Secondary Cancer in Prostate Cancer Patients Treated With Advanced External Beam Radiation Therapy.

Purpose: Previous studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and Methods: Using the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: In total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. Conclusion: In this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

Barriers to initial COVID-19 booster among U.S. adults who completed a primary vaccine series in the CHASING COVID cohort, September 2021 - October 2022.

It is crucial to understand factors associated with COVID-19 booster uptake in the U.S. given the updated COVID-19 vaccine recommendations. Using data from a national prospective cohort (N=4,616) between September 2021-October 2022, we examined socioeconomic, demographic, and behavioral factors of initial booster uptake among participants fully-vaccinated with the primary COVID-19 vaccines series. Cox proportional hazards models were used to estimate the associations of each factor with time to initial booster uptake. Most participants (86.5%) reported receiving their initial booster. After adjusting for age, race/ethnicity, education, region, and employment, participants with greater risk for severe COVID-19 had similar booster uptake compared with those with lower risk (aHR: 1.04; 95% CI: 0.95, 1.14). Participants with greater barriers to healthcare (aHR: 0.89; 95% CI: 0.84, 0.96), food insecurity (aHR: 0.82; 95% CI: 0.75, 0.89), and housing instability (aHR: 0.81; 95% CI: 0.73, 0.90) were less likely to report receiving initial booster compared with those without those barriers. Factors motivating the decision to vaccinate changed from safety-related concerns for the primary series to perceived need for the booster. It is key to address economic and health access barriers to achieve equitable COVID-19 vaccine uptake and continued protection against COVID-19.

Perceived Risk for Severe COVID-19 and Oral Antiviral Use Among Antiviral-Eligible US Adults.

INTRODUCTION: Oral antiviral medications are important tools for preventing severe COVID-19 outcomes. However, their uptake remains low for reasons that are not entirely understood. Our study aimed to assess the association between perceived risk for severe COVID-19 outcomes and oral antiviral use among those who were eligible for treatment based on Centers for Disease Control and Prevention (CDC) guidelines. METHODS: We surveyed 4034 non-institutionalized US adults in April 2023, and report findings from 934 antiviral-eligible participants with at least one confirmed SARS-CoV-2 infection since December 1, 2021 and no current long COVID symptoms. Survey weights were used to yield nationally representative estimates. The primary exposure of interest was whether participants perceived themselves to be "at high risk for severe COVID-19." The primary outcome was use of a COVID-19 oral antiviral within 5 days of suspected SARS-CoV-2 infection. RESULTS: Only 18.5% of antiviral-eligible adults considered themselves to be at high risk for severe COVID-19 and 16.8% and 15.9% took oral antivirals at any time or within 5 days of SARS-CoV-2 infection, respectively. In contrast, 79.8% were aware of antiviral treatments for COVID-19. Perceived high-risk status was associated with being more likely to be aware (adjusted prevalence ratio [aPR]: 1.11 [95% confidence interval (CI) 1.03-1.20]), to be prescribed (aPR 1.47 [95% CI 1.08-2.01]), and to take oral antivirals at any time (aPR 1.61 [95% CI 1.16-2.24]) or within 5 days of infection (aPR 1.72 [95% CI 1.23-2.40]). CONCLUSIONS: Despite widespread awareness of the availability of COVID-19 oral antivirals, more than 80% of eligible US adults did not receive them. Our findings suggest that differences between perceived and actual risk for severe COVID-19 (based on current CDC guidelines) may partially explain this low uptake.

Patient Education and Decision Support for Long-Acting Injectable HIV Antiretroviral Therapy: Protocol for Tool Development and Pilot Testing with Ryan White HIV/AIDS Program Medical Case Management Programs in New York.

