Incidence of Respiratory Syncytial Virus Infection in Older Adults Before and During the COVID-19 Pandemic.

Importance: Little is known about the burden and outcomes of respiratory syncytial virus (RSV)-positive acute respiratory infection (ARI) in community-dwelling older adults. Objective: To assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults. Design, Setting, and Participants: This was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI. Exposure: RSV-positive and -negative ARI. Main Outcomes and Measures: RSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed. Results: In this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, -16.7 [95% CI, -31.8 to -1.8]; fatigue, -8.4 [95% CI, -14.3 to -2.4]; and difficulty in social functioning, -11.9 [95% CI, -19.8 to -4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: -4.0 [95% CI, -8.5 to -1.3]; difficulty in social functioning, -5.8 [95% CI, -10.3 to -1.3]; and limitation due to emotional problem, -7.0 [95% CI, -12.7 to -1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, -4.4 [95% CI, -7.3 to -1.5]; difficulty in social functioning, -5.2 [95% CI, -8.7 to -1.7] and limitation due to emotional problem, -5.7 [95% CI, -10.7 to -0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities. Conclusions and Relevance: In this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.

Adherence to Public Health Measures Mitigates the Risk of COVID-19 Infection in Older Adults: A Community-Based Study.

OBJECTIVE: To assess the prevalence and characteristics of coronavirus disease 2019 (COVID-19) cases during the reopening period in older adults, given that little is known about the prevalence of COVID-19 after the stay-at-home order was lifted in the United States, nor the actual effects of adherence to recommended public health measures (RPHM) on the risk of COVID-19. PATIENTS AND METHODS: This was a cross-sectional study nested in a parent prospective cohort study, which followed a population-based sample of 2325 adults 50 years and older residing in southeast Minnesota to assess the incidence of viral infections. Participants were instructed to self-collect both nasal and oropharyngeal swabs, which were tested by reverse transcription polymerase chain reaction-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay between May 8, 2020, and June, 30, 2020. We assessed the prevalence of COVID-19 cases and characteristics of study subjects. RESULTS: A total of 1505 eligible subjects participated in the study whose mean age was 68 years, with 885 (59%) women, 32 (2%) racial/ethnic minorities, and 906 (60%) with high-risk conditions for influenza. The prevalence of other Coronaviridae (human coronavirus [HCoV]-229E, HCoV-NL63, and HCoV-OC43) during the 2019 to 2020 flu season was 109 (7%), and none tested positive for SARS-CoV-2. Almost all participants reported adhering to the RPHM (1,488 [99%] for social distancing, 1,438 [96%] for wearing mask in a public space, 1,476 [98%] for hand hygiene, and 1,441 (96%) for staying home mostly). Eighty-six percent of participants resided in a single-family home. CONCLUSION: We did not identify SARS-COV-2 infection in our study cohort. The combination of participants' behavior in following the RPHM and their living environment may considerably mitigate the risk of COVID-19.