학술논문
Immunologic resilience and COVID-19 survival advantage
Document Type
article
Author
Lee, Grace C; Restrepo, Marcos I; Harper, Nathan; Manoharan, Muthu Saravanan; Smith, Alisha M; Meunier, Justin A; Sanchez-Reilly, Sandra; Ehsan, Aamir; Branum, Anne P; Winter, Caitlyn; Winter, Lauryn; Jimenez, Fabio; Pandranki, Lavanya; Carrillo, Andrew; Perez, Graciela L; Anzueto, Antonio; Trinh, Hanh; Lee, Monica; Hecht, Joan M; Martinez-Vargas, Celida; Sehgal, Raj T; Cadena, Jose; Walter, Elizabeth A; Oakman, Kimberly; Benavides, Raymond; Pugh, Jacqueline A; Team, South Texas Veterans Health Care System COVID-19; Abdalla, Mohamed I; Adams, Sandra G; Agnew, Joseph; Ali, Saleem; Barker, Jennifer; Birdwell, Angela; Bradford, Stephen; Briggs, Heather; Corral, Judith Marin; Dacus, Jennifer J; Danaher, Patrick J; DePaul, Scott A; Dickerson, Jill; Doanne, Jollynn; Elbel, Samantha; Escamilla, Corina; Farrar, Robert; Feldman, David; Flynn, Julianne; Ford, Delvina; Foy, Joanna D; Freeman, Megan; Galley, Samantha; Garza, Maritza; Gilman, Sherraine; Gomez, Jennifer; Goyal, Varun K; Grassmuck, Sally; Hanson, Joshua; Harris, Brande; Hastings, Gabrielyd; Haywood, Audrey; Hinojosa, Cecilia; Ho, Tony T; Hopkins, Teri; Jewell, Pamela; Johnson, Thomas B; Kotogiannes, Vasiliki; Lawler, Austin C; Lester, Chadwick S; Levine, Stephanie M; Lewis, Haidee V; Louder, Angel; Mainor, Charmaine; Maldonado, Rachel; Martinez, Yvette; McElligott, Neil; Medlin, Laura; Mireles, Myra; Morneau, Kathleen; Munro, Samuel B; Nambiar, Anoop; Nassery, Daniel; Nathanson, Robert; O’Rorke, Jane; Padgett, Cheryl; Pascual-Guardia, Sergi; Patterson, Marisa; Perez, Rogelio; Phillips, Robert E; Polk, Patrick B; Pomager, Michael A; Preston, Kristy J; Proud, Kevin C; Rangel, Michelle; Ratcliffe, Temple A; Reichelderfer, Renee L; Renz, Evan M; Ross, Jeanette; Rudd, Teresa; Sanchez, Maria E; Sanders, Tammy; Schindler, Kevin C
Source
Journal of Allergy and Clinical Immunology. 148(5)
Subject
Language
Abstract
BackgroundThe risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR).ObjectiveWe sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality.MethodsIR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes.ResultsIHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females.ConclusionsPreservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.