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Background: Adults with cardiovascular co-morbidities and risk factors are at greater risk of severe COVID-19. These same risk factors may also be associated with an attenuated antibody response to COVID-19 vaccines, although studies in diverse, U.S. population-based cohorts have been limited. Methods: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) conducted a serosurvey for SARS-CoV-2 antibodies via dried blood spot (DBS) in 14 U.S. cohorts. IgG antibodies to SARS-CoV-2 spike subunit 1 (S1) and nucleocapsid (N) were measured from DBS using a semi-quantitative microsphere immunoassay and reported as median fluorescence intensity (MFI). Multivariable adjusted linear models regressed log-transformed anti-S1 MFI on age, sex, race/ethnicity, education attainment, self-reported diabetes, hypertension, cardiovascular disease (CVD), chronic kidney disease, smoking history, body mass index (BMI), asthma, obstructive lung diseases, DBS batch, anti-N MFI, vaccine type, time between vaccine and DBS, and vaccine dose at time of DBS collection. Results are presented as the percent difference in anti-S1 MFI compared with a reference group. Results: There were 6614 vaccinated participants prior to booster regimens and DBS collection (April 2021-July 2022) with 50%, 48%, and 2% of the cohort who received BNT162b2, mRNA-1273, or other vaccines, respectively. The mean (SD) time between vaccination and DBS was 3.8 (1.8) months. Over 10% of the cohort had self-reported a history of diabetes, 55% had hypertension, and 74% had a BMI>25 kg/m 2 . Anti-S1 MFI decreased as the time between vaccine dose and DBS collection increased. Diabetes was associated with a 16.1% lower anti-S1 MFI (95%CI:-22.4,-9.5) whereas neither hypertension (-3.8%;95%CI:-9.3,2.1), nor cardiovascular disease history (-5.3%;95%CI:-16.3,7.4) were associated with anti-S1 MFI. Former and current smoking history were each associated with a lower anti-S1 MFI: (-6.6%;95%CI:-12.1,-0.8) and (-16.1%;95%CI:-24.7,-6.6), respectively. Participants with a BMI 25-29.9 kg/m 2 had a 7.6% higher anti-S1 MFI (95%CI:0.3,15.4) whereas those with a BMI of 30-35 kg/m 2 and >35 kg/m 2 had 6.2% (95%CI:-2.4,15.5) higher and 8.9% lower (95%CI:-17.6,0.7) MFI levels, respectively. Older age and male sex were each associated with a lower anti-S1 MFI and mRNA-1273 vaccine, Asian subgroup, higher anti-N titer, and prior COVID-19 infection were each associated with higher anti-S1 MFI. Chronic kidney disease, education attainment, and lung disease were not associated with anti-S1 MFI. Conclusions: Several traditional cardiovascular disease risk factors were associated with diminished humoral responses to the initial COVID-19 vaccine regimens in a diverse U.S. population-based cohort and may have implications on strategies to improve vaccine responses.

Introduction: We and others observed that social distancing enforced early in the COVID-19 pandemic led to an increase in loneliness, a social condition associated with adverse mental and physical health outcomes. Here, we examine longitudinal changes in perceived loneliness over the first two years of the COVD-19 pandemic among older adults participating in the Atherosclerosis Risk in Communities (ARIC) Study. Hypothesis: Perceived loneliness decreased over the course of the pandemic. Methods: The UCLA 3-item Loneliness questionnaire, which assesses lack of companionship, feeling left out, and feeling isolated, to classify level of perceived loneliness, was administered to ARIC participants in March-October 2020 and again in August 2020-March 2022 as part of the Colllaborative Cohort of Cohorts for COVID-19 Research (C4R). Prepandemic measures (Jan-March 2020) were available in a subset. For each item, response categories “hardly ever”, “some of the time” and “often” were scored from 1 to 3, respectively, and added to create a final score ranging from 3 to 9 (higher scores indicating greater loneliness). T-tests were used to compare mean loneliness score values between the measurement periods. Mixed effects linear regression models were fit to examine predictors of change in the loneliness score. Results: Among 2,335 ARIC cohort participants with repeat assessments of loneliness during the COVID-19 pandemic (mean age 82.4 (SD 4.4) years, 64.8% female, 18.5% Black), mean perceived loneliness score decreased from 4.40 (SD 1.51) to 3.78 (SD 1.25) (p-value Conclusion: Despite reporting greater loneliness during the first six months of the COVID-19 pandemic compared to the time prior to the pandemic, older adults reported similar levels of perceived loneliness in the second year of the pandemic compared to pre-pandemic levels. In particular, Black race and and male sex were associated with greater reductions in loneliness over the pandemic period. These results suggest that older adults were psychologically resilient with respect to the extreme social changes associated with the COVID-19 pandemic.

