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dc.contributor.authorSilverstein, Noah J.
dc.contributor.authorWang, Yetao
dc.contributor.authorCarbone, Claudia
dc.contributor.authorDauphin, Ann
dc.contributor.authorLuban, Jeremy
dc.date2022-08-11T08:08:11.000
dc.date.accessioned2022-08-23T15:45:37Z
dc.date.available2022-08-23T15:45:37Z
dc.date.issued2022-03-11
dc.date.submitted2022-03-31
dc.identifier.citation<p>Silverstein NJ, Wang Y, Manickas-Hill Z, Carbone C, Dauphin A, Boribong BP, Loiselle M, Davis J, Leonard MM, Kuri-Cervantes L; MGH COVID-19 Collection & Processing Team, Meyer NJ, Betts MR, Li JZ, Walker BD, Yu XG, Yonker LM, Luban J. Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection. Elife. 2022 Mar 11;11:e74681. doi: 10.7554/eLife.74681. Epub ahead of print. PMID: 35275061. <a href="https://doi.org/10.7554/eLife.74681">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.74681
dc.identifier.pmid35275061
dc.identifier.urihttp://hdl.handle.net/20.500.14038/27568
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractBackground: Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations. Methods: Multiple regression was used to determine the relationship between abundance of specific blood lymphoid cell types, age, sex, requirement for hospitalization, duration of hospitalization, and elevation of blood markers of systemic inflammation, in adults hospitalized for severe COVID-19 (n=40), treated for COVID-19 as outpatients (n=51), and in uninfected controls (n=86), as well as in children with COVID-19 (n=19), recovering from COVID-19 (n=14), MIS-C (n=11), recovering from MIS-C (n=7), and pediatric controls (n=17). Results: This observational study found that the abundance of innate lymphoid cells (ILCs) decreases more than 7-fold over the human lifespan - T cell subsets decrease less than 2-fold - and is lower in males than in females. After accounting for effects of age and sex, ILCs, but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, the abundance of ILCs, but not of T cells, correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and the numbers of these cells did not recover during follow-up. In contrast, children with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked closely with ILCs from lung. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis. Among controls, the percentage of ILCs that produced amphiregulin was higher in females than in males, and people hospitalized with COVID-19 had a lower percentage of ILCs that produced amphiregulin than did controls. Conclusions: These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance contributes to increased COVID-19 severity with age and in males. Funding: This work was supported in part by the Massachusetts Consortium for Pathogen Readiness and NIH grants R37AI147868, R01AI148784, F30HD100110, 5K08HL143183.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=35275061&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2022, Silverstein et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjecthuman
dc.subjectimmunology
dc.subjectinflammation
dc.subjectmedicine
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectInfectious Disease
dc.subjectMicrobiology
dc.subjectVirus Diseases
dc.titleInnate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection
dc.typeAccepted Manuscript
dc.source.journaltitleeLife
dc.source.volume11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1377&amp;context=covid19&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/covid19/369
dc.identifier.contextkey28457064
refterms.dateFOA2022-08-23T15:45:37Z
html.description.abstract<p>Background: Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations.</p> <p>Methods: Multiple regression was used to determine the relationship between abundance of specific blood lymphoid cell types, age, sex, requirement for hospitalization, duration of hospitalization, and elevation of blood markers of systemic inflammation, in adults hospitalized for severe COVID-19 (n=40), treated for COVID-19 as outpatients (n=51), and in uninfected controls (n=86), as well as in children with COVID-19 (n=19), recovering from COVID-19 (n=14), MIS-C (n=11), recovering from MIS-C (n=7), and pediatric controls (n=17).</p> <p>Results: This observational study found that the abundance of innate lymphoid cells (ILCs) decreases more than 7-fold over the human lifespan - T cell subsets decrease less than 2-fold - and is lower in males than in females. After accounting for effects of age and sex, ILCs, but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, the abundance of ILCs, but not of T cells, correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and the numbers of these cells did not recover during follow-up. In contrast, children with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked closely with ILCs from lung. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis. Among controls, the percentage of ILCs that produced amphiregulin was higher in females than in males, and people hospitalized with COVID-19 had a lower percentage of ILCs that produced amphiregulin than did controls.</p> <p>Conclusions: These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance contributes to increased COVID-19 severity with age and in males.</p> <p>Funding: This work was supported in part by the Massachusetts Consortium for Pathogen Readiness and NIH grants R37AI147868, R01AI148784, F30HD100110, 5K08HL143183.</p>
dc.identifier.submissionpathcovid19/369
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentSchool of Medicine
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pagese74681


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© 2022, Silverstein et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as © 2022, Silverstein et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.