{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:20:53Z","timestamp":1776327653563,"version":"3.50.1"},"reference-count":62,"publisher":"European Respiratory Society (ERS)","issue":"178","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir Rev"],"accepted":{"date-parts":[[2025,8,10]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>On 17 July 2025, PubMed, Embase, Scopus and Web of Science were searched for <jats:italic>in vitro<\/jats:italic>, <jats:italic>in vivo<\/jats:italic> and <jats:italic>in silico<\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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 (<jats:italic>e.g.<\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1183\/16000617.0070-2025","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:30:15Z","timestamp":1759912215000},"page":"250070","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of air pollution on COVID-19 severity: a systematic review of underlying biological mechanisms"],"prefix":"10.1183","volume":"34","author":[{"given":"Laura","family":"Houweling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Rots","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizan D.","family":"Bloemsma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"van Vorstenbosch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Del Motto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel C.H.","family":"Vermeulen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke H.","family":"Maitland-Van der Zee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Korneliusz","family":"Golebski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George S.","family":"Downward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"2025100801300731000_34.178.250070.1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bj.2020.04.007","article-title":"COVID-19: the first documented coronavirus pandemic in history","volume":"43","author":"Liu","year":"2020","journal-title":"Biomed J"},{"key":"2025100801300731000_34.178.250070.2","unstructured":"World Health Organization . WHO COVID-19 dashboard. Date last updated: 2025. Date last accessed: 2 May 2025. https:\/\/data.who.int\/dashboards\/covid19"},{"key":"2025100801300731000_34.178.250070.3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000507423","article-title":"COVID-19 outbreak: an overview","volume":"64","author":"Ciotti","year":"2019","journal-title":"Chemotherapy"},{"key":"2025100801300731000_34.178.250070.4","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13196"},{"key":"2025100801300731000_34.178.250070.5","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.3390\/ijms23031716","article-title":"SARS-CoV-2-specific immune response and the pathogenesis of COVID-19","volume":"23","author":"Gusev","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2025100801300731000_34.178.250070.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"2025100801300731000_34.178.250070.7","doi-asserted-by":"crossref","first-page":"1195871","DOI":"10.3389\/fimmu.2023.1195871","article-title":"SARS-CoV-2 and the host\u2013immune response","volume":"14","author":"Maison","year":"2023","journal-title":"Front Immunol"},{"key":"2025100801300731000_34.178.250070.8","doi-asserted-by":"crossref","first-page":"988604","DOI":"10.3389\/fcimb.2022.988604","article-title":"Immune response induced by novel coronavirus infection","volume":"12","author":"Sun","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2025100801300731000_34.178.250070.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01091-0"},{"key":"2025100801300731000_34.178.250070.10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1146\/annurev-publhealth-052120-101420","article-title":"Environmental factors influencing COVID-19 incidence and severity","volume":"43","author":"Weaver","year":"2022","journal-title":"Annu Rev Public Health"},{"key":"2025100801300731000_34.178.250070.11","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3390\/biom14030296","article-title":"Association of altered plasma lipidome with disease severity in COVID-19 patients","volume":"14","author":"Zhang","year":"2024","journal-title":"Biomolecules"},{"key":"2025100801300731000_34.178.250070.12","doi-asserted-by":"crossref","first-page":"619","DOI":"10.3390\/metabo12070619","article-title":"Plasma oxylipins and their precursors are strongly associated with COVID-19 severity and with immune response markers","volume":"12","author":"Karu","year":"2022","journal-title":"Metabolites"},{"key":"2025100801300731000_34.178.250070.13","doi-asserted-by":"publisher","DOI":"10.1370\/afm.3145"},{"key":"2025100801300731000_34.178.250070.14","unstructured":"World Health Organization . Post COVID-19 condition (long COVID). Date last updated: 7 December 