{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:54:42Z","timestamp":1778172882632,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Type 2 immune responses are characterized by elevated type 2 cytokines and blood eosinophilia. Emerging evidence suggests that people with chronic type 2 inflammatory lung diseases are not particularly susceptible to SARS-CoV-2 infection. Intriguingly, recent in vitro, ex vivo research demonstrates type 2 cytokines, particularly IL-13, reduce the risk of SARS-CoV-2 infection in the airway epithelium. IL-13 treatment in airway epithelial cells followed by SARS-CoV-2 diminished viral entry, replication, spread, and cell death. IL-13 reduces the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in the airway epithelium and transmembrane serine protease 2 (TMPRSS2), particularly in ciliated cells. It also alters the cellular composition toward a secretory-cell-rich phenotype reducing total ciliated cells and, thus, reducing viral tropism. IL-13 enhances Muc5ac mucin and glycocalyx secretion in the periciliary layer, which acts as a physical barrier to restrict virus attachment. Moreover, type 2 airway immune cells, such as M2 alveolar macrophages, CD4+ tissue-resident memory T cells, and innate lymphoid 2 cells, may also rescue type 2 airways from SARS-CoV-2-induced adverse effects. In this review, we discuss recent findings that demonstrate how type 2 immunity alters immune responses against SARS-CoV-2 and its consequences on COVID-19 pathogenesis.<\/jats:p>","DOI":"10.3390\/v15020402","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T03:22:47Z","timestamp":1675221767000},"page":"402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Type 2 Immunity and Its Impact on COVID-19 Infection in the Airways"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4947-5918","authenticated-orcid":false,"given":"Prabuddha S.","family":"Pathinayake","sequence":"first","affiliation":[{"name":"School of Medicine and Public Health, The University of Newcastle and Immune Health Program Hunter Medical Research Institute, Newcastle, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil T.","family":"Awatade","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, The University of Newcastle and Immune Health Program Hunter Medical Research Institute, Newcastle, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A. B.","family":"Wark","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, The University of Newcastle and Immune Health Program Hunter Medical Research Institute, Newcastle, NSW 2308, Australia"},{"name":"Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jaci.2016.06.033","article-title":"Interleukins (from IL-1 to IL-38), interferons, transforming growth factor \u03b2, and TNF-\u03b1: Receptors, functions, and roles in diseases","volume":"138","author":"Akdis","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/S0140-6736(15)00157-9","article-title":"Targeting the interleukin pathway in the treatment of asthma","volume":"386","author":"Chung","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The Cytokines of Asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jaci.2015.05.052","article-title":"Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes","volume":"136","author":"Barnes","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jaci.2015.01.021","article-title":"TH9 cells are required for tissue mast cell accumulation during allergic inflammation","volume":"136","author":"Sehra","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.3389\/fphar.2019.01387","article-title":"The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma","volume":"10","author":"Marone","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/WOX.0b013e31821188e0","article-title":"Interleukin-13 signaling and its role in asthma","volume":"4","author":"Rael","year":"2011","journal-title":"World Allergy Organ. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1146\/annurev.med.53.082901.103921","article-title":"The pathophysiology of asthma","volume":"53","author":"Maddox","year":"2002","journal-title":"Annu. Rev. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"797","DOI":"10.3349\/ymj.2010.51.6.797","article-title":"Mast cells in allergic asthma and beyond","volume":"51","author":"Reuter","year":"2010","journal-title":"Yonsei Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature07204","article-title":"The development of allergic inflammation","volume":"454","author":"Galli","year":"2008","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1084\/jem.20041901","article-title":"Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus","volume":"201","author":"Wark","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1136\/thoraxjnl-2011-200708","article-title":"Impaired type I and III interferon response to rhinovirus infection during pregnancy and asthma","volume":"67","author":"Forbes","year":"2012","journal-title":"Thorax"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gomez, J.L., Diaz, M.P., Nino, G., and Britto, C.J. (2018). Impaired type I interferon regulation in the blood transcriptome of recurrent asthma exacerbations. BMC Med. Genom., 11.","DOI":"10.1186\/s12920-018-0340-3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/mi.2012.118","article-title":"Impaired innate interferon induction in severe therapy resistant atopic asthmatic