Seroincidence of SARS-CoV-2 infection prior to and during the rollout of vaccines in a community-based prospective cohort of U.S. adults (preprint)

Background Infectious disease surveillance systems, which largely rely on diagnosed cases, underestimate the true incidence of SARS-CoV-2 infection, due to under-ascertainment and underreporting. We used repeat serologic testing to measure N-protein seroconversion in a well-characterized cohort of U.S. adults with no serologic evidence of SARS-CoV-2 infection to estimate the incidence of SARS-CoV-2 infection and characterize risk factors, with comparisons before and after the start of the SARS-CoV-2 vaccine and variant eras. Methods We assessed the incidence rate of infection and risk factors in two sub-groups (cohorts) that were SARS-CoV-2 N-protein seronegative at the start of each follow-up period: 1) the pre-vaccine/wild-type era cohort (n=3,421), followed from April to November 2020; and 2) the vaccine/variant era cohort (n=2,735), followed from November 2020 to June 2022. Both cohorts underwent repeat serologic testing with an assay for antibodies to the SARS-CoV-2 N protein (Bio-Rad Platelia SARS-CoV-2 total Ab). We estimated crude incidence and sociodemographic/epidemiologic risk factors in both cohorts. We used multivariate Poisson models to compare the risk of SARS-CoV-2 infection in the pre-vaccine/wild-type era cohort (referent group) to that in the vaccine/variant era cohort, within strata of vaccination status and epidemiologic risk factors (essential worker status, child in the household, case in the household, social distancing). Findings In the pre-vaccine/wild-type era cohort, only 18 of the 3,421 participants (0.53%) had >1 vaccine dose by the end of follow-up, compared with 2,497/2,735 (91.3%) in the vaccine/variant era cohort. We observed 323 and 815 seroconversions in the pre-vaccine/wild-type era and the vaccine/variant era and cohorts, respectively, with corresponding incidence rates of 9.6 (95% CI: 8.3-11.5) and 25.7 (95% CI: 24.2-27.3) per 100 person-years. Associations of sociodemographic and epidemiologic risk factors with SARS-CoV-2 incidence were largely similar in the pre-vaccine/wild-type and vaccine/variant era cohorts. However, some new epidemiologic risk factors emerged in the vaccine/variant era cohort, including having a child in the household, and never wearing a mask while using public transit. Adjusted incidence rate ratios (aIRR), with the entire pre-vaccine/wild-type era cohort as the referent group, showed markedly higher incidence in the vaccine/variant era cohort, but with more vaccine doses associated with lower incidence: aIRRun/undervaccinated=5.3 (95% CI: 4.2-6.7); aIRRprimary series only=5.1 (95% CI: 4.2-7.3); aIRRboosted once=2.5 (95% CI: 2.1-3.0), and aIRRboosted twice=1.65 (95% CI: 1.3-2.1). These associations were essentially unchanged in risk factor-stratified models. Interpretation In SARS-CoV-2 N protein seronegative individuals, large increases in incidence and newly emerging epidemiologic risk factors in the vaccine/variant era likely resulted from multiple co-occurring factors, including policy changes, behavior changes, surges in transmission, and changes in SARS-CoV-2 variant properties. While SARS-CoV-2 incidence increased markedly in most groups in the vaccine/variant era, being up to date on vaccines and the use of non-pharmaceutical interventions (NPIs), such as masking and social distancing, remained reliable strategies to mitigate the risk of SARS-CoV-2 infection, even through major surges due to immune evasive variants. Repeat serologic testing in cohort studies is a useful and complementary strategy to characterize SARS-CoV-2 incidence and risk factors.

Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium (preprint)

Introduction Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes. Methods The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA’s 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys. Results The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi’s sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate. Conclusion IeDEA’s approach for site survey development approach has broad relevance for HIV research networks and other priority health conditions.