2022. Date last accessed: 2 May 2025. www.who.int\/europe\/news-room\/fact-sheets\/item\/post-covid-19-condition"},{"key":"2025100801300731000_34.178.250070.15","unstructured":"World Health Organization . Ambient (outdoor) air pollution. Date last updated: 24 October 2024. Date last accessed: 2 May 2025. www.who.int\/news-room\/fact-sheets\/detail\/ambient-(outdoor)-air-quality-and-health"},{"key":"2025100801300731000_34.178.250070.16","doi-asserted-by":"crossref","first-page":"117351","DOI":"10.1016\/j.envres.2023.117351","article-title":"The effect of the urban exposome on COVID-19 health outcomes: a systematic review and meta-analysis","volume":"240","author":"Houweling","year":"2023","journal-title":"Environ Res"},{"key":"2025100801300731000_34.178.250070.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp7832"},{"key":"2025100801300731000_34.178.250070.18","doi-asserted-by":"crossref","first-page":"100608","DOI":"10.1016\/j.lanepe.2023.100608","article-title":"Ambient air pollution exposure linked to long COVID among young adults: a nested survey in a population-based cohort in Sweden","volume":"28","author":"Yu","year":"2023","journal-title":"Lancet Reg Health Eur"},{"key":"2025100801300731000_34.178.250070.19","doi-asserted-by":"crossref","first-page":"05029","DOI":"10.7189\/jogh.12.05029","article-title":"Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome","volume":"12","author":"Ferreira","year":"2022","journal-title":"J Glob Health"},{"key":"2025100801300731000_34.178.250070.20","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3390\/idr15050060","article-title":"Impact of ambient air pollution exposure on long COVID-19 symptoms: a cohort study within the Saudi Arabian population","volume":"15","author":"Saleh","year":"2023","journal-title":"Infect Dis Rep"},{"key":"2025100801300731000_34.178.250070.21","doi-asserted-by":"crossref","first-page":"7511","DOI":"10.3390\/ijerph19127511","article-title":"Recent insights into particulate matter (PM2.5)-mediated toxicity in humans: an overview","volume":"19","author":"Thangavel","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"2025100801300731000_34.178.250070.22","first-page":"182","article-title":"How do inflammatory mediators, immune response and air pollution contribute to COVID-19 disease severity? A lesson to learn","volume":"11","author":"Signorini","year":"2021","journal-title":"Life (Basel)"},{"key":"2025100801300731000_34.178.250070.23","doi-asserted-by":"crossref","first-page":"146464","DOI":"10.1016\/j.scitotenv.2021.146464","article-title":"Association of COVID-19 transmission with high levels of ambient pollutants: Initiation and impact of the inflammatory response on cardiopulmonary disease","volume":"779","author":"Lai","year":"2021","journal-title":"Sci Total Environ"},{"key":"2025100801300731000_34.178.250070.24","doi-asserted-by":"crossref","first-page":"153964","DOI":"10.1016\/j.scitotenv.2022.153964","article-title":"Role of angiotensin-converting enzyme 2 in fine particulate matter-induced acute lung injury","volume":"825","author":"Zhu","year":"2022","journal-title":"Sci Total Environ"},{"key":"2025100801300731000_34.178.250070.25","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.23489"},{"key":"2025100801300731000_34.178.250070.26","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202211325"},{"key":"2025100801300731000_34.178.250070.27","doi-asserted-by":"crossref","first-page":"37002","DOI":"10.1289\/EHP9112","article-title":"Automated network assembly of mechanistic literature for informed evidence identification to support cancer risk assessment","volume":"130","author":"Scholten","year":"2022","journal-title":"Environ Health Perspect"},{"key":"2025100801300731000_34.178.250070.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2009.05.013"},{"key":"2025100801300731000_34.178.250070.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2018.04.014"},{"key":"2025100801300731000_34.178.250070.30","doi-asserted-by":"crossref","first-page":"8410","DOI":"10.3390\/ijerph17228410","article-title":"Diesel particulate matter 2.5 induces epithelial-to-mesenchymal transition and upregulation of SARS-CoV-2 receptor during human pluripotent stem cell-derived alveolar organoid development","volume":"17","author":"Kim","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"2025100801300731000_34.178.250070.31","doi-asserted-by":"crossref","first-page":"100141","DOI":"10.1016\/j.jacig.2023.100141","article-title":"Curbside particulate matter and susceptibility to SARS-CoV-2 infection","volume":"2","author":"Miyashita","year":"2023","journal-title":"J Allergy Clin Immunol Glob"},{"key":"2025100801300731000_34.178.250070.32","doi-asserted-by":"crossref","first-page":"108131","DOI":"10.1016\/j.envint.2023.108131","article-title":"On