BACKGROUND: Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance. METHODS: After calculating antinucleocapsid SARS-CoV-2 antibody seroprevalence using residual commercial laboratory serum specimens, 2 ratios were computed: (1) IHRs using coronavirus disease 2019 hospitalization data and (2) ICRs using Centers for Disease Control and Prevention surveillance data. Ratios were calculated across age groups (0-17, 18-49, 50-69, and ≥70 years) for 2 time periods (September-December 2021 [Delta] and December 2021-February 2022 [Omicron]). RESULTS: Pediatric IHRs increased from 76.7 during Delta to 258.4 during Omicron. Adult IHRs ranged from 3.0 (≥70 years) to 21.6 (18-49 years) during Delta and from 10.0 (≥70 years) to 119.1 (18-49 years) during Omicron. The pediatric ICR was lower during the Delta period (2.7) compared with the Omicron period (3.7). Adult ICRs (Delta: 1.1 [18-49 years] to 2.1 [70+ years]; Omicron: 2.2 [>70+ years] to 2.9 [50-69 years]) were lower than pediatric ICRs during both time periods. CONCLUSIONS: All age groups exhibited a lower proportion of infections associated with hospitalization in the Omicron period than the Delta period; the proportion of infections associated with hospitalization increased with each older age group. A lower proportion of SARS-CoV-2 infections were associated with reported cases in the Omicron period than in the Delta period among all age groups.

People with immunocompromising conditions (IC) are at increased risk of severe COVID-19 and death. These individuals show weaker immunogenicity following vaccination than individuals without IC, yet immunogenicity after SARS-CoV-2 infection is poorly understood. To address this gap, the presence of infection-induced antibodies in sera following a positive COVID-19 test result was compared between patients with and without IC. A commercial laboratory provided patient data gathered during July 2020-February 2022 on COVID-19 viral test results and antibody assay results, which included infection-induced (anti-N) antibody presence. Participants were categorized into having or not having IC based on if there was an indicative diagnostic code on their health record for a five-year period prior to the study period. Anti-N presence in sera from people with a positive COVID-19 test result was compared by IC status for four post-infection periods: 14-90, 91-180, 181-365, and 365+ days. A longitudinal, logistic regression produced adjusted odds ratios comparing anti-N prevalence among specimens with and without associated IC, adjusted for age, sex, residence in a metro area, and social vulnerability index (SVI) tertile. Data included 17,025 anti-N test results from 14,690 patients, 1,424 (9.7%) of which had at least one IC on record. In an adjusted comparison to patients without IC, patients with any IC were 0.61 times as likely to have infection-induced antibodies (99% CI: 0.40-0.93), during the 14-90 days following infection. Similar patterns were found when comparing people with two specific types of IC to people without any IC: (1) solid malignancies and (2) other intrinsic immune conditions. These findings stress the importance of prevention measures for people with IC, such as additional vaccination doses and consistent mask use before and after a documented infection.

We studied SARS-CoV-2 binding and neutralizing antibody titers among previously infected persons in the United States over time. We assayed SARS-CoV-2 spike protein receptor-binding domain and neutralizing antibody titers for a convenience sample of residual clinical serum specimens that had evidence of prior SARS-CoV-2 infection gathered during January 2021-February 2022. We correlated titers and examined them by age group (<18, 18-49, 50-64, and >65 years) across 4 different SARS-CoV-2 variant epochs. Among selected specimens, 30,967 had binding antibody titers and 744 had neutralizing titers available. Titers in specimens from children and adults correlated. In addition, mean binding antibody titers increased over time for all age groups, and mean neutralization titers increased over time for persons 16-49 and >65 years of age. Incorporating binding and neutralization antibody titers into infectious disease surveillance could provide a clearer picture of overall immunity and help target vaccination campaigns.