children","volume":"6","author":"Edwards","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/all.12627","article-title":"Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells","volume":"70","author":"Contoli","year":"2015","journal-title":"Allergy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jaci.2014.11.039","article-title":"Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons","volume":"136","author":"Gielen","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s12016-016-8548-5","article-title":"Bacterial and Viral Infections in Atopic Dermatitis: A Comprehensive Review","volume":"51","author":"Ong","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1007\/s40520-020-01631-y","article-title":"COVID-19 and the elderly: Insights into pathogenesis and clinical decision-making","volume":"32","author":"Perrotta","year":"2020","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2001875","DOI":"10.1183\/13993003.01875-2020","article-title":"Characteristics and outcomes of asthmatic patients with COVID-19 pneumonia who require hospitalisation","volume":"56","author":"Beurnier","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e148517","DOI":"10.1172\/JCI148517","article-title":"Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19","volume":"131","author":"Ahn","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S2213-2600(20)30193-4","article-title":"Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: An analysis in ex-vivo and in-vitro cultures","volume":"8","author":"Hui","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1056\/NEJMicm2023328","article-title":"SARS-CoV-2 Infection of Airway Cells","volume":"383","author":"Ehre","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2119680119","DOI":"10.1073\/pnas.2119680119","article-title":"SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13","volume":"119","author":"Morrison","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","article-title":"Structural basis of receptor recognition by SARS-CoV-2","volume":"581","author":"Shang","year":"2020","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1021\/acscentsci.0c01537","article-title":"CD209L\/L-SIGN and CD209\/DC-SIGN Act as Receptors for SARS-CoV-2","volume":"7","author":"Amraei","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"ref_27","unstructured":"Mori, Y., Fink, C., Ichimura, T., Sako, K., Mori, M., Lee, N.N., Aschauer, P., Padmanabha Das, K.M., Hong, S., and Song, M. (2022). KIM-1\/TIM-1 is a Receptor for SARS-CoV-2 in Lung and Kidney. medRxiv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41422-020-00460-y","article-title":"AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells","volume":"31","author":"Wang","year":"2021","journal-title":"Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41392-020-00426-x","article-title":"CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells","volume":"5","author":"Wang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: Implications for SARS-CoV-2","volume":"19","author":"Kratzel","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jaci.2020.05.051","article-title":"Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype","volume":"146","author":"Camiolo","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/resp.14003","article-title":"ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma","volume":"26","author":"Wark","year":"2021","journal-title":"Respirology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1007\/s00405-020-06408-7","article-title":"ACE2 expression in allergic airway disease may decrease the risk and severity of COVID-19","volume":"278","year":"2021","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jaci.2020.05.004","article-title":"Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells","volume":"146","author":"Kimura","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jaci.2020.04.009","article-title":"Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2","volume":"146","author":"Jackson","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jaci.2020.05.013","article-title":"ACE2, TMPRSS2, and furin gene expression in the airways of people with asthma-implications for COVID-19","volume":"146","author":"Bradding","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/mi.2012.81","article-title":"Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways","volume":"6","author":"Kesimer","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1165\/rcmb.2021-0364OC","article-title":"The Type 2 Asthma Mediator IL-13 Inhibits Severe Acute Respiratory Syndrome Coronavirus 2 Infection of Bronchial Epithelium","volume":"66","author":"Bonser","year":"2022","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/mi.2012.74","article-title":"The alveolar macrophages in asthma: A double-edged sword","volume":"5","author":"Balhara","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1136\/thoraxjnl-2015-207020","article-title":"Pulmonary macrophages: Key players in the innate defence of the airways","volume":"70","author":"Byrne","year":"2015","journal-title":"Thorax"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lee, J.W., Chun, W., Lee, H.J., Min, J.H., Kim, S.M., Seo, J.Y., Ahn, K.S., and Oh, S.R. (2021). The Role of Macrophages in the Development of Acute and Chronic Inflammatory Lung Diseases. Cells, 10.","DOI":"10.3390\/cells10040897"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-immunol-032712-095906","article-title":"Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: