Biomarkers of immunological resilience predict both COVID-19 severity and longevity
Published: September 7, 2021
The reasons why persons of similar ages vary in their susceptibility to progressive COVID-19, characterized by hospitalization, respiratory failure, delayed clearance of virus from the airways, and death, are unclear. While the risk of progressive COVID-19 increases with age, some older persons resist progression, manifesting asymptomatic or mild (i.e., nonprogressive) COVID-19; conversely, some younger persons manifest progressive COVID-19. Females appear to resist progressive COVID-19 better than males, aligning with the observation that females manifest features of superior immunocompetence, including resistance to some infections and longer lifespans. Thus, it is conceivable that, among persons of similar ages, susceptibility to progressive COVID-19 relates to a deficit in an attribute that optimizes immunity against infections and extends lifespan. This deficit may antedate or arise in response to SARS-CoV-2 infection; additionally, males may be more prone to develop this deficit.
In a recent issue of The Journal of Allergy and Clinical Immunology (JACI), Lee et al introduce the novel concept of immunologic resilience (IR), defined as the capacity to preserve or restore immune competence and control inflammation in the face of infection or other antigenic challenges. In a prospective study of 522 veterans with COVID-19, IR was monitored through immune health grades (IHGs). In hospitalized patients, IR metrics were monitored daily. The four IHGs (I [highest level] to IV) track distinct levels of equilibrium or disequilibrium between blood counts of the immune-supporting CD4+ and CD8+ T-cells. Gene expression profiles in the blood that differentiated persons with vs. without progressive COVID-19 were also used to monitor IR. For comparative purposes, the researchers evaluated IR metrics in cohorts without COVID-19 comprising 13,461 individuals.
In otherwise healthy persons without COVID-19, IHG-I was the most prevalent grade across all age ranges, especially in females. In contrast, among untreated HIV-seropositive persons, IHG-IV was the most common grade, and IHG-I vs. IHG-IV was associated with the lowest vs highest risk of developing AIDS, respectively. Congruent with these observations in HIV-seropositive patients, among COVID-19 patients of similar ages, a nonprogressive disease course was observed in individuals who presented with IHG-I versus grades marked by lower CD4+ T-cell counts (IHG-II and IHG-IV). During COVID-19, presentation with IHG-I was more common in females. Gene expression profiles tracking higher immune competence and lower inflammation associated with survival during both COVID-19 and natural aging. These longevity-associated gene expression profiles were more commonly observed in females and in persons with IHG-I. During convalescence, COVID-19 patients appeared to restore the grade that may have antedated COVID-19.
Females resist degradation of IR, including during COVID-19. This resistance associates with longevity. The level of IR at COVID-19 presentation prognosticates risk of progressive disease, irrespective of age. Thus, IR metrics have value for precision immune health monitoring across the life span, irrespective of COVID-19 status.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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