Racial/ethnic disparities in exposure to COVID-19, susceptibility to COVID-19 and access to health care - findings from a U.S. national cohort (preprint)

We examined the influence of racial/ethnic differences in socioeconomic position on COVID-19 seroconversion and hospitalization within a community-based prospective cohort enrolled in March 2020 and followed through October 2021 (N=6740). The ability to social distance as a measure of exposure to COVID-19, susceptibility to COVID-19 complications, and access to healthcare varied by race/ethnicity with non-white participants having more exposure risk and more difficulty with healthcare access than white participants. Participants with more (versus less) exposure had greater odds of seroconversion (aOR:1.64, 95% Confidence Interval [CI] 1.18-2.29). Participants with more susceptibility and more barriers to healthcare had greater odds of hospitalization (respective aOR:2.36; 1.90-2.96 and 2.31; 1.69-2.68). Race/ethnicity positively modified the association between susceptibility and hospitalization (aORnon-White:2.79, 2.06-3.78). Findings may explain the disproportionate burden of COVID-19 infections and complications among Hispanic and non-Hispanic Black persons. Primary and secondary prevention efforts should address disparities in exposure, COVID-19 vaccination, and treatment.

Risk Profile of Thanksgiving Gatherers and Subsequent SARS-CoV2 Testing and Diagnosis (preprint)

ABSTRACT Background During Fall 2020 in the United States (U.S.), despite high COVID-19 case numbers and recommendations from public health officials not to travel and gather with individuals outside one’s household, millions of people gathered for Thanksgiving. The objective of this study was to understand if individuals’ behaviors and risk perceptions influenced their decision to gather, and if they did gather, their subsequent test seeking and diagnoses. Methods Participants were part of the CHASING COVID Cohort study - a U.S. national prospective cohort. The study sample consisted of participants who completed routine questionnaires before and after Thanksgiving. Non-pharmaceutical interventions (NPIs) use informed behavioral risk scores and a score of perceived risk of COVID-19 were assigned to each participant. Multinomial logistic regression models were used to assess the association between higher risk behaviors and gathering with other households, and the association of gathering with subsequent testing and test positivity. Results A total of 1,932 (40.5%) cohort participants spent Thanksgiving with individuals from at least one other household. Participants with higher behavioral risk scores had greater odds of gathering with one other household (aOR: 2.35, 95% CI: 2.0, 2.7), two other households (aOR: 4.54, 95% CI: 3.7, 5.6), and three or more other households (aOR: 5.44, 95% CI: 4.1, 7.2). Participants perceiving COVID-19 as a low-risk to themselves and others had greater odds of gathering with one other household (aOR: 1.12, 95% CI: 0.97, 1.3), two other households (aOR: 1.39, 95% CI: 1.1, 1.7), and three or more other households (aOR: 1.86, 95% CI: 1.4, 2.4). Those who spent Thanksgiving with one or more other households had 1.23 times greater odds (95% CI: 1.1, 1.4) of having a COVID-19 test afterward. There was no association between gathering for Thanksgiving and subsequent COVID-19 test positivity or developing COVID-19 symptoms. Conclusions Those who gathered with other households for Thanksgiving tended to engage in higher-risk activities. Thanksgiving gathering with other households was not associated with subsequently testing positive for COVID-19, but only a small proportion obtained post-travel testing. Public health messaging should emphasize behavior change strategies that promote safer gathering.

Spread and sources of information and misinformation about COVID-19 early during the pandemic in a U.S. national cohort study (preprint)

Background: Early in the pandemic, misinformation about COVID-19 was spread on social media. The purpose of this study was to describe trusted sources of COVID-19 information and claims seen and believed about COVID-19 early in the pandemic among U.S. adults. Then, we assessed the impact of believing such claims on engaging in personal protective actions (PPA). Methods: We used baseline data from the CHASING COVID Cohort (n = 7,070) collected March 28, 2020 to April 20, 2020 to describe trusted sources of COVID-19 information as well as claims circulating on social media that had been seen and believed. We used Poisson regression to determine the association of believing certain claims with engaging in a higher number of PPA. Results: The top three trusted sources of COVID-19 information were the CDC (67.9%), the WHO (53.7%), and State Health Departments (53.0%). Several COVID-19 claims circulated on social media had been seen, e.g., that the virus was created in a laboratory (54.8%). Moreover, substantial proportions of participants indicated agreement with some of these claims. In multivariable regression, we found that belief in certain claims was associated with engaging in a higher number of PPA. For example, believing that paper masks would prevent transmission of the virus was associated with engaging in a higher number of protective actions ({beta} = 0.02, 95% CI: 0.004 - 0.046). Conclusions: Results suggest the need for public health leadership on social media platforms to combat misinformation and supports social media as a tool to further public health interventions.

