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Background: Hemoglobin, the primary oxygen-carrying protein in humans, provides the intermediate link between pulmonary oxygen uptake and tissue oxygen consumption. Oxygen transport is greatly influenced by the hemoglobin-oxygen affinity, which is commonly characterized by the metric P50 - defined as the oxygen tension at which 50% of hemoglobin is saturated. Humans with rare hemoglobin mutations causing a low P50 (high hemoglobin-oxygen affinity) have demonstrated remarkable preservation of exercise tolerance at high altitude conditions (~3,000m). However, the influence of a low P50 on V̇O2max at extreme altitudes (>5,500m) remains largely unexamined. To examine the dependence of V̇O2max on P50 and altitude, we developed a computational model of oxygen uptake and utilization. We hypothesized that a low P50 would result in a better maintained V̇O2max at extreme altitudes compared to conditions of normal P50 and high P50 (low hemoglobin-oxygen affinity). Methods: We created a model that couples pulmonary oxygen uptake with systemic oxygen utilization to estimate V̇O2max as a function of P50, hemoglobin concentration, and altitude. Fixed values for cardiac output and tissue oxygen demand for V̇O2max at sea level were assigned in accordance with experimental data. The pulmonary oxygen uptake model assumes a single blood compartment exposed to alveolar gas, from which the arterial oxygen tension may be estimated from venous input. Using the alveolar gas equation, we interpolated respiratory parameters from data obtained during human sojourn to the summit of Everest. The systemic oxygen utilization model uses arterial input parameters along with Michaelis-Menten kinetics to compute oxygen consumption. The Fick principle was used to determine the venous oxygen tension, which was assumed to approximate tissue oxygen tension. From these values, systemic oxygen extraction and V̇O2max were determined as a function of P50, hemoglobin concentration, and altitude. Results: We present the results for several cases of P50 (low, normal, and high) and hemoglobin concentrations as a function of altitude. For a low P50, the model demonstrated a greater arterial oxygen saturation, greater oxygen content, and lower systemic extraction at extreme altitudes compared to values determined for cases of normal and high P50. Additionally, a low P50 led to better maintenance of V̇O2max at ~8,850m (~38% decrease from sea-level V̇O2max) compared to values determined for normal P50 and high P50 (~53% and ~67% decrease from sea-level V̇O2max, respectively, P<0.05). Conclusion: This model demonstrates the importance of P50 in the determination of V̇O2max at various altitudes. At low altitudes, a low P50 does not confer an advantage in terms of oxygen utilization, likely due to diffusive oxygen limitations. However, at high and extreme altitudes, a greater convective oxygen transport associated with a low P50 likely outweighs impairments in oxygen diffusivity. This project was supported by the National Institutes of Health R-35-HL139854. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Recent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Omicron neutralizing activity. Here we reviewed BQ.1.* virus neutralization data from 920 individual patient samples from 43 separate cohorts defined by boosted vaccinations (Vax) with or without recent Omicron COVID-19, as well as infection without vaccination (CCP) to determine level of BQ.1.* neutralizing antibodies and percent of plasma samples with neutralizing activity. More than 90 % of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, and BF.7 with 100 % neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50 % neutralizing titres (GM (GMT 50 ) were 314, 78 and 204 for BQ.1.1, XBB.1 and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naïve subjects who also recently (within 6 months) received at least a third vaccine dose had about half of the GM (GMT 50 ) for all viral variants. Boosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, neutralizing antibody source against the new Omicron BQ.1.1, XBB.1 and BF.7 variants.

Sex hormone concentrations, particularly testosterone, are primary determinants of sex-based differences in athletic and sports performance, and this relationship may inform fair competition and participation for athletes. This article describes the sex-based dichotomy in testosterone and the implications for sex-based differences in individual sports performance, including factors that relate to athletic performance for transgender individuals, and areas of future investigation.

This case study, longitudinal analysis of freestyle swimming performances before and after 2 yr of feminizing gender-affirming hormone therapy of an elite transgender woman (male sex, female gender identity), demonstrates superior performance relative to rank-matched female swimmers and a lower performance gap than previously observed between elite male and female swimmers.

During hypoxic exposure, humans with high-affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared with healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high-affinity hemoglobin [6 females, O2 partial pressure at 50% [Formula: see text] (P50) = 16 ± 1 mmHg] compared with 12 humans with typical affinity hemoglobin (6 F, P50 = 26 ± 1 mmHg). Participants breathed normal room air for a 10-min baseline, followed by 20 min of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 ([Formula: see text]) to ∼50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in 5-min periods throughout the hypoxia exposure, beginning with the last 5 min of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method and the time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high-affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure (normoxia: 7 ± 4 vs. 16 ± 10 ms/mmHg, hypoxia minutes 15–20: 4 ± 3 vs. 14 ± 11 ms/mmHg; group effect: P = 0.02, high-affinity hemoglobin vs. control, respectively). Heart rate variability calculated in both the time (standard deviation of the N-N interval) and frequency (low frequency) domains was lower in humans with high-affinity hemoglobin than in controls (all P < 0.05). Our data suggest that humans with high-affinity hemoglobin may have attenuated cardiac autonomic function.

Abstract Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

ImportancePatients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient.ObjectiveTo assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion.Data SourcesOn August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised.Study SelectionRandomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening.Data Extraction and SynthesisThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled.Main Outcomes and MeauresThe prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma.ResultsThis systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]).Conclusions and RelevanceThese findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.