Isasi, Carmen R.

ImportanceIdentifying factors associated with resilience during the COVID-19 pandemic can inform targeted interventions and resource allocation for groups disproportionately affected by systemic inequities.ObjectiveTo examine factors associated with self-reported resilience during the COVID-19 pandemic in racially and ethnically diverse, community-dwelling US adults.Design, Setting, and ParticipantsThis cross-sectional study was conducted as part of the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study, which assessed the associations of the pandemic with self-reported resilience of participants from 14 established US prospective cohorts since January 2021. This report includes participants who responded to the self-reported resilience question on C4R questionnaires. Data was initially analyzed from October 2023 to May 2024, with updated analyses performed from August 2024 to April 2025.ExposureRace and ethnicity, behavior factors, health conditions, and social determinants of health measurements accessed before and during the COVID-19 pandemic through cohort visits and C4R questionnaires.Main Outcomes and MeasuresSelf-reported resilience was collected via 1 question (from the Brief Resilience Scale) in C4R questionnaires, “I tend to bounce back quickly after hard times.” Participants who answered agree or strongly agree were classified as resilient, and those who reported neutral, disagree, or strongly disagree were classified as not resilient. Modified Poisson regression was performed to estimate prevalence ratios (PRs) and access multivariable-adjusted associations with resilience.ResultsOf 31 045 participants (18 672 [60%] women; 10 746 [34.6%] aged <65 years), 1185 (3.8%) identified as American Indian, 6728 (21.7%) as Black, 293 (0.9%) as East Asian, 6311 (20.3%) as Hispanic, 565 (1.8%) as South Asian, and 15 961 (51.3%) as White; a total of 23 103 participants (74.4%) self-identified as resilient. Compared with White participants, Black and Hispanic participants had higher prevalence of self-reported resilience (adjusted PR [aPR], 1.04; 95% CI, 1.02-1.06; aPR, 1.08; 95% CI, 1.06-1.11; respectively) and American Indian and East Asian participants had lower prevalence (aPR, 0.90; 95% CI, 0.86-0.94; aPR, 0.76; 95% CI, 0.68-0.84; respectively). Higher education, being married or living as married, higher income, and overweight were also associated with higher prevalence of resilience. Being female, having diabetes, and being unemployed were associated with lower prevalence of self-reported resilience. Compared with participants with public insurance only, participants with private insurance had higher prevalence of resilience (aPR, 1.07; 95% CI, 1.03-1.10). COVID-19 vaccination and infection statuses were not significantly associated with resilience. Modification analyses showed important racial and ethnic differences in how factors such as hypertension, marital status, and insurance status were associated with resilience.Conclusions and RelevanceIn this cross-sectional study of 31 045 adults, self-reported resilience varied by race, ethnicity, and sociodemographic factors. These findings highlight the complex interplay of individual and social factors in shaping the perception of resilience.

