The Survey of the Health of Wisconsin (SHOW) Program: An Infrastructure for Advancing Population Health.

Introduction: The Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of (1) providing a timely and accurate picture of the health of the state residents; and (2) serving as an agile resource infrastructure for ancillary studies. Today, the SHOW program continues to serve as a unique and vital population health research infrastructure for advancing public health. Methods: SHOW currently includes 5,846 adult and 980 minor participants recruited between 2008 and 2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1,957 adults (age ≥18 years) and 645 children (age 0-17). WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consists of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee, Wisconsin. Findings to Date: The SHOW resource provides unique spatially granular and timely data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures. Discussion: The SHOW cohort and resource is available for continued follow-up and ancillary studies including longitudinal public health monitoring, translational biomedical research, environmental health, aging, microbiome and COVID-19 research.

Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2.

Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti-SARS- CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (n = 113) and 3 mo (n = 79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 Ags, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never-before-assessed COVID-19 symptoms, that consistently correlate with high anti-SARS-CoV-2 Ab levels. We detected anti-SARS-CoV-2 Abs in 98% of COVID-19 convalescent subjects 5 wk after symptom resolution, and Ab levels did not decline at 3 mo. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 Ab levels. Moreover, we report for the first time (to our knowledge) that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti-SARS-CoV-2 Ab levels. Our results provide robust and new insights into the development and persistence of anti-SARS-CoV-2 Abs.

The impact of vaccination to control COVID-19 burden in the United States: A simulation modeling approach.

INTRODUCTION: Vaccination programs aim to control the COVID-19 pandemic. However, the relative impacts of vaccine coverage, effectiveness, and capacity in the context of nonpharmaceutical interventions such as mask use and physical distancing on the spread of SARS-CoV-2 are unclear. Our objective was to examine the impact of vaccination on the control of SARS-CoV-2 using our previously developed agent-based simulation model. METHODS: We applied our agent-based model to replicate COVID-19-related events in 1) Dane County, Wisconsin; 2) Milwaukee metropolitan area, Wisconsin; 3) New York City (NYC). We evaluated the impact of vaccination considering the proportion of the population vaccinated, probability that a vaccinated individual gains immunity, vaccination capacity, and adherence to nonpharmaceutical interventions. We estimated the timing of pandemic control, defined as the date after which only a small number of new cases occur. RESULTS: The timing of pandemic control depends highly on vaccination coverage, effectiveness, and adherence to nonpharmaceutical interventions. In Dane County and Milwaukee, if 50% of the population is vaccinated with a daily vaccination capacity of 0.25% of the population, vaccine effectiveness of 90%, and the adherence to nonpharmaceutical interventions is 60%, controlled spread could be achieved by June 2021 versus October 2021 in Dane County and November 2021 in Milwaukee without vaccine. DISCUSSION: In controlling the spread of SARS-CoV-2, the impact of vaccination varies widely depending not only on effectiveness and coverage, but also concurrent adherence to nonpharmaceutical interventions.

The landscape of antibody binding in SARS-CoV-2 infection.

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

Effect of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the United States : A Simulation Modeling Approach.

BACKGROUND: Across the United States, various social distancing measures were implemented to control the spread of coronavirus disease 2019 (COVID-19). However, the effectiveness of such measures for specific regions with varying population demographic characteristics and different levels of adherence to social distancing is uncertain. OBJECTIVE: To determine the effect of social distancing measures in unique regions. DESIGN: An agent-based simulation model. SETTING: Agent-based model applied to Dane County, Wisconsin; the Milwaukee metropolitan (metro) area; and New York City (NYC). PATIENTS: Synthetic population at different ages. INTERVENTION: Different times for implementing and easing social distancing measures at different levels of adherence. MEASUREMENTS: The model represented the social network and interactions among persons in a region, considering population demographic characteristics, limited testing availability, "imported" infections, asymptomatic disease transmission, and age-specific adherence to social distancing measures. The primary outcome was the total number of confirmed COVID-19 cases. RESULTS: The timing of and adherence to social distancing had a major effect on COVID-19 occurrence. In NYC, implementing social distancing measures 1 week earlier would have reduced the total number of confirmed cases from 203 261 to 41 366 as of 31 May 2020, whereas a 1-week delay could have increased the number of confirmed cases to 1 407 600. A delay in implementation had a differential effect on the number of cases in the Milwaukee metro area versus Dane County, indicating that the effect of social distancing measures varies even within the same state. LIMITATION: The effect of weather conditions on transmission dynamics was not considered. CONCLUSION: The timing of implementing and easing social distancing measures has major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach.

BACKGROUND: Across the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions. METHODS: We developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing. RESULTS: We found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31. CONCLUSION: The timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases.

Association of Mobile Phone Location Data Indications of Travel and Stay-at-Home Mandates With COVID-19 Infection Rates in the US.

Importance: A stay-at-home social distancing mandate is a key nonpharmacological measure to reduce the transmission rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), but a high rate of adherence is needed. Objective: To examine the association between the rate of human mobility changes and the rate of confirmed cases of SARS-CoV-2 infection. Design, Setting, and Participants: This cross-sectional study used daily travel distance and home dwell time derived from millions of anonymous mobile phone location data from March 11 to April 10, 2020, provided by the Descartes Labs and SafeGraph to quantify the degree to which social distancing mandates were followed in the 50 US states and District of Columbia and the association of mobility changes with rates of coronavirus disease 2019 (COVID-19) cases. Exposure: State-level stay-at-home orders during the COVID-19 pandemic. Main Outcomes and Measures: The main outcome was the association of state-specific rates of COVID-19 confirmed cases with the change rates of median travel distance and median home dwell time of anonymous mobile phone users. The increase rates are measured by the exponent in curve fitting of the COVID-19 cumulative confirmed cases, while the mobility change (increase or decrease) rates were measured by the slope coefficient in curve fitting of median travel distance and median home dwell time for each state. Results: Data from more than 45 million anonymous mobile phone devices were analyzed. The correlation between the COVID-19 increase rate and travel distance decrease rate was -0.586 (95% CI, -0.742 to -0.370) and the correlation between COVID-19 increase rate and home dwell time increase rate was 0.526 (95% CI, 0.293 to 0.700). Increases in state-specific doubling time of total cases ranged from 1.0 to 6.9 days (median [interquartile range], 2.7 [2.3-3.3] days) before stay-at-home orders were enacted to 3.7 to 30.3 days (median [interquartile range], 6.0 [4.8-7.1] days) after stay-at-home social distancing orders were put in place, consistent with pandemic modeling results. Conclusions and Relevance: These findings suggest that stay-at-home social distancing mandates, when they were followed by measurable mobility changes, were associated with reduction in COVID-19 spread. These results come at a particularly critical period when US states are beginning to relax social distancing policies and reopen their economies. These findings support the efficacy of social distancing and could help inform future implementation of social distancing policies should they need to be reinstated during later periods of COVID-19 reemergence.