fine particulate matter and COVID-19 spread and severity: an in vitro toxicological plausible mechanism","volume":"179","author":"Marchetti","year":"2023","journal-title":"Environ Int"},{"key":"2025100801300731000_34.178.250070.33","doi-asserted-by":"crossref","first-page":"579964","DOI":"10.3389\/fgene.2020.579964","article-title":"The secretive liaison of particulate matter and SARS-CoV-2. A hypothesis and theory investigation","volume":"11","author":"Mescoli","year":"2020","journal-title":"Front Genet"},{"key":"2025100801300731000_34.178.250070.34","doi-asserted-by":"crossref","first-page":"1161135","DOI":"10.3389\/fimmu.2023.1161135","article-title":"PM10 promotes an inflammatory cytokine response that may impact SARS-CoV-2 replication in vitro","volume":"14","author":"Mar\u00edn-Palma","year":"2023","journal-title":"Front Immunol"},{"key":"2025100801300731000_34.178.250070.35","doi-asserted-by":"crossref","first-page":"118451","DOI":"10.1016\/j.envres.2024.118451","article-title":"Exposure to urban particulate matter alters responses of olfactory mucosal cells to SARS-CoV-2 infection","volume":"249","author":"Shahbaz","year":"2024","journal-title":"Environ Res"},{"key":"2025100801300731000_34.178.250070.36","doi-asserted-by":"crossref","first-page":"175979","DOI":"10.1016\/j.scitotenv.2024.175979","article-title":"Shedding light on the cellular mechanisms involved in the combined adverse effects of fine particulate matter and SARS-CoV-2 on human lung cells","volume":"952","author":"Marchetti","year":"2024","journal-title":"Sci Total Environ"},{"key":"2025100801300731000_34.178.250070.37","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1021\/acs.est.1c07172","article-title":"Exogenous chemical exposure increased transcription levels of the host virus receptor involving coronavirus infection","volume":"56","author":"Jin","year":"2022","journal-title":"Environ Sci Technol"},{"key":"2025100801300731000_34.178.250070.38","doi-asserted-by":"crossref","first-page":"136887","DOI":"10.1016\/j.jhazmat.2024.136887","article-title":"The influence of PM2.5 exposure on SARS-CoV-2 infection via modulating the expression of angiotensin converting enzyme II","volume":"485","author":"Lin","year":"2025","journal-title":"J Hazard Mater"},{"key":"2025100801300731000_34.178.250070.39","doi-asserted-by":"crossref","first-page":"110722","DOI":"10.1016\/j.envres.2021.110722","article-title":"Exposure to particulate matter upregulates ACE2 and TMPRSS2 expression in the murine lung","volume":"195","author":"Sagawa","year":"2021","journal-title":"Environ Res"},{"key":"2025100801300731000_34.178.250070.40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12989-021-00404-3","article-title":"Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19","volume":"18","author":"Li","year":"2021","journal-title":"Part Fibre Toxicol"},{"key":"2025100801300731000_34.178.250070.41","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.3390\/ijerph20054393","article-title":"Effects of PM2.5 exposure on the ACE\/ACE2 pathway: possible implication in COVID-19 pandemic","volume":"20","author":"Botto","year":"2023","journal-title":"Int J Environ Res Public Health"},{"key":"2025100801300731000_34.178.250070.42","doi-asserted-by":"crossref","first-page":"335","DOI":"10.24272\/j.issn.2095-8137.2021.088","article-title":"Particulate matter exposure exacerbates susceptibility to SARS-CoV-2 infection in humanized ACE2 mice","volume":"42","author":"Zhu","year":"2021","journal-title":"Zool Res"},{"key":"2025100801300731000_34.178.250070.43","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/s41598-022-04906-8","article-title":"Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2","volume":"12","author":"Vo","year":"2022","journal-title":"Sci Rep"},{"key":"2025100801300731000_34.178.250070.44","doi-asserted-by":"crossref","first-page":"560","DOI":"10.3390\/toxics12080560","article-title":"Correlation between exposure to UFP and ACE\/ACE2 pathway: looking for possible involvement in COVID-19 pandemic","volume":"12","author":"Botto","year":"2024","journal-title":"Toxics"},{"key":"2025100801300731000_34.178.250070.45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12989-024-00601-w","article-title":"Diesel exhaust particle inhalation in conjunction with high-fat diet consumption alters the expression of pulmonary SARS-COV-2 infection pathways, which is mitigated by probiotic treatment in C57BL\/6 male mice","volume":"21","author":"Nguyen-Alley","year":"2024","journal-title":"Part Fibre Toxicol"},{"key":"2025100801300731000_34.178.250070.46","doi-asserted-by":"crossref","first-page":"101312","DOI":"10.1016\/j.genrep.2021.101312","article-title":"Systems level insights into the impact of airborne