BACKGROUND: Long-acting injectable (LAI) HIV antiretroviral therapy (ART) presents a major opportunity to facilitate and sustain HIV viral suppression, thus improving health and survival among people living with HIV and reducing the risk of onward transmission. However, realizing the public health potential of LAI ART requires reaching patients who face barriers to daily oral ART adherence and thus can clinically benefit from alternative treatment modalities. Ryan White HIV/AIDS Program Part A medical case management (MCM) programs provide an array of services to address barriers to HIV care and treatment among economically and socially marginalized people living with HIV. These programs have demonstrated effectiveness in improving engagement along the continuum of care, but findings of limited program impact on durable viral suppression highlight the need to further innovate and hone strategies to support long-term ART adherence. OBJECTIVE: This study aims to adapt and expand Ryan White MCM service strategies to integrate LAI ART regimen options, with the larger goal of improving health outcomes in the populations that could most benefit from alternatives to daily oral ART regimens. METHODS: In 3 phases of work involving patient and provider participants, this study uses role-specific focus groups to elicit perceptions of LAI versus daily oral ART; discrete choice experiment (DCE) surveys to quantify preferences for different ART delivery options and related supports; and a nonrandomized trial to assess the implementation and utility of newly developed tools at 6 partnering Ryan White HIV/AIDS Program Part A MCM programs based in urban, suburban, and semirural areas of New York. Findings from the focus groups and DCEs, as well as feedback from advisory board meetings, informed the design and selection of the tools: a patient-facing, 2-page fact sheet, including frequently asked questions and a side-by-side comparison of LAI with daily oral ART; a patient-facing informational video available on YouTube (Google Inc); and a patient-provider decision aid. Implementation outcomes, measured through provider interviews, surveys, and service reporting, will guide further specification of strategies to integrate LAI ART options into MCM program workflows. RESULTS: The study was funded in late April 2021 and received approval from the institutional review board in May 2021 under protocol 20-096. Focus groups were conducted in late 2021 (n=21), DCEs ran from June 2022 to January 2023 (n=378), and tools for piloting were developed by May 2023. The trial (May 2023 through January 2024) has enrolled >200 patients. CONCLUSIONS: This study is designed to provide evidence regarding the acceptability, feasibility, appropriateness, and utility of a package of patient-oriented tools for comparing and deciding between LAI ART and daily oral ART options. Study strengths include formative work to guide tool development, a mixed methods approach, and the testing of tools in real-world safety-net service settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT05833542; https://clinicaltrials.gov/study/NCT05833542. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56892.

Oral COVID-19 Antiviral Uptake Among a Highly Vaccinated US Cohort of Adults With SARS-CoV-2 Infection Between December 2021 and October 2022.

Background: We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022. Methods: We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID). Results: NMV/r uptake was 13.6% (95% CI, 11.9%-15.2%) among 1594 participants, and MOV uptake was 1.4% (95% CI, 0.8%-2.1%) among 1398 participants. NMV/r uptake increased over time (1.9%; 95% CI, 1.0%-2.9%; between 12/2021 and 3/2022; 16.5%; 95% CI, 13.0%-20.0%; between 4/2022 and 7/2022; and 25.3%; 95% CI, 21.6%-29.0%; between 8/2022 and 10/2022). Participants age ≥65 and those who had comorbidities for severe COVID-19 had higher NMV/r uptake. There was lower NMV/r uptake among non-Hispanic Black participants (7.2%; 95% CI, 2.4%-12.0%; relative to other racial/ethnic groups) and among individuals in the lowest income groups (10.6%; 95% CI, 7.3%-13.8%; relative to higher income groups). Among a subset of 278 participants with SARS-CoV-2 infection after 12/2021 who also had a history of prior SARS-CoV-2 infection, those with (vs without) a history of long COVID reported greater NMV/r uptake (22.0% vs 7.9%; P = .001). Among those prescribed NMV/r (n = 216), 137 (63%; 95% CI, 57%-70%) reported that NMV/r was helpful for reducing COVID-19 symptoms. Conclusions: Despite proven effectiveness against severe outcomes, COVID-19 antiviral uptake remains low among those with SARS-CoV-2 infection in the United States. Further outreach to providers and patients to improve awareness of COVID-19 oral antivirals and indications is needed.

