Immunologic resilience and COVID-19 survival advantage.
J Allergy Clin Immunol
; 148(5): 1176-1191, 2021 11.
Article
in English
| MEDLINE | ID: covidwho-1401557
ABSTRACT
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory Insufficiency
/
T-Lymphocytes
/
HIV Infections
/
Sex Factors
/
HIV-1
/
SARS-CoV-2
/
COVID-19
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
North America
Language:
English
Journal:
J Allergy Clin Immunol
Year:
2021
Document Type:
Article
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