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IMPORTANCEMany hospitalized patients with COVID-19 have been treated with convalescent plasma. However, it is uncertain whether this therapy lowers mortality and if so, if the mortality benefit is larger among specific subgroups, such as recipients of plasma with high antibody content and patients treated early in the disease course.OBJECTIVETo examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19.DATA SOURCESOn October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature.STUDY SELECTIONRandomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3,841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of five reviewers.DATA EXTRACTION AND SYNTHESISThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using inverse-variance random-effects model.MAIN OUTCOMES AND MEASURESPrespecified end point was all-cause mortality during hospitalization.RESULTSThirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses demonstrated that transfusion of COVID-19 convalescent plasma was associated with a significant decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio (OR), 0.87 [95% CI, 0.76-1.00]) and matched cohort studies (OR, 0.77 [95% CI, 0.64-0.94]). Meta-analysis of subgroups revealed two important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared to convalescent plasma containing low antibody levels (OR, 0.85 [95% CI, 0.73 to 0.99]). Second, earlier treatment with COVID-19 convalescent plasma was associated with a significant decrease in mortality compared with the later treatment cohort (OR, 0.63 [95% CI, 0.48 to 0.82]).CONCLUSIONS AND RELEVANCECOVID-19 convalescent plasma use was associated with a 13% reduced risk in mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.Key PointsQuestionWhat is the evidence regarding the potential mortality benefit associated with transfusion of convalescent plasma in hospitalized patients with COVID-19?FindingsIn this meta-analysis of 39 randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants, transfusion of convalescent plasma was associated with a 13% mortality benefit. Subgroup analyses revealed that patients treated with plasma containing higher levels of antibodies and patients treated earlier in the course of the disease had a greater mortality benefit associated with COVID-19 convalescent plasma transfusion.MeaningThese findings suggest that transfusion of COVID-19 convalescent plasma is associated with a mortality benefit for hospitalized patients, particularly those treated earlier in the disease course.

INTRODUCTION: Exposure to low oxygen environments (hypoxia) can impair cognitive function; however, the time-course of the transient changes in cognitive function is unknown. In this study, we assessed cognitive function with a cognitive test before, during, and after exposure to hypoxia.METHODS: Nine participants (28 4 yr, 7 women) completed Conners Continuous Performance Test (CCPT-II) during three sequential conditions: 1) baseline breathing room air (fraction of inspired oxygen, FIo2 0.21); 2) acute hypoxia (FIo2 0.118); and 3) recovery after exposure to hypoxia. End-tidal gas concentrations (waveform capnography), heart rate (electrocardiography), frontal lobe tissue oxygenation (near infrared spectroscopy), and mean arterial pressure (finger photoplethysmography) were continuously assessed.RESULTS: Relative to baseline, during the hypoxia trial end-tidal (-30%) and cerebral (-9%) oxygen saturations were reduced. Additionally, the number of commission errors during the CCPT-II was greater during hypoxia trials than baseline trials (2.6 0.4 vs. 1.9 0.4 errors per block of CCPT-II). However, the reaction time and omission errors did not differ during the hypoxia CCPT-II trials compared to baseline CCPT-II trials. During the recovery CCPT-II trials, physiological indices of tissue hypoxia all returned to baseline values and number of commission errors during the recovery CCPT-II trials was not different from baseline CCPT-II trials.DISCUSSION: Oxygen concentrations were reduced (systemically and within the frontal lobe) and commission errors were increased during hypoxia compared to baseline. These data suggest that frontal lobe hypoxia may contribute to transient impairments in cognitive function during short exposures to hypoxia.Uchida K, Baker SE, Wiggins CC, Senefeld JW, Shepherd JRA, Trenerry MR, Buchholtz ZA, Clifton HR, Holmes DR, Joyner MJ, Curry TB. A novel method to measure transient impairments in cognitive function during acute bouts of hypoxia. Aerosp Med Hum Perform. 2020; 91(11):839844.

Background The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. Methods and findings Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician–principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had—or were at risk of progression to—severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (, In an observational study of registry data, Jonathon Senefeld and colleagues study factors related to patient enrollment in the Expanded Access Program for use of COVID-19 convalescent plasma in the United States., Author summary Why was this study done? There was a public health need to provide expedited and broad access to convalescent plasma for the treatment of coronavirus disease 2019 (COVID-19) during the early stages of this public health emergency in the United States. Convalescent plasma was initially administered through regulatory pathways that required per-patient approval, resulting in substantial administrative time. The Expanded Access Program (EAP) was initiated to provide broad access to COVID-19 convalescent plasma and to provide a framework for standardized collection of data describing the safety profile of convalescent plasma. What did the researchers do and find? The EAP provided rapid and broad access to convalescent plasma throughout the US and some US territories and was effective at providing therapy for demographic groups that were severely affected by COVID-19. In addition, the data provide evidence supporting that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19. What do these findings mean? The study design of the EAP may serve as an example for future efforts in response to a rapidly developing infectious disease when broad access to a treatment is needed in areas and demographic groups that are often poorly represented in clinical trials.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge., Regional differences in SARS-CoV-2 variants may affect treatment outcome. Here, the authors show that near-sourced convalescent plasma has higher efficacy, as defined by death within 30 days of transfusion, than plasma sourced more than 150 miles away.