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

This study used repeat serologic testing to estimate infection rates and risk factors in two overlapping cohorts of SARS-CoV-2 N protein seronegative U.S. adults. One mostly unvaccinated sub-cohort was tracked from April 2020 to March 2021 (pre-vaccine/wild-type era, n = 3421), and the other, mostly vaccinated cohort, from March 2021 to June 2022 (vaccine/variant era, n = 2735). Vaccine uptake was 0.53% and 91.3% in the pre-vaccine and vaccine/variant cohorts, respectively. Corresponding seroconversion rates were 9.6 and 25.7 per 100 person-years. In both cohorts, sociodemographic and epidemiologic risk factors for infection were similar, though new risk factors emerged in the vaccine/variant era, such as having a child in the household. Despite higher incidence rates in the vaccine/variant cohort, vaccine boosters, masking, and social distancing were associated with substantially reduced infection risk, even through major variant surges.

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

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.

The prevalence of SARS-CoV-2 infection and other public health outcomes during the BA.2/BA.2.12.1 surge, New York City, April-May 2022.

BACKGROUND: Routine case surveillance data for SARS-CoV-2 are incomplete, unrepresentative, missing key variables of interest, and may be increasingly unreliable for timely surge detection and understanding the true burden of infection. METHODS: We conducted a cross-sectional survey of a representative sample of 1030 New York City (NYC) adult residents ≥18 years on May 7-8, 2022. We estimated the prevalence of SARS-CoV-2 infection during the preceding 14-day period. Respondents were asked about SARS-CoV-2 testing, testing outcomes, COVID-like symptoms, and contact with SARS-CoV-2 cases. SARS-CoV-2 prevalence estimates were age- and sex-adjusted to the 2020 U.S. POPULATION: We triangulated survey-based prevalence estimates with contemporaneous official SARS-CoV-2 counts of cases, hospitalizations, and deaths, as well as SARS-CoV-2 wastewater concentrations. RESULTS: We show that 22.1% (95% CI 17.9-26.2%) of respondents had SARS-CoV-2 infection during the two-week study period, corresponding to ~1.5 million adults (95% CI 1.3-1.8 million). The official SARS-CoV-2 case count during the study period is 51,218. Prevalence is estimated at 36.6% (95% CI 28.3-45.8%) among individuals with co-morbidities, 13.7% (95% CI 10.4-17.9%) among those 65+ years, and 15.3% (95% CI 9.6-23.5%) among unvaccinated persons. Among individuals with a SARS-CoV-2 infection, hybrid immunity (history of both vaccination and infection) is 66.2% (95% CI 55.7-76.7%), 44.1% (95% CI 33.0-55.1%) were aware of the antiviral nirmatrelvir/ritonavir, and 15.1% (95% CI 7.1-23.1%) reported receiving it. Hospitalizations, deaths and SARS-CoV-2 virus concentrations in wastewater remained well below that during the BA.1 surge. CONCLUSIONS: Our findings suggest that the true magnitude of NYC's BA.2/BA.2.12.1 surge may have been vastly underestimated by routine case counts and wastewater surveillance. Hybrid immunity, bolstered by the recent BA.1 surge, likely limited the severity of the BA.2/BA.2.12.1 surge.

It is difficult to assess the true prevalence of SARS-CoV-2, the virus that causes COVID-19, due to changes in testing practices and behaviors, including increasing at-home testing and decreasing healthcare provider-based testing. We conducted a population-representative survey in New York City to estimate the prevalence of SARS-CoV-2 during the second Omicron surge in spring 2022. We compared survey-based SARS-CoV-2 prevalence estimates with data on diagnosed cases, hospitalizations, deaths, and SARS-CoV-2 concentration in wastewater. Our survey-based estimates were nearly 30 times higher than official case counts and estimates of immunity among those with active infection were high. Taken together, our results suggest that the magnitude of the second Omicron surge was likely significantly underestimated, and high levels of immunity likely prevented a major surge in hospitalizations/deaths. Our findings might inform future work on COVID-19 surveillance and how to mitigate its spread.

