TY - JOUR
T1 - Immunologic resilience and COVID-19 survival advantage
AU - South Texas Veterans Health Care System COVID-19 Team
AU - Lee, Grace C.
AU - Restrepo, Marcos I.
AU - Harper, Nathan
AU - Manoharan, Muthu Saravanan
AU - Smith, Alisha M.
AU - Meunier, Justin A.
AU - Sanchez-Reilly, Sandra
AU - Ehsan, Aamir
AU - Branum, Anne P.
AU - Winter, Caitlyn
AU - Winter, Lauryn
AU - Jimenez, Fabio
AU - Pandranki, Lavanya
AU - Carrillo, Andrew
AU - Perez, Graciela L.
AU - Anzueto, Antonio
AU - Trinh, Hanh
AU - Lee, Monica
AU - Hecht, Joan M.
AU - Martinez-Vargas, Celida
AU - Sehgal, Raj T.
AU - Cadena, Jose
AU - Walter, Elizabeth A.
AU - Oakman, Kimberly
AU - Benavides, Raymond
AU - Pugh, Jacqueline A.
AU - Abdalla, Mohamed I.
AU - Adams, Sandra G
AU - Agnew, Joseph
AU - Briggs, Heather
AU - DePaul, Scott A.
AU - Goyal, Varun K.
AU - Haywood, Audrey
AU - Ho, Tony T.
AU - Levine, Stephanie M.
AU - Nambiar, Anoop
AU - Nathanson, Robert
AU - O'Rorke, Jane
AU - Proud, Kevin C.
AU - Ratcliffe, Temple A.
AU - Schindler, Kevin C.
AU - Soni, Nilam
AU - Venticinque, Steven G.
AU - Trammell Velasquez, Sadie A.
AU - Moreira, Alvaro G.
AU - Zhang, Nu
AU - Leadbetter, Elizabeth
AU - He, Weijing
AU - Clark, Robert A.
AU - Ahuja, Sunil K.
N1 - Publisher Copyright:
© 2021
PY - 2021/11
Y1 - 2021/11
N2 - Background: The 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). Objective: We 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. Methods: IR 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. Results: IHG-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. Conclusions: Preservation 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.
AB - Background: The 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). Objective: We 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. Methods: IR 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. Results: IHG-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. Conclusions: Preservation 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.
KW - AIDS
KW - Aging
KW - COVID-19
KW - HIV
KW - SARS-CoV-2
KW - biomarkers
KW - immune
KW - inflammation
KW - influenza
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U2 - 10.1016/j.jaci.2021.08.021
DO - 10.1016/j.jaci.2021.08.021
M3 - Article
C2 - 34508765
AN - SCOPUS:85117853558
SN - 0091-6749
VL - 148
SP - 1176
EP - 1191
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -