Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Tumor Necrosis Factor a (TNFα), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1β, and TNFα is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management.

Practicing physical activity in a hot and humid climate (HHC) is becoming increasingly common due to anthropogenic climate change and the growing number of international sports events held in warm countries. The aim of this study was to understand the physiological and psychological effects of breathing two air temperatures during cycling exercise in HHC. Ten male athletes performed two sessions of exercise in HHC (T°: 32.0 ± 0.5 °C, relative humidity: 78.6 ± 0.7%) during which they breathed hot air (HA, 33.2 ± 0.06 °C) or temperate air (TA, 22.6 ± 0.1 °C). Each session was composed of 30 min of pre-fatigue cycling at constant intensity, followed by a 10 min self-regulated performance. During pre-fatigue, TA induced a better feeling score and a lower rating of perceived effort (respectively, +0.9 ± 0.2, p < 0.05; 1.13 ± 0.21; p < 0.05) with no changes in physiological parameters. During performance, oxygen consumption and mechanical workload were increased by TA (respectively, +0.23 ± 0.1 L min⁻¹, p < 0.05 and +19.2 ± 6.1 W, p < 0.01), whereas no significant differences were observed for psychological parameters. Reducing the breathed air temperature decreased the discomfort induced by HHC during exercise and increased the performance capacity during self-regulated exercise. Thus, breathed air temperature perception is linked to the hardship of training sessions and directly contributes to the performance decrease in HHC.