Food Insecurity During the First Year of COVID-19: Employment and Sociodemographic Factors Among Participants in the CHASING COVID Cohort Study.

OBJECTIVE: While much has been reported about the impact of the COVID-19 pandemic on food insecurity, longitudinal data and the variability experienced by people working in various industries are limited. This study aims to further characterize people experiencing food insecurity during the pandemic in terms of employment, sociodemographic characteristics, and degree of food insecurity. METHODS: The study sample consisted of people enrolled in the Communities, Households and SARS-CoV-2 Epidemiology (CHASING) COVID Cohort Study from visit 1 (April-July 2020) through visit 7 (May-June 2021). We created weights to account for participants with incomplete or missing data. We used descriptive statistics and logistic regression models to determine employment and sociodemographic correlates of food insecurity. We also examined patterns of food insecurity and use of food support programs. RESULTS: Of 6740 participants, 39.6% (n = 2670) were food insecure. Non-Hispanic Black and Hispanic (vs non-Hispanic White) participants, participants in households with children (vs no children), and participants with lower (vs higher) income and education levels had higher odds of food insecurity. By industry, people employed in construction, leisure and hospitality, and trade, transportation, and utilities industries had the highest prevalence of both food insecurity and income loss. Among participants reporting food insecurity, 42.0% (1122 of 2670) were persistently food insecure (≥4 consecutive visits) and 43.9% (1172 of 2670) did not use any food support programs. CONCLUSIONS: The pandemic resulted in widespread food insecurity in our cohort, much of which was persistent. In addition to addressing sociodemographic disparities, future policies should focus on the needs of those working in industries vulnerable to economic disruption and ensure those experiencing food insecurity can access food support programs for which they are eligible.

The prevalence of SARS-CoV-2 infection and long COVID in U.S. adults during the BA.4/BA.5 surge, June-July 2022.

Due to changes in SARS-CoV-2 testing practices, passive case-based surveillance may be an increasingly unreliable indicator for monitoring the burden of SARS-CoV-2, especially during surges. We conducted a cross-sectional survey of a population-representative sample of 3042 U.S. adults between June 30 and July 2, 2022, during the Omicron BA.4/BA.5 surge. Respondents were asked about SARS-CoV-2 testing and outcomes, COVID-like symptoms, contact with cases, and experience with prolonged COVID-19 symptoms following prior infection. We estimated the weighted age and sex-standardized SARS-CoV-2 prevalence, during the 14-day period preceding the interview. We estimated age and gender adjusted prevalence ratios (aPR) for current SARS-CoV-2 infection using a log-binomial regression model. An estimated 17.3% (95% CI 14.9, 19.8) of respondents had SARS-CoV-2 infection during the two-week study period-equating to 44 million cases as compared to 1.8 million per the CDC during the same time period. SARS-CoV-2 prevalence was higher among those 18-24 years old (aPR 2.2, 95% CI 1.8, 2.7) and among non-Hispanic Black (aPR 1.7, 95% CI 1.4,2.2) and Hispanic adults (aPR 2.4, 95% CI 2.0, 2.9). SARS-CoV-2 prevalence was also higher among those with lower income (aPR 1.9, 95% CI 1.5, 2.3), lower education (aPR 3.7 95% CI 3.0,4.7), and those with comorbidities (aPR 1.6, 95% CI 1.4, 2.0). An estimated 21.5% (95% CI 18.2, 24.7) of respondents with a SARS-CoV-2 infection >4 weeks prior reported long COVID symptoms. The inequitable distribution of SARS-CoV-2 prevalence during the BA.4/BA.5 surge will likely drive inequities in the future burden of long COVID.

Modeling angiogenesis in the human brain in a tissue-engineered post-capillary venule.

