{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:27:57Z","timestamp":1786116477210,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R21ES032739"],"award-info":[{"award-number":["R21ES032739"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P42ES027725"],"award-info":[{"award-number":["P42ES027725"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R21ES032739"],"award-info":[{"award-number":["R21ES032739"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P42ES027725"],"award-info":[{"award-number":["P42ES027725"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Since emerging in late 2019, SARS-CoV-2 has caused over 7 million deaths globally and remains a public health concern. Understanding SARS-CoV-2 pathogenesis is vital, especially as factors like environmental exposures are still poorly understood. Polycyclic aromatic hydrocarbons (PAHs), like benzo[a]pyrene (BP), found in pollutants like cigarette smoke, diesel exhaust, and charcoal-broiled steaks, are known to injure the lungs. We aimed to evaluate if BP exacerbates SARS-CoV-2 pathogenesis in a mouse model of disease. One day following intranasal administration of BP (20 mg\/kg) or vehicle control, we infected male and female K18-hACE2 mice with ancestral SARS-CoV-2 and assessed lung viral load, weight change, clinical scores, immune cell recruitment, and survival in the presence and absence of BP exposure. We found that BP-exposed mice had decreased survival compared to mock-exposed mice. Additionally, BP did not alter innate or adaptive immune cell populations in the lungs of SARS-CoV-2-infected mice. These findings suggest that PAH exposure exacerbates severe COVID-19 outcomes by unknown mechanisms, highlighting the need to further explore environmental impacts on SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/v18080823","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Environmental Polycyclic Aromatic Hydrocarbon (PAH) Benzo[a]pyrene (BP) Alters SARS-CoV-2 Pathogenesis in a Mouse Model of Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Jennifer L.","family":"Spencer Clinton","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"William T Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7262-0063","authenticated-orcid":false,"given":"Freedom M.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"William T Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma E.","family":"Crotty","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Critical Care, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-2874","authenticated-orcid":false,"given":"Yike","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Strobel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"William T Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2034-2625","authenticated-orcid":false,"given":"Fong W.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Critical Care, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagavatula","family":"Moorthy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E.","family":"Ronca","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"William T Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, June 24). WHO COVID-19 Dashboard. Available online: https:\/\/data.who.int\/dashboards\/covid19\/cases."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/10937404.2022.2164390","article-title":"Polycyclic aromatic hydrocarbons (PAHs): Updated aspects of their determination, kinetics in the human body, and toxicity","volume":"26","author":"Barbosa","year":"2023","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1289\/ehp.6895","article-title":"Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: A review and meta-analysis","volume":"112","author":"Armstrong","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133948","DOI":"10.1016\/j.chemosphere.2022.133948","article-title":"Polycyclic aromatic hydrocarbon and its effects on human health: An overeview","volume":"296","author":"Mallah","year":"2022","journal-title":"Chemosphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114465","DOI":"10.1016\/j.envpol.2020.114465","article-title":"Can atmospheric pollution be considered a co-factor in extremely high level of SARS-CoV-2 lethality in Northern Italy?","volume":"261","author":"Conticini","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"138401","DOI":"10.1016\/j.scitotenv.2020.138401","article-title":"A field indoor air measurement of SARS-CoV-2 in the patient rooms of the largest hospital in Iran","volume":"725","author":"Faridi","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"138540","DOI":"10.1016\/j.scitotenv.2020.138540","article-title":"Changes in air quality during the lockdown in Barcelona (Spain) one month into the SARS-CoV-2 epidemic","volume":"726","author":"Carnerero","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.18332\/tid\/119324","article-title":"COVID-19 and smoking: A systematic review of the evidence","volume":"18","author":"Vardavas","year":"2020","journal-title":"Tob. Induc. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/ntr\/ntac085","article-title":"Active Smokers Are at Higher Risk of COVID-19 Death: A Systematic Review and Meta-analysis","volume":"25","author":"Patanavanich","year":"2023","journal-title":"Nicotine Tob. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1136\/thoraxjnl-2021-217080","article-title":"Smoking and COVID-19 outcomes: An observational and Mendelian randomisation study using the UK Biobank cohort","volume":"77","author":"Clift","year":"2022","journal-title":"Thorax"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/joim.13190","article-title":"Tobacco smoking confers risk for severe COVID-19 unexplainable by pulmonary imaging","volume":"289","author":"Li","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"619523","DOI":"10.1155\/2013\/619523","article-title":"Contribution of lung macrophages to the inflammatory responses induced by exposure to air pollutants","volume":"2013","author":"Hiraiwa","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.tox.2009.01.028","article-title":"Cytokine and chemokine expression patterns in lung epithelial cells exposed to components characteristic of particulate air pollution","volume":"259","author":"Ovrevik","year":"2009","journal-title":"Toxicology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142256","DOI":"10.1016\/j.chemosphere.2024.142256","article-title":"Viral respiratory infections and air pollution: A review focused on research in Poland","volume":"359","author":"Rzymski","year":"2024","journal-title":"Chemosphere"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.116.309279","article-title":"Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation","volume":"119","author":"Pope","year":"2016","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45666","DOI":"10.1038\/srep45666","article-title":"Exposure to Ambient Particulate Matter Induced COPD in a Rat Model and a Description of the Underlying Mechanism","volume":"7","author":"He","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2400133","DOI":"10.1183\/13993003.00133-2024","article-title":"Smoking and vaping alter genes related to mechanisms of SARS-CoV-2 susceptibility and severity: A systematic review and meta-analysis","volume":"64","author":"Bowsher","year":"2024","journal-title":"Eur. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s11684-021-0837-6","article-title":"Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells","volume":"15","author":"Wang","year":"2021","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"633","DOI":"10.15585\/mmwr.mm7329a1","article-title":"Adult Smoking Cessation\u2014United States, 2022","volume":"73","author":"VanFrank","year":"2024","journal-title":"Morb. Mortal. Wkly. Rep. (MMWR)"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1016\/S2213-2600(20)30117-X","article-title":"Sex difference and smoking predisposition in patients with COVID-19","volume":"8","author":"Cai","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1007\/s10067-020-05073-9","article-title":"Rheumatologists\u2019 perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets","volume":"39","author":"Misra","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0140-6736(20)30260-9","article-title":"Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: A modelling study","volume":"395","author":"Wu","year":"2020","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Harcourt, J., Tamin, A., Lu, X., Kamili, S., Sakthivel, S.K., Murray, J., Queen, K., Tao, Y., Paden, C.R., and Zhang, J. (2020). Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient. bioRxiv.","DOI":"10.1101\/2020.03.02.972935"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41586-020-2312-y","article-title":"The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice","volume":"583","author":"Bao","year":"2020","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1007\/s00267-022-01743-3","article-title":"Environmental Impacts of Hurricane Harvey on the Neches-Brakes Bayou River System in Beaumont, Texas","volume":"71","author":"Rao","year":"2023","journal-title":"Environ. Manag."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1093\/jn\/134.8.2011","article-title":"Development of a food database of nitrosamines, heterocyclic amines, and polycyclic aromatic hydrocarbons","volume":"134","author":"Jakszyn","year":"2004","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1383-5742(99)00016-2","article-title":"Polycyclic aromatic hydrocarbons in the diet","volume":"443","author":"Phillips","year":"1999","journal-title":"Mutat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.taap.2011.09.020","article-title":"Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents","volume":"257","author":"Crowell","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/toxsci\/kft124","article-title":"Impact of pregnancy on the pharmacokinetics of dibenzo[def,p]chrysene in mice","volume":"135","author":"Crowell","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lam, F.W., Brown, C.A., and Ronca, S.E. (2024). Recombinant Rod Domain of Vimentin Reduces SARS-CoV-2 Viral Replication by Blocking Spike Protein-ACE2 Interactions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052477"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.4049\/jimmunol.1700784","article-title":"Recombinant Human Vimentin Binds to P-Selectin and Blocks Neutrophil Capture and Rolling on Platelets and Endothelium","volume":"200","author":"Lam","year":"2018","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1165\/rcmb.2009-0210ST","article-title":"An official American Thoracic Society workshop report: Features and measurements of experimental acute lung injury in animals","volume":"44","author":"Downey","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2300834","DOI":"10.1002\/advs.202300834","article-title":"Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression","volume":"10","author":"Liu","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e28962","DOI":"10.1002\/jmv.28962","article-title":"Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study","volume":"95","author":"Rzymski","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41591-020-0901-9","article-title":"Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19","volume":"26","author":"Liao","year":"2020","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.immuni.2020.05.002","article-title":"Immunology of COVID-19: Current State of the Science","volume":"52","author":"Vabret","year":"2020","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17718","DOI":"10.1038\/s41598-020-73955-8","article-title":"Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients","volume":"10","author":"Liu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"198464","DOI":"10.1016\/j.virusres.2021.198464","article-title":"Immune characterization and profiles of SARS-CoV-2 infected patients reveals potential host therapeutic targets and SARS-CoV-2 oncogenesis mechanism","volume":"301","author":"Policard","year":"2021","journal-title":"Virus Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41591-020-0819-2","article-title":"Breadth of concomitant immune responses prior to patient recovery: A case report of non-severe COVID-19","volume":"26","author":"Thevarajan","year":"2020","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/S2213-2600(22)00182-5","article-title":"Tobacco product use and the risks of SARS-CoV-2 infection and COVID-19: Current understanding and recommendations for future research","volume":"10","author":"Benowitz","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Goedtke, L., Sprenger, H., Hofmann, U., Schmidt, F.F., Hammer, H.S., Zanger, U.M., Poetz, O., Seidel, A., Braeuning, A., and Hessel-Pras, S. (2020). Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010372"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/823\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:50:30Z","timestamp":1786009830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/823"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,26]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["v18080823"],"URL":"https:\/\/doi.org\/10.3390\/v18080823","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,26]]}}}