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In microgravity environments, such as the International Space Station (ISS), this mode of transmission requires heightened vigilance and preventive measures due to the prolonged suspension of virus-laden particles, which increases the risk of infection. Using the COVID Airborne Risk Assessment (CARA) tool, we assess the risk of airborne transmission of respiratory viruses, using SARS-CoV-2 as a case study, in microgravity by simulating the emission, dispersion, and inhalation of virus-laden particles. Our simulations show that the unique conditions of microgravity allow these particles to remain airborne for more extended periods compared to Earth, leading to a 286-fold increase in virus concentration in the air and resulting in nearly twice the probability of infection for a susceptible host. We also evaluated the effectiveness of preventive measures. We found that facemasks could reduce the risk by up to 23%, while continuous HEPA filtration at five air changes per hour proves crucial for managing air quality and minimizing infection risks by reducing airborne virus concentration by 99.79%. To explore potential effects of spaceflight-induced immune suppression on transmission risk, we modeled hypothetical scenarios with increased viral shedding based on herpesvirus reactivation data. An 8-fold increase in viral load (as observed for herpesviruses in space) raised infection probability by 12 percentage points above baseline. Sensitivity analysis with 4-fold and 16-fold increases showed infection risk scales proportionally with viral shedding intensity. Although facemasks and air filtration help mitigate the risk, their effectiveness diminishes when viral load is elevated. Enhancing host immunity through vaccination or other interventions is vital, potentially reducing infection probability by up to 14.17% when combined with HEPA filtration.<\/jats:p>","DOI":"10.1038\/s41526-026-00590-4","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T03:16:10Z","timestamp":1775013370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling the risk of airborne transmission of respiratory viruses in microgravity"],"prefix":"10.1038","volume":"12","author":[{"given":"Chayanin","family":"Sararat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natnicha","family":"Jiravejchakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawin","family":"Nawattanapaiboon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charin","family":"Modchang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"590_CR1","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2021.0076","volume":"12","author":"A Henriques","year":"2022","unstructured":"Henriques, A. et al. 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