Angiogenesis plays an essential role in embryonic development, organ remodeling, wound healing, and is also associated with many human diseases. The process of angiogenesis in the brain during development is well characterized in animal models, but little is known about the process in the mature brain. Here, we use a tissue-engineered post-capillary venule (PCV) model incorporating stem cell derived induced brain microvascular endothelial-like cells (iBMECs) and pericyte-like cells (iPCs) to visualize the dynamics of angiogenesis. We compare angiogenesis under two conditions: in response to perfusion of growth factors and in the presence of an external concentration gradient. We show that both iBMECs and iPCs can serve as tip cells leading angiogenic sprouts. More importantly, the growth rate for iPC-led sprouts is about twofold higher than for iBMEC-led sprouts. Under a concentration gradient, angiogenic sprouts show a small directional bias toward the high growth factor concentration. Overall, pericytes exhibited a broad range of behavior, including maintaining quiescence, co-migrating with endothelial cells in sprouts, or leading sprout growth as tip cells.

Psychosocial Stressors and Maternal Mental Health in the U.S. During the First Wave of the COVID-19 Pandemic: A Cross-Sectional Analysis.

OBJECTIVES: The COVID pandemic has had widespread impacts on maternal mental health. This research aims to examine the relationship between psychosocial stressors and symptoms of depression and anxiety and the extent to which emotional support or resilient coping moderates the relationship between psychosocial stressors and maternal mental health during the first wave of the COVID pandemic. METHODS: This analysis includes data collected in October and November 2020 from a geographically and sociodemographically diverse sample of 776 mothers in the U.S. with children ≤ 18 years of age. Log binomial models were used to estimate the association between moderate or severe symptoms of anxiety and depression and psychosocial stressors. RESULTS: Symptoms of moderate or severe anxiety and depression were reported by 37.5% and 37.6% of participants, respectively. Moderate (aRR 2.76 [95% CI 1.87, 4.07]) and high (aRR 4.95 [95% CI 3.40, 7.20]) levels of perceived stress were associated with greater risk of moderate or severe anxiety symptoms. Moderate and high levels of parental burnout were also associated with greater prevalence of moderate or severe anxiety symptoms in multivariable models. Results were similar when examining the relationship among stress, parental burnout, and depressive symptoms. Neither resilient coping nor social support modified the relationship between psychosocial stressors and mental health. CONCLUSIONS FOR PRACTICE: Evidence-based strategies to reduce stress and parental burnout and improve the mental health of mothers are urgently needed. Strategies focused on bolstering coping and social support may be insufficient to improve maternal mental health during acute public health emergencies.

Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting.

BACKGROUND: It is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups. METHODS: We conducted a retrospective study in patients ≥12 years who underwent testing for SARS-CoV-2 virus from April 14 through October 25, 2021, at urgent care centers in the New York metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n = 474,805), partially vaccinated (n = 87,834), and unvaccinated (n = 369,333) patients, adjusted for demographic factors and calendar time. RESULTS: VE against symptomatic infection after 2 doses of mRNA vaccine was 96% (95% Confidence Interval: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12-15-year-olds (85%; [95% CI: 81%, 88%]) was higher compared to older age groups (<65% for all other age groups). VE estimates did not differ by sex and race/ethnicity. VE against symptomatic infection was the highest for individuals with a prior infection followed by full vaccination. VE against symptomatic infection after the 2-dose mRNA-1273 vaccine (82% [95% CI: 80%, 84%]) was higher compared to the BNT162b2 vaccine (76% [95% CI: 74%, 78%]) in the delta period. VE after 1-dose of the Ad26.COV2.S vaccine was the lowest compared to other vaccines (19% [95% CI: 15%, 23%]) in the delta period. CONCLUSIONS: VE against infection after two doses of the mRNA vaccines was high initially, but significantly reduced against the delta variant for both FDA-approved vaccines.

The Epidemiology of Long Coronavirus Disease in US Adults.

