Joyner, Michael J.

AbstractIn recent years, there has been an explosion of new approaches (technological, methodological, pharmacological, etc.) designed to improve physical performance for athletes, the military and in other applications. The goal of the present discussion is to review and quantify several ways in which physiology can provide important insights about which tools may lead to improved performance (and may therefore be worth resource investment) and which tools are less likely to provide meaningful enhancement. To address these objectives, we review examples of technological solutions/approaches in terms of the magnitude of their potential (or actual) influences: transformational, moderate, ineffective or undetermined. As one example, if there were a technology which significantly increased arterial oxygen partial pressure by 10%, this would be relatively meaningless in healthy people resting at sea level, where it would have a minimal effect on arterial oxygen content. However, there might be specific situations where such an effect would be very helpful, including at high altitude or in some patient populations. We discuss the importance of quantitative evaluation of putative approaches to performance enhancement and highlight the important role of integrative physiologists in the development and critical appraisal of these approaches. image

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

The totality of evidence favors the efficacy of convalescent plasma to treat COVID-19 when high-titer plasma is administered early in the course of disease or to immunocompromised patients. In this commentary, we frame the findings of L. A.

AbstractIn this short narrative, we highlight some of our experiences leading the US Convalescent Plasma Program at the beginning of the pandemic in the spring and summer of 2020. This includes a brief summary of how the program emerged and high‐level lessons we learned. We also share our impressions about why convalescent plasma was used at scale in the United States, early in the pandemic and share ideas that might inform the use of convalescent plasma in future outbreaks of novel infectious diseases.