Abstract RATIONALE: Chronic lower respiratory diseases (CLRD) confer higher risks from respiratory viral infections, hence CLRD patients are prioritized for influenza, pneumococcal, and COVID-19 vaccination. Nonetheless, vaccine deferral and declination remain common. Given that COVID-19 vaccination is particularly polarizing, and attitudes toward it may differ from other vaccines, we assessed COVID-19 vaccination behaviors and attitudes in adults with versus without CLRD and/or smoking history, which is strongly associated with CLRD risk. METHODS: We pooled data from 10 cohorts participating in the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) that collected pre-pandemic data on self-reported physician diagnosis of asthma or COPD. C4R assessed COVID-19 vaccination status through three waves of standardized questionnaires (2020-2022, 2021-2023, 2023-2024). Prompt COVID-19 vaccination was defined as self-report of receiving at least one COVID-19 vaccine by May 1, 2021. Cumulative COVID-19 vaccine count was self-reported on the Wave 3 Questionnaire. Vaccine attitudes and receipt of influenza and/or pneumococcal vaccines were self-reported on the Wave 1 or 2 Questionnaire. Age-adjusted Poisson regression was used to test associations of vaccination behaviors with CLRD and smoking status at the most recent pre-pandemic exam. RESULTS: Of 20,034 participants (pre-pandemic COPD, 9.3%; asthma, 11.7%; current smoking, 13.4%; former smoking, 36.3%), 64.2% reported prompt COVID-19 vaccination. Among the subset of 10,626 participants completing the Wave 3 Questionnaire in 2023-24, the median COVID-19 vaccine count was 3 (Q1:2, Q3:4). Compared to participants without CLRD, prompt vaccination was more likely in those with asthma (RR=1.04, 95%CI:1.01-1.07, p=0.008) and less likely with COPD (RR=0.94, 95%CI:0.91-0.98, p=0.001), but there were no differences in doses for asthma and COPD. Compared to never smokers, former smoking participants were more likely to receive prompt vaccination (RR=1.11, 95%CI:1.08-1.13, p<0.0001) and more vaccine doses (RR=1.03, 95%CI:1.01-1.05, p=0.015); conversely, current smoking was inversely associated with prompt vaccination (RR=0.94, 95%CI:0.91-0.97, p=0.001) and was associated with fewer doses (RR=0.93, 95%CI:0.89-0.96, p<0.0001). Participants with CLRD versus without CLRD were more likely to report receiving influenza and pneumococcal vaccines, but they were more likely to believe that vaccines are unsafe or ineffective (figure). CONCLUSIONS: COPD was associated with lower likelihood of prompt COVID-19 vaccination. Current smoking was associated with both lower likelihood of prompt COVID-19 vaccination and a lower number of COVID-19 vaccine doses by 2023-24. These associations may be partly attributed to negative vaccine attitudes and beliefs. How the COVID-19 pandemic may have influenced vaccine behaviors and attitudes merits additional study.

Abstract RATIONALE: Deferral and declination of the COVID-19 vaccine is correlated with many factors, including different health guidelines and difficulties accessing the vaccine. In the US, COVID-19 vaccines were made available in tranches of clinical risk starting in December 2020 and were available to all adults on April 19, 2021. In the post-pandemic period, repeating COVID-19 vaccination with updated formulations is broadly recommended. Given that the public health impact of vaccine allocation strategies depends on public acceptance of vaccination, we aimed to evaluate demographic, clinical and social correlates of (1) receiving at least one COVID-19 vaccine by May 1, 2021 (prompt vaccination) and (2) the total number of vaccine doses received (vaccine count) through 2023-2024. METHODS: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a prospective observational meta-cohort study comprising 14 extant NIH-funded population-based cohorts. C4R assessed COVID-19 vaccination using three waves of standardized questionnaires (2020-2021, 2021-2023, 2023-2024). Prompt vaccination was defined by participant self-report of vaccination before May 1, 2021; participants vaccinated after May1, 2021 were classified as non-prompt; participants with missing vaccination information were excluded. Vaccine count was defined by self-report on the 2023-2024 wave Questionnaire. Demographic, clinical and social factors were classified by self-report and/or objective measures from the most recent pre-pandemic cohort exam. Poisson models regressed either prompt vaccination or vaccine count on pre-pandemic factors. RESULTS: Of 17,866 participants (mean age, 6713 years; 60.1% female; 42.1% non-Hispanic White, 22.0% Black, 28.9% Hispanic/Latino, 3.4% American Indian, 2.3% South Asian, 1.4% East Asian), 11,481 (64.3%) reported prompt vaccination. Of the subset of 14,529 participants completing the Wave 3 questionnaire, the median vaccine count in 2023-24 was 3 (Q1, 2; Q3 4). Likelihood of prompt vaccination was higher with greater age, income, and education and with history of diabetes and hypertension; prompt vaccination was less likely with male sex, current smoking, and non-White race and ethnicity (table). Similar associations were observed with respect to vaccine count (table). CONCLUSIONS: In a diverse C4R cohort community-based sample, earlier and greater COVID-19 vaccination was associated with older age and several clinical comorbidities; in contrast, later and lesser vaccine uptake was observed among historically marginalized groups. Whether disparities in COVID-19 vaccination could contribute to disparities in post-COVID-19 conditions merits further investigation.