BACKGROUND: We estimated the prevalence of long COVID and impact on daily living among a representative sample of adults in the United States. METHODS: We conducted a population-representative survey, 30 June-2 July 2022, of a random sample of 3042 US adults aged 18 years or older and weighted to the 2020 US population. Using questions developed by the UK's Office of National Statistics, we estimated the prevalence of long COVID, by sociodemographics, adjusting for gender and age. RESULTS: An estimated 7.3% (95% confidence interval: 6.1-8.5%) of all respondents reported long COVID, corresponding to approximately 18 828 696 adults. One-quarter (25.3% [18.2-32.4%]) of respondents with long COVID reported their day-to-day activities were impacted "a lot" and 28.9% had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection more than 12 months ago. The prevalence of long COVID was higher among respondents who were female (adjusted prevalence ratio [aPR]: 1.84 [1.40-2.42]), had comorbidities (aPR: 1.55 [1.19-2.00]), or were not (vs were) boosted (aPR: 1.67 [1.19-2.34]) or not vaccinated (vs boosted) (aPR: 1.41 [1.05-1.91]). CONCLUSIONS: We observed a high burden of long COVID, substantial variability in prevalence of SARS-CoV-2, and risk factors unique from SARS-CoV-2 risk, suggesting areas for future research. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID.

Severe Acute Respiratory Syndrome Coronavirus 2 Incidence and Risk Factors in a National, Community-Based Prospective Cohort of US Adults.

BACKGROUND: Prospective cohort studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence complement case-based surveillance and cross-sectional seroprevalence surveys. METHODS: We estimated the incidence of SARS-CoV-2 infection in a national cohort of 6738 US adults, enrolled in March-August 2020. Using Poisson models, we examined the association of social distancing and a composite epidemiologic risk score with seroconversion. The risk score was created using least absolute shrinkage selection operator (LASSO) regression to identify factors predictive of seroconversion. The selected factors were household crowding, confirmed case in household, indoor dining, gathering with groups of ≥10, and no masking in gyms or salons. RESULTS: Among 4510 individuals with ≥1 serologic test, 323 (7.3% [95% confidence interval (CI), 6.5%-8.1%]) seroconverted by January 2021. Among 3422 participants seronegative in May-September 2020 and retested from November 2020 to January 2021, 161 seroconverted over 1646 person-years of follow-up (9.8 per 100 person-years [95% CI, 8.3-11.5]). The seroincidence rate was lower among women compared with men (incidence rate ratio [IRR], 0.69 [95% CI, .50-.94]) and higher among Hispanic (2.09 [1.41-3.05]) than white non-Hispanic participants. In adjusted models, participants who reported social distancing with people they did not know (IRR for always vs never social distancing, 0.42 [95% CI, .20-1.0]) and with people they knew (IRR for always vs never, 0.64 [.39-1.06]; IRR for sometimes vs never, 0.60 [.38-.96]) had lower seroconversion risk. Seroconversion risk increased with epidemiologic risk score (IRR for medium vs low score, 1.68 [95% CI, 1.03-2.81]; IRR for high vs low score, 3.49 [2.26-5.58]). Only 29% of those who seroconverted reported isolating, and only 19% were asked about contacts. CONCLUSIONS: Modifiable risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the United States.

Estimating the Period Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During the Omicron (BA.1) Surge in New York City (NYC), 1 January to 16 March 2022.

In a population-based survey of adults in New York City, we assessed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests (including via exclusive at-home testing) and possible cases among untested respondents. An estimated 27.4% (95% confidence interval [CI]: 22.8%-32.0%) or 1.8 million adults (95% CI: 1.6-2.1 million) had SARS-CoV-2 infection between 1 January and 16 March 2022.

The Importance of Incorporating At-Home Testing Into SARS-CoV-2 Point Prevalence Estimates: Findings From a US National Cohort, February 2022.

