs.