Incidence and factor analysis for the heat-related illness on the Tokyo 2020 Olympic and Paralympic Games.

Introduction: Among the 43 venues of Tokyo 2020 Olympic Games (OG) and 33 venues of Paralympic Games (PG) were held, the heat island effect was highly expected to cause heat-related illnesses in the outdoor venues with maximum temperatures exceeding 35°C. However, the actual number of heat-related illness cases during the competition was lower than that was initially expected, and it was unclear under what conditions or environment-related heat illnesses occurred among athletes. Object: To clarify the cause and factors contributing to the occurrence of heat-related illness among athletes participating in the Tokyo 2020 Olympic and Paralympic Games. Method: This retrospective descriptive study included 15 820 athletes from 206 countries. From 21 July 2021 to 8 August 2021 for the Olympics, and from 24 August 2021 to 5 September 2021 for the Paralympics. The number of heat-related illness cases at each venue, the incidence rate for each event, gender, home continent, as well as the type of competition, environmental factors (such as venue, time, location and wet-bulb globe temperature (WBGT)), treatment factor and the type of competition were analysed. Results: More number of heat-related illnesses among athletes occurred at the OG (n=110, 76.3%) than at the PG (n=36, 23.7%). A total of 100 cases (100%) at the OG and 31 cases (86.1%) at the PG occurred at the outdoors venues. In the OG, a total of 50 cases (57.9%) occurred during the competition of marathon running and race walking at Sapporo Odori Park. Six of those, were diagnosed with exertional heat illness and treated with cold water immersion (CWI) at OG and one case at PG. Another 20 cases occurred in athletics (track and field) competitions at Tokyo National Olympic Stadium. In total, 10 cases (10.0%) were diagnosed with severe heat illness in the OG and 3 cases (8.3%) in the PG. Ten cases were transferred to outside medical facilities for further treatment, but no case has been hospitalised due to severe condition. In the factor analysis, venue zone, outdoor game, high WBGT (<28°C) and endurance sports have been found to have a higher risk of moderate and severe heat-related illness (p<0.05). The incidence rate and severity could be attenuated by proper heat-related illness treatment (CWI, ice towel, cold IV transfusion and oral hydration) reduced the severity of the illness, providing summer hot environment sports. Conclusion: The Tokyo 2020 Olympic and Paralympic summer games were held. Contrary to expectations, we calculated that about 1 in 100 Olympic athletes suffered heat-related illness. We believe this was due to the risk reduction of heat-related illness, such as adequate prevention and proper treatment. Our experience in avoiding heat-related illness will provide valuable data for future Olympic summer Games.

Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models.

There is an urgent need to develop novel drugs to reduce the mortality from severe infectious diseases with the emergence of new pathogens, including Coronavirus disease 2019 (COVID-19). Although current drugs effectively suppress the proliferation of pathogens, immune cell activation, and inflammatory cytokine functions, they cannot completely reduce mortality from severe infections and sepsis. In this study, we focused on the endothelial cell-specific protein, Roundabout 4 (Robo4), which suppresses vascular permeability by stabilizing endothelial cells, and investigated whether enhanced Robo4 expression could be a novel therapeutic strategy against severe infectious diseases. Endothelial-specific overexpression of Robo4 suppresses vascular permeability and reduces mortality in lipopolysaccharide (LPS)-treated mice. Screening of small molecules that regulate Robo4 expression and subsequent analysis revealed that two competitive small mothers against decapentaplegic (SMAD) signaling pathways, activin receptor-like kinase 5 (ALK5)-SMAD2/3 and ALK1-SMAD1/5, positively and negatively regulate Robo4 expression, respectively. An ALK1 inhibitor was found to increase Robo4 expression in mouse lungs, suppress vascular permeability, prevent extravasation of melanoma cells, and decrease mortality in LPS-treated mice. The inhibitor suppressed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced endothelial barrier disruption and decreased mortality in mice infected with SARS-CoV-2. These results indicate that enhancing Robo4 expression is an efficient strategy to suppress vascular permeability and mortality in severe infectious diseases, including COVID-19, and that small molecules that upregulate Robo4 can be potential therapeutic agents against these diseases.

SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression.

In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2-induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.

Evaluation of the physiological changes in prehospital health-care providers influenced by environmental factors in the summer of 2020 during the COVID-19 pandemic.

AIM: Wearing personal protective equipment (PPE) is essential to prevent infection transmission, but the risk of heatstroke increases with wearing PPE in a humid and hot environment. Therefore, we aimed to examine how environmental parameters change the body physiology in a hot environment during the coronavirus disease (COVID-19) pandemic. METHODS: This was a retrospective cohort study extracted from the MEDIC Japan heatstroke prevention database, which was recorded between 1 August and 7 September, 2020. Its database is a registry collection from seven healthy health-care providers. Subjects recorded their own vital signs (forehead and tympanic temperature, blood pressure, pulse rate, and oxygen saturation) and environmental factors (type of weather, wet-bulb globe temperature [WBGT], air temperature, humidity, and location) every hour during their working shift. RESULTS: From 323 records, a weak positive but statistically significant correlation was observed between WBGT and pulse rate (correlation coefficient [95% confidence interval], r = 0.34 [0.23, 0.45]) and between WBGT and core body temperature. Forehead temperature had a stronger correlation than tympanic temperature (forehead, r = 0.33 [0.21, 0.43]; tympanic, r = 0.17 [0.05, 0.28]), which also showed a larger effect (forehead, η2 = 0.08; tympanic, η2 = 0.05). The effect size of oxygen saturation measured outdoors was large (η2 = 0.30). Forehead temperature increased abruptly at 28°C WBGT and at 33°C air temperature. CONCLUSION: A hot environment significantly affected forehead temperature, and the daytime imposed a high risk of heatstroke. To avoid heatstroke, environmental parameters are important to note as outdoor environments had a large effect on vital sign changes depending on the time of day.