Impact of air pollution on COVID-19 severity: a systematic review of underlying biological mechanisms

Background Our recent systematic review highlighted key associations between ambient air pollution (AAP) exposure and COVID-19 severity. This systematic review aims to summarise toxicological studies on the biological mechanisms underlying these associations. Methods On 17 July 2025, PubMed, Embase, Scopus and Web of Science were searched for in vitro, in vivo and in silico studies that examined the biological mechanisms of AAP exposure on COVID-19 health outcomes. Two independent reviewers engaged in the selection and data extraction process. The methodological quality of the included studies was assessed with the Toxicological Data Reliability Assessment Tool. The Integrated Network and Dynamical Reasoning Assembler (INDRA) was used to provide visual biomechanistic summaries of the included studies by creating knowledge graphs of the described mechanisms. Results A total of 18 studies were included in this review. Findings consistently indicated that AAP exposure can worsen COVID-19 severity through two key mechanisms 1) increased expression of viral entry factors (e.g. angiotensin-converting enzyme 2 and transmembrane serine protease 2), facilitating infection, and 2) immune dysregulation, resulting in increased inflammation and oxidative stress. These key mechanisms were also identified in the INDRA networks. While studies commonly focused on particulate matter (n=15), similar effects were seen with ultrafine particles and ozone. Conclusion These findings highlight the impact of AAP exposure on COVID-19 health outcomes on the molecular level. The findings of this review illustrate the urgent need for air quality improvements to help shape public health strategies to reduce and prevent future health impacts caused by AAP exposure.