BACKGROUND: Passive, case-based surveillance underestimates the true extent of active infections in the population due to undiagnosed and untested cases, the exclusion of probable cases diagnosed point-of-care rapid antigen tests, and the exclusive use of at-home rapid tests which are not reported as part of case-based surveillance. The extent in which COVID-19 surveillance may be underestimating the burden of infection is likely due to time-varying factors such as decreased test-seeking behaviors and increased access to and availability of at-home testing. OBJECTIVE: The objective of this study is to estimate the prevalence of SARS-CoV-2 based on different definitions of a case to ascertain the extent to which cases of SARS-CoV-2 may be underestimated by case-based surveillance. METHODS: A survey on COVID-19 exposure, infection, and testing was administered to calculate point prevalence of SARS-CoV-2 among a diverse sample of cohort adults from February 8, 2022, to February 22, 2022. Three-point prevalence estimates were calculated among the cohort, as follows: (1) proportion positives based on polymerase chain reaction (PCR) and rapid antigen tests; (2) proportion positives based on testing exclusively with rapid at-home tests; and (3) proportion of probable undiagnosed cases. Test positivity and prevalence differences across booster status were also examined. RESULTS: Among a cohort of 4328, there were a total of 644 (14.9%) cases. The point prevalence estimate based on PCR or rapid antigen tests was 5.5% (95% CI 4.8%-6.2%), 3.7% (95% CI 3.1%-4.2%) based on at-home rapid tests, and 5.7% (95% CI 5.0%-6.4%) based on the case definition of a probable case. The total point prevalence across all definitions was 14.9% (95% CI 13.8%-16.0%). The percent positivity among PCR or rapid tests was 50.2%. No statistically significant differences were observed in prevalence between participants with a COVID-19 booster compared to fully vaccinated and nonboosted participants except among exclusive at-home rapid testers. CONCLUSIONS: Our findings suggest a substantial number of cases were missed by case-based surveillance systems during the Omicron B.1.1.529 surge, when at-home testing was common. Point prevalence surveys may be a rapid tool to be used to understand SARS-CoV-2 prevalence and would be especially important during case surges to measure the scope and spread of active infections in the population.

Racial/Ethnic Disparities in Exposure, Disease Susceptibility, and Clinical Outcomes during COVID-19 Pandemic in National Cohort of Adults, United States.

We examined racial/ethnic disparities for COVID-19 seroconversion and hospitalization within a prospective cohort (n = 6,740) in the United States enrolled in March 2020 and followed-up through October 2021. Potential SARS-CoV-2 exposure, susceptibility to COVID-19 complications, and access to healthcare varied by race/ethnicity. Hispanic and Black non-Hispanic participants had more exposure risk and difficulty with healthcare access than white participants. Participants with more exposure had greater odds of seroconversion. Participants with more susceptibility and more barriers to healthcare had greater odds of hospitalization. Race/ethnicity positively modified the association between susceptibility and hospitalization. Findings might help to explain the disproportionate burden of SARS-CoV-2 infections and complications among Hispanic/Latino/a and Black non-Hispanic persons. Primary and secondary prevention efforts should address disparities in exposure, vaccination, and treatment for COVID-19.

Engineering the human blood-brain barrier at the capillary scale using a double-templating technique.

In vitro blood-brain barrier (BBB) models have played an important role in studying processes such as immune cell trafficking and drug delivery, as well as contributing to the understanding of mechanisms of disease progression. Many biological and pathological processes in the cerebrovasculature occur in capillaries and hence the lack of robust hierarchical models at the capillary scale is a major roadblock in BBB research. Here we report on a double-templating technique for engineering hierarchical BBB models with physiological barrier function at the capillary scale. We first demonstrate the formation of hierarchical vascular networks using human umbilical vein endothelial cells. We then characterize barrier function in a BBB model using brain microvascular endothelial-like cells (iBMECs) differentiated from induced pluripotent stem cells (iPSCs). Finally, we characterize immune cell adhesion and transmigration in response to perfusion with the inflammatory cytokine tumor necrosis factor-alpha, and show that we can recapitulate capillary-scale effects, such as leukocyte plugging, observed in mouse models. Our double-templated hierarchical model enables the study of a wide range of biological and pathological processes related to the human BBB.

Household factors and the risk of severe COVID-like illness early in the U.S. pandemic.

OBJECTIVE: To investigate the role of children in the home and household crowding as risk factors for severe COVID-19 disease. METHODS: We 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. RESULTS: In 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. CONCLUSION: Early 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.