Immunologic resilience and COVID-19 survival advantage.
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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, South Texas Veterans Health Care System COVID-19 Team, Letendre Scott, Steri Maristella, Orrù Valeria, Fiorillo Edoardo, Cucca Francesco, Moreira Alvaro G, Zhang Nu, Leadbetter Elizabeth, Agan Brian K, Richman Douglas D, He Weijing, Clark Robert A, Okulicz Jason F, Ahuja Sunil K
Аннотация
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.