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BACKGROUND COVID-19 has disproportionately affected older adults. Frailty has been associated with impaired vaccine response in other vaccine types, but the impact of frailty on mRNA vaccine response is undefined. METHODS Observational study of adults aged 55 and above from one US health care system between January 22, 2021 and September 16, 2021 with self-reported Moderna or Pfizer COVID-19 mRNA vaccine and an electronic frailty index score (eFI) from their medical record (n =1677). Participants’ frailty status was compared with positive antibody detection (seroconversion) following full vaccination and subsequent loss of positive antibody detection (seroreversion) using logistic regression models. RESULTS Of 1677 older adults with median (IQR) age, 67 (62, 72) years, and frailty status (non-frail: 879 (52%), pre-frail: 678 (40%), and frail: 120 (7.2%)), seroconversion was not detected in 23 (1.4%) over 60 days following full vaccination. Frail individuals were less likely to seroconvert than non-frail individuals, adjusted OR 3.75, 95%CI (1.04, 13.5). Seroreversion was detected in 50/1631 individuals (3.1%) over 6 months of median follow up antibody testing. Frail individuals were more likely to serorevert than non-frail individuals, adjusted OR 3.02, 95%CI (1.17, 7.33). CONCLUSIONS Overall antibody response to COVID-19 mRNA vaccination was high across age and frailty categories. While antibody detection is an incomplete descriptor of vaccine response, the high sensitivity of this antibody combined with health system data reinforce our conclusions that frailty is an independent predictor of impaired antibody response to the COVID-19 mRNA vaccines. Frailty should be considered in vaccine studies and prevention strategies.

Background Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. Methods We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables. Results Participants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p < 0.001), which was further impaired with higher frailty (p = 0.001). Notably, avidity increased to peak levels after the booster (p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells (p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty (p = 0.056, adjusted for COVID-19). Conclusions We evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.

T he evolution of SARS-CoV-2 during the CO-VID-19 pandemic has raised interest in evolving disease manifestation and associated severity since early reports of its emergence in December 2019 (1). As SARS-CoV-2 variants have evolved, studies have focused on the differences in hospitalizations and deaths (2,3). Although case reports have described changes in symptoms, they are limited in scope and duration of follow-up (4-8). Moreover, because these retrospective case investigations are often event based, separating novel symptoms from preinfection symptoms is subject to recency bias (9), and does not establish a true distribution of these symptoms, unlike prospective syndromic surveillance. The purpose of this study was to describe the evolution of COVID-19 symptoms and their duration during each variant wave in the North Carolina COVID-19 Community Research Partnership (NC-CCRP), a multisite longitudinal symptom and serosurveillance study in North Carolina, USA, that included results from an electronic daily symptom survey regardless of infection status. The StudyThe NC-CCRP is one of the largest and longest running syndromic surveillance surveys of a convenience cohort in the United States. In the study, a total of 37,820 adult participants completed daily health and symptom logs during April 2020-April 2022 and captured 5,480 self-reported COVID-19 infections (10). Adults >18 years of age were recruited from the patient populations served by healthcare systems at 6 North Carolina sites via direct email outreach. Participants received a brief daily electronic survey by text or email to answer questions about COVID-19 exposures, symptoms, test results, receipt of vaccination, and risk behaviors. We obtained demographic information and healthcare worker occupation at baseline. Participants provided informed consent electronically. We defined variant periods as pre-Delta, Delta, and Omicron (pre-BA.4/BA.5) based on variant predominance in North Carolina (Figure 1). We defined symptomatic COVID-19 as the presence of >1 new symptom 2 weeks before or after the date of a self-reported positive viral test. A new symptom occurred if the symptom was not present in the 7 days before the report date. We defined reinfection as a positive test result >90 days after a previous positive test.

Monkeypox testing delays: The need for drastic expansion of education and testing for monkeypox virus.