Abstract Rationale: SARS-CoV-2 infection may be associated with new or worsening respiratory symptoms that, if persistent, may contribute to “Long COVID.” Research is needed on the prevalence and risk determinants of Long COVID and related respiratory symptoms in adults with and without pre-existing obstructive lung disease or smoking history. Methods: C4R is a prospective, observational study that collected information on SARS-CoV-2 infection using standardized methods across 14 NIH-funded cohorts. The third wave of C4R questionnaires, administered June 2023 to January 2025, assessed self-reported Long COVID via the question, “Do you think that you are experiencing, or have ever experienced, what has been called “long COVID,” or symptoms related to COVID at least a month after your infection?” Questionnaires also assessed the presence (vs absence) of 22 symptoms that have been linked to Long COVID, including cough, shortness of breath, and post-exertional malaise. Pre-pandemic obstructive lung disease (COPD or asthma) and smoking status (ever/never) were harmonized from self-reported data collected at the most recent pre-pandemic cohort exam. Poisson regression was used to assess prevalence ratios (PRs) adjusting for age, sex, BMI, education, and pre-pandemic hypertension, diabetes, cardiovascular disease, and depressive symptoms. PRs for respiratory symptoms were tested according to self-reported Long COVID and history of non-hospitalized or hospitalized infection; effect modification by pre-pandemic lung disease and smoking was assessed by multiplicative interaction terms and in fully stratified models. Results: Among 23,434 questionnaire respondents, 1,484 (6.3%) self-reported Long COVID, including 246/1,262 (19.5%) with pre-pandemic lung disease and 664/4,018 (16.5%) with smoking history. The adjusted PR for Long COVID was 1.17 (95%CI:0.99-1.39;P=0.06) comparing participants with/without lung disease and 1.17 (95%CI:1.04-1.32;P=0.01) comparing participants with/without smoking history. Respiratory symptoms were more prevalent in those with self-reported Long COVID, as well as in those with a history of hospitalized or non-hospitalized infection (Table). Associations were generally stronger in participants without pre-pandemic lung disease (p-interaction<0.05 for all comparisons). Respiratory symptoms were also more prevalent with a history of repeated, and pre-Omicron infections, and were less prevalent among participants vaccinated prior to their first infection; findings were similar even after excluding participants with self-reported Long COVID. Conclusions: Long COVID is common, particularly in adults with pre-existing COPD or asthma or smoking history. Long COVID and history of SARS-CoV-2 infection, including non-hospitalized infections, was associated with greater respiratory symptom burden. Whether SARS-CoV-2 infection or Long COVID are associated with development or progression of obstructive lung diseases warrants future studies.

Background: Despite the availability of effective vaccines and a recent decrease in annual deaths, coronavirus disease-2019 (COVID-19) remains a leading cause of death. Serological studies of anti-nucleocapsid (N) antibody response to infection provide insights into host immunobiology of adaptive immune response, which holds promise for identifying high-risk individuals for adverse acute and chronic COVID-19 outcomes. Hypothesis: Among participants previously infected with SARS-CoV-2, traditional vascular disease risk factors are associated with higher anti-N antibodies while vaccination is associated with lower anti-N antibodies. Methods: Among previously infected participants, anti-N antibodies were measured from dried blood spots collected between February 2021-February 2023 among 1,419 Collaborative Cohort of Cohorts for COVID-19 Research (C4R) participants with prior SARS-CoV-2 infection. We measured anti-N IgG antibodies reported as median fluorescence intensity (MFI) units; reactivity (i.e., seropositivity) was defined based on MFI above a validated threshold. Vascular disease risk factors were assessed via pre-pandemic in-person examination, questionnaires, and medical record review. Multivariable generalized linear models regressed anti-N reactivity (modified Poisson) or LN transformed MFI (linear). Results: Among 1,419 participants with prior infection, mean age (standard deviation) was 65.8(12.1) years, 61% were women, and 42.8% were self-reported from a race/ethnicity minority group. Participant reactivity to nucleocapsid peaked at 69% by 4 months post-infection and waned to only 44% ≥12 months after infection. After multivariable adjustment, higher anti-N antibody response was associated with older age, Hispanic (vs. White) or American Indian (vs. White) race/ethnicity, lower income and education, former smoking, and higher anti-spike antibody levels. Asian race (vs. White) and vaccination ( even after infection ) were associated with lower nucleocapsid reactivity; common cardiometabolic co-morbidities were not associated with anti-N reactivity or levels (Figures 1 and 2). Conclusions: Among participants previously infected with SARS-CoV-2, select sociodemographic and behavioral risk factors were associated with higher anti-N antibody levels while vaccination was associated with lower anti-N antibody levels. The observation that vaccination, even after infection, is related to lower anti-N antibody levels merits further investigation.