Recent SARS-CoV-2 seroconversion in a national, community-based prospective cohort of U.S. adults (preprint)

SHORT ABSTRACTEpidemiologic risk factors for incident SARS-CoV-2 infection are best characterized via prospective cohort studies, complementing case-based surveillance and cross-sectional seroprevalence studies. In March 2020, we launched the CHASING COVID Cohort Study, a national, community-based prospective cohort study of 6,745 U.S. adults who underwent at-home specimen collection for repeat serologic testing for SARS-CoV-2 antibodies. We identify and quantify several policy-sensitive risk factors for recent SARS-CoV-2 seroconversion, highlight persistent racial/ethnic disparities in incidence, document continued elevated risk among essential workers, and call attention to major gaps in the coverage of public health interventions aimed at testing, isolation, and contact tracing. We conclude that modifiable risk factors and poor reach of public health strategies drive SARS-CoV-2 transmission and inequities across the U.S.

Household factors and the risk of severe COVID-like illness early in the US pandemic (preprint)

ObjectiveTo investigate the role of children in the home and household crowding as risk factors for severe COVID-19 disease. MethodsWe used interview data from 6,831 U.S. adults screened for the Communities, Households and SARS/CoV-2 Epidemiology (CHASING) COVID Cohort Study in April 2020. ResultsIn logistic regression models, the adjusted odds ratio [aOR] of hospitalization due to COVID-19 for having (versus not having) children in the home was 10.5 (95% CI:5.7-19.1) among study participants living in multi-unit dwellings and 2.2 (95% CI:1.2-6.5) among those living in single unit dwellings. Among participants living in multi-unit dwellings, the aOR for COVID-19 hospitalization among participants with more than 4 persons in their household (versus 1 person) was 2.5 (95% CI:1.0-6.1), and 0.8 (95% CI:0.15-4.1) among those living in single unit dwellings. ConclusionEarly in the US SARS-CoV-2 pandemic, certain household exposures likely increased the risk of both SARS-CoV-2 acquisition and the risk of severe COVID-19 disease.

The relationship between anxiety, health, and potential stressors among adults in the United States during the COVID-19 pandemic (preprint)

Objective: To estimate the prevalence of anxiety symptoms and the association between moderate or severe anxiety symptoms and health and potential stressors among adults in the U.S. during the COVID-19 pandemic Methods: This analysis includes data from 5,250 adults in the Communities, Households and SARS/CoV-2 Epidemiology (CHASING) COVID Cohort Study surveyed in April 2020. Poisson models were used to estimate the association between moderate or severe anxiety symptoms and health and potential stressors among U.S. adults during the COVID-19 pandemic. Results: Greater than one-third (35%) of participants reported moderate or severe anxiety symptoms. Having lost income due to COVID-19 (adjusted prevalence ratio [aPR] 1.27 (95% CI 1.16, 1.30), having recent COVID-like symptoms (aPR 1.17 (95% CI 1.05, 1,31), and having been previously diagnosed with depression (aPR 1.49, (95% CI 1.35, 1.64) were positively associated with anxiety symptoms. Conclusions: Anxiety symptoms were common among adults in the U.S. during the COVID-19 pandemic. Strategies to screen and treat individuals at increased risk of anxiety, such as individuals experiencing financial hardship and individuals with prior diagnoses of depression, should be developed and implemented.