exposure on SARS-CoV-2 pathogenesis and COVID-19 outcome \u2013 a multi-omics big data study","volume":"25","author":"Manivannan","year":"2021","journal-title":"Gene Rep"},{"key":"2025100801300731000_34.178.250070.47","first-page":"119","article-title":"Joint impact of key air pollutants on COVID-19 severity: prediction based on toxicogenomic data analysis","volume":"73","author":"\u0110uki\u0107-\u0106osi\u0107","year":"2022","journal-title":"Arh Hig Rada Toksikol"},{"key":"2025100801300731000_34.178.250070.48","first-page":"91","article-title":"Correlation of expression of MMP-2, ACE2, and TMPRSS2 genes with lymphopenia for mild and severity of COVID-19","volume":"22","author":"Ghezelbash","year":"2023","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"2025100801300731000_34.178.250070.49","doi-asserted-by":"crossref","first-page":"12622","DOI":"10.3390\/ijerph191912622","article-title":"Association of ACE2 gene variants with the severity of COVID-19 disease-a prospective observational study","volume":"19","author":"Sienko","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"2025100801300731000_34.178.250070.50","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/HJH.0000000000003054","article-title":"A low aldosterone\/renin ratio and high soluble ACE2 associate with COVID-19 severity","volume":"40","author":"Akin","year":"2022","journal-title":"J Hypertens"},{"key":"2025100801300731000_34.178.250070.51","doi-asserted-by":"crossref","first-page":"836516","DOI":"10.3389\/fimmu.2022.836516","article-title":"ACE2 serum levels as predictor of infectability and outcome in COVID-19","volume":"13","author":"Maza","year":"2022","journal-title":"Front Immunol"},{"key":"2025100801300731000_34.178.250070.52","doi-asserted-by":"crossref","first-page":"170717","DOI":"10.1016\/j.peptides.2021.170717","article-title":"ACE2 suppresses the inflammatory response in LPS-induced porcine intestinal epithelial cells via regulating the NF-\u03baB and MAPK pathways","volume":"149","author":"Li","year":"2022","journal-title":"Peptides"},{"key":"2025100801300731000_34.178.250070.53","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10311-020-01091-w","article-title":"Air pollution by NO2 and PM2.5 explains COVID-19 infection severity by overexpression of angiotensin-converting enzyme 2 in respiratory cells: a review","volume":"19","author":"Paital","year":"2021","journal-title":"Environ Chem Lett"},{"key":"2025100801300731000_34.178.250070.54","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"2025100801300731000_34.178.250070.55","doi-asserted-by":"crossref","first-page":"832394","DOI":"10.3389\/fimmu.2022.832394","article-title":"The role of cytokines and chemokines in severe acute respiratory syndrome coronavirus 2 infections","volume":"13","author":"Hsu","year":"2022","journal-title":"Front Immunol"},{"key":"2025100801300731000_34.178.250070.56","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26232"},{"key":"2025100801300731000_34.178.250070.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0968-3"},{"key":"2025100801300731000_34.178.250070.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38682-4"},{"key":"2025100801300731000_34.178.250070.59","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3390\/idr16040042","article-title":"Persistent vascular complications in long COVID: the role of ACE2 deactivation, microclots, and uniform fibrosis","volume":"16","author":"Sideratou","year":"2024","journal-title":"Infect Dis Rep"},{"key":"2025100801300731000_34.178.250070.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2017.06.014"},{"key":"2025100801300731000_34.178.250070.61","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0100OC"},{"key":"2025100801300731000_34.178.250070.62","doi-asserted-by":"crossref","first-page":"115148","DOI":"10.1016\/j.envpol.2020.115148","article-title":"Particulate matter (PM10) enhances RNA virus infection through modulation of innate immune responses","volume":"266","author":"Mishra","year":"2020","journal-title":"Environ Pollut"}],"container-title":["European Respiratory Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/16000617.0070-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:30:22Z","timestamp":1759912222000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/16000617.0070-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":62,"journal-issue":{"issue":"178","published-online":{"date-parts":[[2025,10,8]]},"published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1183\/16000617.0070-2025"],"URL":"https:\/\/doi.org\/10.1183\/16000617.0070-2025","relation":{},"ISSN":["0905-9180","1600-0617"],"issn-type":[{"value":"0905-9180","type":"print"},{"value":"1600-0617","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]}}}