Roles in homeostasis and disease","volume":"31","author":"Locksley","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1165\/rcmb.2015-0295OC","article-title":"Alternative Macrophage Activation Is Increased in Asthma","volume":"55","author":"Girodet","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.jaci.2010.10.045","article-title":"More alternative activation of macrophages in lungs of asthmatic patients","volume":"127","author":"Melgert","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1084\/jem.20140825","article-title":"Alveolar macrophage\u2013derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes","volume":"212","author":"Goritzka","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"839585","DOI":"10.3389\/fmicb.2022.839585","article-title":"Modulation of Macrophage Polarization by Viruses: Turning Off\/On Host Antiviral Responses","volume":"13","author":"Yu","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"102734","DOI":"10.1016\/j.ebiom.2020.102734","article-title":"M1-like macrophages are potent producers of anti-viral interferons and M1-associated marker-positive lung macrophages are decreased during rhinovirus-induced asthma exacerbations","volume":"54","author":"Nikonova","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Matic, S., Popovic, S., Djurdjevic, P., Todorovic, D., Djordjevic, N., Mijailovic, Z., Sazdanovic, P., Milovanovic, D., Ruzic Zecevic, D., and Petrovic, M. (2020). SARS-CoV-2 infection induces mixed M1\/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241097"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1038\/s41467-022-29731-5","article-title":"Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model","volume":"13","author":"Lian","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hu, W., Song, X., Yu, H., Zhao, L., Zhao, Y., and Zhao, Y. (2021). Further comments on the role of ACE-2 positive macrophages in human lung. Cytom. A, 1\u20137.","DOI":"10.1002\/cyto.a.24484"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Song, X., Hu, W., Yu, H., Zhao, L., Zhao, Y., Zhao, X., Xue, H.H., and Zhao, Y. (2020). Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytom. A, 1\u201310.","DOI":"10.1002\/cyto.a.24285"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.immuni.2014.12.007","article-title":"Tissue-resident memory T cells","volume":"41","author":"Schenkel","year":"2014","journal-title":"Immunity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"616309","DOI":"10.3389\/fimmu.2021.616309","article-title":"The Role of CD4(+) Resident Memory T Cells in Local Immunity in the Mucosal Tissue\u2014Protection Versus Pathology","volume":"12","author":"Hirahara","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.4049\/jimmunol.1700257","article-title":"Biased Generation and In Situ Activation of Lung Tissue-Resident Memory CD4 T Cells in the Pathogenesis of Allergic Asthma","volume":"200","author":"Turner","year":"2018","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e20190865","DOI":"10.1084\/jem.20190865","article-title":"Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease","volume":"217","author":"Rahimi","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109.09","DOI":"10.4049\/jimmunol.208.Supp.109.09","article-title":"Cytotoxic CD4+ tissue-resident memory T cells are associated with asthma severity","volume":"208","author":"Mistry","year":"2022","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.4049\/jimmunol.1102243","article-title":"Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection","volume":"187","author":"Teijaro","year":"2011","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2014.09.007","article-title":"CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection","volume":"41","author":"Laidlaw","year":"2014","journal-title":"Immunity"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2000983","DOI":"10.1183\/13993003.00983-2020","article-title":"Lung CD4+ T-cells in patients with lung fibrosis produce pro-fibrotic interleukin-13 together with interferon-\u03b3","volume":"57","author":"Sikkeland","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.4049\/jimmunol.2100608","article-title":"Cutting Edge: Lung-Resident T Cells Elicited by SARS-CoV-2 Do Not Mediate Protection against Secondary Infection","volume":"207","author":"Roberts","year":"2021","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.alit.2018.11.001","article-title":"Airway innate lymphoid cells in the induction and regulation of allergy","volume":"68","author":"Doherty","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41423-020-00596-2","article-title":"Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment","volume":"18","author":"Spehner","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/ni.2131","article-title":"Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus","volume":"12","author":"Monticelli","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e1224","DOI":"10.1002\/cti2.1224","article-title":"Innate lymphoid cell composition associates with COVID-19 disease severity","volume":"9","author":"Kokkinou","year":"2020","journal-title":"Clin. Transl. