Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Immunologic resilience and COVID-19 survival advantage.

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.

Comparison of in-person versus tele-ultrasound point-of-care ultrasound training during the COVID-19 pandemic.

BACKGROUND: Lack of training is currently the most common barrier to implementation of point-of-care ultrasound (POCUS) use in clinical practice, and in-person POCUS continuing medical education (CME) courses have been paramount in improving this training gap. Due to travel restrictions and physical distancing requirements during the COVID-19 pandemic, most in-person POCUS training courses were cancelled. Though tele-ultrasound technology has existed for several years, use of tele-ultrasound technology to deliver hands-on training during a POCUS CME course has not been previously described. METHODS: We conducted a retrospective observational study comparing educational outcomes, course evaluations, and learner and faculty feedback from in-person versus tele-ultrasound POCUS courses. The same POCUS educational curriculum was delivered to learners by the two course formats. Data from the most recent pre-pandemic in-person course were compared to tele-ultrasound courses during the COVID-19 pandemic. RESULTS: Pre- and post-course knowledge test scores of learners from the in-person (n = 88) and tele-ultrasound course (n = 52) were compared. Though mean pre-course knowledge test scores were higher among learners of the tele-ultrasound versus in-person course (78% vs. 71%; p = 0.001), there was no significant difference in the post-course test scores between learners of the two course formats (89% vs. 87%; p = 0.069). Both learners and faculty rated the tele-ultrasound course highly (4.6-5.0 on a 5-point scale) for effectiveness of virtual lectures, tele-ultrasound hands-on scanning sessions, and course administration. Faculty generally expressed less satisfaction with their ability to engage with learners, troubleshoot image acquisition, and provide feedback during the tele-ultrasound course but felt learners completed the tele-ultrasound course with a better basic POCUS skillset. CONCLUSIONS: Compared to a traditional in-person course, tele-ultrasound POCUS CME courses appeared to be as effective for improving POCUS knowledge post-course and fulfilling learning objectives. Our findings can serve as a roadmap for educators seeking guidance on development of a tele-ultrasound POCUS training course whose demand will likely persist beyond the COVID-19 pandemic.