Senefeld, Jonathon W.

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.

Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO 3 − ) supplementation ( e.g. beetroot juice) 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, cross‐over, placebo‐controlled studies reporting exercise performance outcome metrics with NO 3 − supplementation in young, healthy adults. There were 2,033 articles identified, and 80 articles met inclusion criteria for the meta‐analysis. Random‐effects meta‐analysis demonstrated that exercise performance was improved with NO 3 − supplementation compared to placebo ( d =0.174, 95% 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: 1) not observed in studies with only women ( n =6, d=0.116, 95% CI [−0.126–0.358], P =0.347), 2) not observed in participants with moderate aerobic fitness (less than 45 mL·kg −1 ·min −1 ; n =4, d =0.168, 95% CI [−0.134–0.469], P =0.276) or elite aerobic fitness (65 mL·kg −1 ·min −1 or greater; n =26, d =0.021, 95% CI [−0.103–0.144], P =0.745) and 3) was not modulated by F i O 2 (hypoxia: n =17, d =0.214, 95% CI [0.054–0.375], P =0.009 vs. normoxia n =97, d =0.175, 95% CI [0.114–0.237], P <0.001). Together, the meta‐analyses demonstrated a clear ergogenic effect of NO 3 − supplementation in recreationally‐active, young, healthy men across many different exercise paradigms and NO 3 − supplementation parameters; however, the effect size of NO 3 − supplementation was objectively small . Although NO 3 − supplementation may be effective in moderately fit, healthy men, NO 3 − supplementation has limited utility as an ergogenic aid in participants 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. Figure 1 Figure 2

The timing and magnitude of sex differences in athletic performance during early human development, prior to adulthood, is unknown. Objective To compare swimming velocity of boys and girls for all Olympic‐length freestyle swimming events to determine the age of divergence in swimming performance. Methods We collected the all‐time top 100 U.S. freestyle swimming performance times of boys and girls age 5 to 18 years for the 50m to 1500m events. Results Swimming performance improved with increasing age for boys and girls ( p <0.001) until reaching a plateau, which initiated at a younger age for girls (15 years) than boys (17 years; sex×age; p <0.001). Prior to age 10, the top 5 swimming records for girls were 3% faster than the top boys ( p <0.001). For the 10 th –50 th places, however, there were no sex‐related differences in swimming performance prior to age 10 ( p =0.227). For both the top 5 and 10 th –50 th places, the sex difference in performance increased from age 10 (top 5, 2.5%; 10 th –50 th places, 1.0%) until age 17 (top 5, 7.6%; 10 th –50 th places, 8.0%). For all places, the sex difference in performance at age 18 was larger for sprint events (9.6%; 50–200m) than endurance events (7.1%; 400–1500m; p <0.001). Additionally, the sex‐related difference in performance increased across age and US ranking from 2.4% for 1 st place to 4.3% for 100 th place ( p <0.001), indicating less depth of performance in girls than boys. However, annual participation was ~20% higher in girls than boys for all ages ( p <0.001). Conclusion The top 5 girls demonstrated faster swimming velocities and the 10 th –50 th place girls demonstrated similar swimming velocities than boys (until ~10 years). After age 10, however, boys demonstrated increasingly faster swimming velocities than girls until 17 years. Collectively, these data suggest girls are faster, or at least not slower, than boys prior to the performance‐enhancing effects of puberty. Support or Funding Information This study was supported by the National Institutes of Health R‐35‐HL139854‐02 (MJJ), HL139854‐02S1 (AJC), 5T32DK007352‐40 (JWS), and the Mayo Foundation. Elite swimming performance. Mean swimming velocity from 5 to 18 years of the top 100 fastest US boys (blue circles) and girls (red triangles) for the 50, 100, 200, 400, 800 and 1500m freestyle swimming distances. Figure 1 Sex differences in performance of the top 5 places. The primary plot (heat map) displays the sex differences in swimming velocity (% boy’s swimming velocity) of the top 5 US rankings in each freestyle event distance and age, negative values (red) indicate faster performance of girls. The top displays the mean sex difference across age, and the right plot displays the mean sex difference across swimming event distance. Figure 2