Senefeld, Jonathon W

Longitudinal studies assessing durability of the anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) humoral immune response have generated conflicting results. This has been proposed to be due to differences in patient populations, the lack of standardized methodologies, and the use of assays that measure distinct aspects of the humoral response.

Background: The US Food and Drug Administration authorized COVID-19 convalescent plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the USA. Methods: We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data. Results: CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = −0.52, p=0.002) between CCP usage per hospital admission and deaths occurring 2 weeks after admission, and this finding was robust to examination of deaths taking place 1, 2, or 3 weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021. Conclusions: A strong inverse correlation between CCP use and mortality per admission in the USA provides population-level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths. Funding: There was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.

AbstractIn the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID‐19), including among patients with innate or acquired immunosuppression. However, the association between COVID‐19‐associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched‐control registry study of 143 COVID‐19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID‐19 patients with immunosuppression. We review clinical features and treatment protocols of COVID‐19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID‐19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune‐deficient and immune‐suppressed patients with COVID‐19 warrants further investigation.

World-class athletes are substantively faster, wearing marathon racing shoes with technological advancements than other shoes when competing in the marathon. Our findings suggest that technological advances in footwear contributed to the recent improvements in marathon finishing times among elite runners and in record-setting marathon performances. This investigation highlights the importance of sports analytics and may have broad implications for the regulation of running footwear during competition.

Abstract Elite performing men continue to record faster record times in running events compared to women. These sex‐based differences in running speed and endurance in humans are expected based on sexual dimorphisms that contribute to differences in the determinants of aerobic performance. Comparatively, the sexual dimorphisms contributing to sex‐based differences in elite aerobic performance are not ubiquitous across other species that compete in running events. The purpose of this review is to offer a framework and model for ongoing discussions of the physiological determinants and ultimately limits of physical performance. The records for average running speed of champion athletes were delineated by sex for thoroughbred horses, greyhound dogs, and humans. Male and female performances within each of these species are being optimized by training, nutrition, and financial incentives, and are approaching a performance maximum. For horses and greyhounds breeding also plays a role. Analysis of athletic records shows that there is a sex‐related difference of ~10% or more in elite athletic performance for humans; however, the upper limit of performance does not appear to be different between sexes for thoroughbred horses and greyhound dogs. In the context of the nil sex differences in running performance in thoroughbreds and greyhounds, we discuss the physiological role of sexual dimorphisms on sex‐specific limits to running performance. We highlight that studies on both human and animal performance in athletic events stimulate critical physiological questions and drive novel research.

ABSTRACT Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO 3 − ) supplementation in young, healthy men and women, it is unclear if participant and environmental factors modulate the well-described ergogenic effects—particularly relevant factors include biological sex, aerobic fitness, and fraction of inspired oxygen (F i O 2 ) during exercise. To address this limitation, the literature was systematically reviewed for randomized, crossover, placebo-controlled studies reporting exercise performance outcome metrics with NO 3 − supplementation in young, healthy adults. Of the 2033 articles identified, 80 were eligible for inclusion in the meta-analysis. Random-effects meta-analysis demonstrated that exercise performance improved with NO 3 − supplementation compared with placebo ( d = 0.174; 95% confidence interval (CI), 0.120–0.229; P < 0.001). Subgroup analyses conducted on biological sex, aerobic fitness, and F i O 2 demonstrated that the ergogenic effect of NO 3 − supplementation was as follows: 1) not observed in studies with only women ( n = 6; d = 0.116; 95% CI, −0.126 to 0.358; P = 0.347), 2) not observed in well-trained endurance athletes (≥65 mL·kg −1 ·min −1 ; n = 26; d = 0.021; 95% CI, −0.103 to 0.144; P = 0.745), and 3) not modulated by F i O 2 (hypoxia vs normoxia). Together, the meta-analyses demonstrated a clear ergogenic effect of NO 3 − supplementation in recreationally active, young, healthy men across different exercise paradigms and NO 3 − supplementation parameters; however, the effect size of NO 3 − supplementation was objectively small ( d = 0.174). NO 3 − supplementation has more limited utility as an ergogenic aid in participants with excellent aerobic fitness that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g., women) are needed to advance the study of NO 3 − supplementation; however, additional descriptive studies of young, healthy men may have limited utility.