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e74681","DOI":"10.7554\/eLife.74681","article-title":"Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection","volume":"11","author":"Silverstein","year":"2022","journal-title":"Elife"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1002\/eji.202149311","article-title":"SARS-CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10","volume":"51","author":"Gomes","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s10753-016-0467-3","article-title":"Association of interleukin-18 and asthma","volume":"40","author":"Xu","year":"2017","journal-title":"Inflammation"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lee, K.H., Gordon, A., Shedden, K., Kuan, G., Ng, S., Balmaseda, A., and Foxman, B. (2019). The respiratory microbiome and susceptibility to influenza virus infection. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0207898"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Harding, J.N., Siefker, D., Vu, L., You, D., DeVincenzo, J., Pierre, J.F., and Cormier, S.A. (2020). Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01816-5"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/cid\/ciz968","article-title":"Association Between the Respiratory Microbiome and Susceptibility to Influenza Virus Infection","volume":"71","author":"Tsang","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.immuni.2020.01.007","article-title":"The Role of Lung and Gut Microbiota in the Pathology of Asthma","volume":"52","author":"Barcik","year":"2020","journal-title":"Immunity"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.jaci.2016.10.046","article-title":"Eosinophilic airway inflammation in asthmatic patients is associated with an altered airway microbiome","volume":"140","author":"Sverrild","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1183\/13993003.00405-2015","article-title":"Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma","volume":"47","author":"Simpson","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jaci.2016.08.055","article-title":"Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment","volume":"140","author":"Durack","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.jaci.2015.05.044","article-title":"The airway microbiome in patients with severe asthma: Associations with disease features and severity","volume":"136","author":"Huang","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e0177721","DOI":"10.1128\/mBio.01777-21","article-title":"Signatures of COVID-19 Severity and Immune Response in the Respiratory Tract Microbiome","volume":"12","author":"Merenstein","year":"2021","journal-title":"MBio"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s40168-022-01342-8","article-title":"Alterations in the respiratory tract microbiome in COVID-19: Current observations and potential significance","volume":"10","author":"Merenstein","year":"2022","journal-title":"Microbiome"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1016\/j.jinf.2020.06.047","article-title":"The lung tissue microbiota features of 20 deceased patients with COVID-19","volume":"81","author":"Fan","year":"2020","journal-title":"J. Infect."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jinf.2020.05.046","article-title":"Co-infections in people with COVID-19: A systematic review and meta-analysis","volume":"81","author":"Lansbury","year":"2020","journal-title":"J. Infect."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Donlan, A.N., Sutherland, T.E., Marie, C., Preissner, S., Bradley, B.T., Carpenter, R.M., Sturek, J.M., Ma, J.Z., Moreau, G.B., and Donowitz, J.R. (2021). IL-13 is a driver of COVID-19 severity. MedRxiv.","DOI":"10.1172\/jci.insight.150107"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/all.14534","article-title":"Dupilumab, severe asthma airway responses, and SARS-CoV-2 serology","volume":"76","author":"Bhalla","year":"2021","journal-title":"Allergy"},{"key":"ref_85","first-page":"175","article-title":"Hyaluronan (HA) accumulation following SARS-CoV-2 infection and in non-resolvable COVID-19 fibrosis","volume":"8","author":"Peters","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e147472","DOI":"10.1172\/jci.insight.147472","article-title":"COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction","volume":"6","author":"Queisser","year":"2021","journal-title":"JCI Insight"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2101209","DOI":"10.1183\/13993003.01209-2021","article-title":"Asthma and COVID-19 risk: A systematic review and meta-analysis","volume":"59","author":"Sunjaya","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Parker, J.C., Thavagnanam, S., Skibinski, G., Lyons, J., Bell, J., Heaney, L.G., and Shields, M.D. (2013). Chronic IL9 and IL-13 exposure leads to an altered differentiation of ciliated cells in a well-differentiated paediatric bronchial epithelial cell model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061023"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1183\/09031936.05.00038605","article-title":"Severe asthma is an epithelial disease","volume":"25","author":"Chanez","year":"2005","journal-title":"Eur. Respir. J."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/2\/402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:27Z","timestamp":1760120367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/2\/402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,31]]},"references-count":89,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["v15020402"],"URL":"https:\/\/doi.org\/10.3390\/v15020402","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,31]]}}}