Introduction: E-cigarettes (e-cigs) are the most commonly used tobacco product among youth. While cigarette use has been associated with a history of depression, research on the associations of e-cig use and depressive symptoms remains limited. While other studies have looked at the incidence of depression among e-cig users, the VapeScan study also factors in dual users who both smoke cigarettes and e-cigarettes. Hypothesis: We hypothesized that e-cig use is associated with seeking professional help for depression among young adult participants in the VapeScan Study. Methods: Participants aged 18 to 50 years were recruited from the greater New York area to participate in the VapeScan Study from May 2021 to October 2022. Participants were classified as exclusive current e-cig users (e-cig users), current e-cig and former cigarette users, current e-cig and cigarette users (dual users), or non-users of both e-cigs and cigarettes (controls); former vapers and exclusive cigarette users were excluded from the study. Participants self-reported if they had ever “seen a doctor or other health professional for depression.” Rates of professional care for depression were compared by logistic regression test. Logistic regression was used to test the association between e-cig use status and seeking professional help for depression, adjusted for age, sex, and race/ethnicity. Results: Among 147 participants, mean (SD) age was 28 (8) years, 54.42% (80 of 147) of participants were assigned female at birth, 36.73% (54 of 147) were Non-Hispanic White (ETC). There were 29 e-cig users, 42 dual users, and 76 controls. Forty-one percent of e-cig users (12 of 29) had seen a health professional for depression versus 64% (27 of 42) of dual users and 29% (22 of 76) of controls (p-value=0.0014). After adjustment, compared to controls, e-cig users were 1.66 times more likely to have sought professional care for depression (95%CI: 0.59-4.71) and dual users were 7.90 times more likely (95%CI: 2.99-20.88). Conclusions: E-cig use, and particularly dual use of e-cigs and cigarettes, was associated with having sought professional help for depression among young adults. Persons presenting with depressive symptoms should be screened for tobacco product use, and vice versa, to ensure provision of evidence-based mental health and tobacco cessation programs.

RationaleInflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have anti-inflammatory properties and may benefit lung health.ObjectivesInvestigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in adults of diverse races/ethnicities from general population cohorts.MethodsComplementary study designs: (1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1and FVC measures in the National Heart, Lung, and Blood Institute Pooled Cohorts Study, and (2) two-sample Mendelian Randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters.Measurements and Main ResultsThe longitudinal study found that higher omega-3 fatty acid concentrations were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for docosahexaenoic acid (DHA). One standard deviation higher DHA was associated with an attenuation of 1.8 mL/year for FEV1(95% confidence interval [CI] 1.3–2.2) and 2.4 mL/year for FVC (95% CI 1.9–3.0). One standard deviation higher DHA was also associated with a 9% lower incidence of spirometry-defined airway obstruction (95% CI 0.86–0.97). DHA associations persisted across sexes, smoking histories, and Black, white and Hispanic participants, with the largest magnitude associations in former smokers and Hispanics. The MR study showed positive associations of genetically predicted omega-3 fatty acids with FEV1and FVC, with statistically significant findings across multiple MR methods.ConclusionsThe longitudinal and MR studies provide evidence supporting beneficial effects of higher circulating omega-3 fatty acids, especially DHA, on lung health.

This cohort study examines the association of self-reported postvaccination symptoms with anti–SARS-CoV-2 antibody response among Framingham Heart Study participants contributing to the Collaborative Cohort of Cohorts for COVID-19 Research study.

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) 3He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP 3He MRI measuring pAO2, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm2/s) correlated with emphysema and heterogeneity in pAO2 measurements. Strong correlations were found between the heterogeneity of global pAO2 as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic pAO2 values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between pAO2 SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas pAO2 heterogeneity and the fraction of non-physiological pAO2 results increase in mild to moderate COPD. Measurements of pAO2 are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation.