Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized 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 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-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 reported that transfusion of COVID-19 convalescent plasma was associated with a 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, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with 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 decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of 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.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

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.

A Novel Method to Measure Transient Impairments in Cognitive Function During Acute Bouts of Hypoxia.

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.