Abstract Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health–funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.

Background: High adherence to the Mediterranean Diet (MeDi) was associated with better cognitive performance and decreased memory decline among Hispanic or Latino adults. Objective: Investigate if higher adherence to the MeDi improves white matter (WM) integrity among Hispanic/Latino adults and if this effect is mediated by cardiovascular health (CVH). Methods: We included 2,774 participants from the Study of Latinos-Investigation of Neurocognitive Aging-MRI Ancillary Study. Participants completed 24-hour dietary recalls at baseline (2008-2011) which were used to calculate a MeDi score (MeDiS, range 0-9). Brain MRI and diffusion tensor images were collected between 2018 and 2022 on a 3T MRI scanner using a standardized protocol. WM integrity was ascertained using WM hyperintensity (WMH) volume and fractional anisotropy (FA). WMH volumes were residualized for total cranial volume and Ln-transformed prior to analysis. The association of MRI outcomes with MeDiS and its components was investigated using weighted linear regression analysis with complex survey design adjusting for age, sex, sociodemographic characteristics. Cardiovascular health was assessed using the Life’s Simple 7 (LS7, range 0-14) score. The mediating effect of LS7 on the primary outcome was reported as Average Causal Mediation Effects (ACME) and Average Direct Effects (ADE). Statistical significance was set at p<0.05. Results: Mean age (95% CI) at MRI scan was 64.0 (63.4 to 65.2) and 44% were males. Mean MeDiS was 5.01 (4.89 to 5.12) and LS7 was 7.1 (7.0 to 7.3). In our fully adjusted model, increasing MeDi adherence was associated with decreased LnWMH volume (β=-0.07, 95% CI -0.10 to -0.03) and increased FA (β=0.002, 95% CI 0.001 to 0.003). Increasing LS7 scores partially mediated the relationship between MeDiS and WMHs (ACME=-0.01, ADE=-0.08, p<0.05, percent mediation=9%) and between MeDiS and FA (ACME=0.0001, ADE=0.002, p<0.01, percent mediated=8%). Among the different MeDi components, consumption of whole grains and fish above sex-specific energy adjusted energy median intake predicted lower WMH volume and increase FA (p<0.05 for both). Conclusions: Among diverse Hispanic/Latino adults, high MeDi adherence was associated with preserved WM integrity. This association was partially mediated by CVH. This suggests that the beneficial effect of MeDi on brain health is not fully explained by vascular risk factors. A culturally tailored MeDi may preserve brain health among Hispanic/Latino adults.

ImportancePersistent symptoms and disability following SARS-CoV-2 infection, known as post–COVID-19 condition or “long COVID,” are frequently reported and pose a substantial personal and societal burden.ObjectiveTo determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.Design, Setting, and ParticipantsFor this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health–funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection.ExposurePreinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires.Main Outcomes and MeasuresProbability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days.ResultsOf 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P &amp;lt; .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections.Conclusions and RelevanceIn this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.