Testing, Testing: What SARS-CoV-2 testing services do adults in the United States actually want? (preprint)

Importance: Ascertaining preferences for SARS-CoV-2 testing and incorporating findings into the design and implementation of strategies for delivering testing services may enhance testing uptake and engagement, a prerequisite to reducing onward transmission. Objective: To determine important drivers of decisions to obtain a SARS-CoV-2 test in the context of increasing community transmission. Design: A discrete choice experiment (DCE) was used to assess the relative importance of type of SARS-CoV-2 test, specimen type, testing venue, and results turnaround time. Uptake of an optimized testing scenario was simulated relative to the current typical testing scenario of polymerase chain reaction (PCR) via nasopharyngeal (NP) swab in a provider office or urgent care clinic with results in >5 days. Setting: Online survey, embedded in an existing cohort study, conducted during July 30 - September 8, 2020. Participants: Participants (n=4,793) were enrolled in the CHASING COVID Cohort Study, a national longitudinal cohort of adults >18 years residing in the 50 US states, Washington, DC, Puerto Rico, or Guam. Main Outcome(s) and Measure(s): Relative importance of SARS-CoV-2 testing method attributes, utilities of specific attribute levels, and probability of choosing a testing scenario based on preferences estimated from the DCE, the current typical testing option, or choosing not to test. Results: Turnaround time for test results had the highest relative importance (30.4%), followed by test type (28.3%), specimen type (26.2%), and venue (15.0%). Participants preferred fast results on both past and current infection and using a noninvasive specimen, preferably collected at home. Simulations suggested that providing immediate or same day test results, providing both PCR and serology, or collecting oral specimens would substantially increase testing uptake over the current typical testing option. Simulated uptake of a hypothetical testing scenario of PCR and serology via a saliva sample at a pharmacy with same day results was 97.7%, compared to 0.6% for the current typical testing scenario, with 1.8% opting for no test. Conclusions and Relevance: Testing strategies that offer both PCR and serology with non-invasive methods and rapid turnaround time would likely have the most uptake and engagement among residents in communities with increasing community transmission of SARS-CoV-2.

A national prospective cohort study of SARS/COV2 pandemic outcomes in the U.S.: The CHASING COVID Cohort (preprint)

Introduction: The Chasing COVID Cohort (C3) study is a US-based, geographically and socio-demographically diverse sample of adults (18 and older) enrolled into a prospective cohort study during the upswing of the U.S. COVID-19 pandemic. Methods: We used internet-based strategies to enroll C3 participants beginning March 28th, 2020. Following baseline questionnaire completion, study participants will be contacted monthly (for 6 months) to complete assessments of engagement in non-pharmaceutical interventions (e.g., use of cloth masks, avoiding large gatherings); COVID-19 symptoms; SARS/COV2 testing and diagnosis; hospitalizations; healthcare access; and uptake of health messaging. Dried blood spot (DBS) specimens will be collected at the first follow-up assessment (last week of April 2020) and at month 3 (last week of June 2020) and stored until a validated serologic test is available. Results: As of April 20, 2020, the number of people that completed the baseline survey and provided contact information for follow-up was 7,070. Participants resided in all 50 US states, the District of Columbia, Puerto Rico, and Guam. At least 24% of participants were frontline workers (healthcare and other essential workers). Twenty-three percent (23%) were 60+ years, 24% were Black or Hispanic, 52% were men, and 52% were currently employed. Nearly 20% reported recent COVID-like symptoms (cough, fever or shortness of breath) and a high proportion reported engaging in non-pharmaceutical interventions that reduce SARS/COV2 spread (93% avoided groups >20, 58% wore masks; 73% quarantined). More than half (54%) had higher risk for severe COVID-19 illness should they become infected with SARS/COV2 based on age, underlying health conditions (e.g., chronic lung disease), or daily smoking. Discussion: A geographically and socio-demographically diverse group of participants was rapidly enrolled in the C3 during the upswing of the SARS/COV2 pandemic. Strengths of the C3 include the potential for direct observation of, and risk factors for, seroconversion and incident COVID disease (among those with or without antibodies to SARS/COV2) in areas of active transmission.