During September to December 2021, school mask policies to mitigate SARS-CoV-2 transmission varied throughout the US. We compared infection-induced seroprevalence estimates and estimated seroconversion among children residing in areas with and without school mask requirements. We estimated infection-induced seroprevalence among children in three age groups (5-17, 5-11, and 12-17 years) in areas with and without school district mask requirements for two time points: September 1-30, 2021 and December 15, 2021 to January 14, 2022. Robust Poisson regression models estimated population seroconversion over the semester among initially seronegative children. Permutation tests assessed for significant differences in the estimated population seroconversion due to incident infections by school district mask policy. Residing in an area with no school mask requirement was associated with higher infection-induced seroprevalence among children aged 5-17 years (adjusted prevalence ratio [aPR] = 1.18, 95% confidence interval [CI]: 1.10, 1.26), and those aged 5-11 years (aPR) = 1.21, 95% CI: 1.10, 1.32) and those aged 12-17 years (aPR = 1.16, 95% CI: 1.07, 1.26), compared with areas requiring masks in school. Estimated population seroconversion during the semester was also significantly higher among children in districts without mask policies than those with school mask requirements among all age groups (5-17 years: 23.7% vs 18.1%, P < 0.001; 5-11 years: 6.4% vs 4.5%, P = 0.002;12-17 years: 27.2% vs 21.0%, P < 0.001). During the U.S. Fall 2021 semester, areas with school mask requirements had lower infection-induced seroprevalence and an estimated lower proportion of seroconversion due to incident infection among school-aged children compared with areas without school mask requirements; causality cannot necessarily be inferred from these associations. IMPORTANCE: During the U.S. Fall 2021 school semester, the estimated proportion of previously uninfected school-aged children who experienced a first infection with SARS-CoV-2 was lower in areas where public school district policies required masks for all staff and students compared with areas where the school districts had no mask requirements. Because children are more likely than adults to experience asymptomatic or mild SARS-CoV-2 infections, the presence of infection-induced antibodies is a more accurate measure of infection history than clinical testing. The proportion of children with these antibodies (i.e., seroprevalence) can improve our understanding of SARS-CoV-2 by detecting more infections and eliminating potential bias due to local testing and reporting practices. Enhanced robustness of surveillance for respiratory infections in children, including records of mitigation policies in communities and schools, as well as seroprevalence data, would establish a better evidence base for policy decisions and response measures during future respiratory outbreaks.

We estimated monthly cross-sectional seroprevalence rates of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies to severe acute respiratory syndrome coronavirus 2 in two U.S. nationwide studies. The nationwide blood donor seroprevalence (NBDS) study included specimens from blood donors, while the nationwide commercial laboratory seroprevalence (NCLS) study included residual serum specimens tested in commercial laboratories for reasons unrelated to the assessment of coronavirus disease 2019 infection. In September-December 2021, specimens collected from both nationwide studies were tested for anti-N antibodies. In September-October 2021, specimens from both studies within a five-state area were tested for anti-S antibodies. We used raking methods to adjust all seroprevalence estimates by the population distribution of key demographics in included states. Seroprevalence estimates of each antibody type were compared across the two studies for specimens drawn in the same U.S. states during the same time period. Our analysis revealed that over a 4-month period, national NCLS monthly anti-N estimates were 0.5-1.9 percentage points higher than NBDS estimates. In contrast, across five states during a 2-month period, NBDS anti-S estimates were 7.6 and 8.2 percentage points higher than NCLS estimates. The observed differences in seroprevalence estimates between the NBDS and NCLS studies may be attributed to variations in the characteristics of the study sample populations, particularly with respect to health status, health behaviors, and vaccination status. These differences should be considered in the interpretation of seroprevalence study results based on blood donors or commercial lab residual specimens. IMPORTANCE: This study was the first systematic comparison between two nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies which estimated seroprevalence, or the proportion of the population with antibodies to the virus, using differing convenience sample populations. One study tested blood donor specimens; the other study tested specimens left over from clinical blood tests. The seroprevalence of anti-nucleocapsid and anti-spike antibodies was compared in the same states during the same months with statistical adjustments based on state demographics. Similar anti-nucleocapsid antibody seroprevalence estimates produced by two independent studies using differing convenience samples build confidence in the generalizability of their anti-nucleocapsid findings. Due to high blood donor vaccine rates, blood donor SARS-CoV-2 anti-spike antibody estimates might overestimate general population seroprevalence, an important consideration for interpreting national seroprevalence study results. Furthermore, because laboratory residuals and blood donations are two common sources of specimens for seroprevalence studies, study findings may be informative for other respiratory virus seroepidemiology studies.

OBJECTIVES: People with disabilities, people experiencing homelessness, and people who have substance use disorders face unique health challenges. Gaps in public health surveillance data limit the identification of public health needs of these groups and data-driven action. This study aimed to identify current practices, challenges, and opportunities for collecting and reporting COVID-19 surveillance data for these populations. METHODS: We used a rapid qualitative assessment to explore COVID-19 surveillance capacities. From July through October 2021, we virtually interviewed key informants from the Centers for Disease Control and Prevention, state and local health departments, and health care providers across the United States. We thematically analyzed and contextualized interview notes, peer-reviewed articles, and participant documents using a literature review. RESULTS: We identified themes centered on foundational structural and systems issues that hinder actionable surveillance data for these and other populations that are disproportionately affected by multiple health conditions. Qualitative data analysis of 61 interviews elucidated 4 primary challenges: definitions and policies, resources, data systems, and articulation of the purpose of data collection to these groups. Participants noted the use of multisector partnerships, automated data collection and integration, and data scorecards to circumvent challenges. CONCLUSIONS: This study highlights the need for multisector, systematic improvements in surveillance data collection and reporting to advance health equity. Improvements must be buttressed with adequate investment in data infrastructure and promoted through clear communication of how data are used to protect health.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

OBJECTIVE: We conducted a national US study of SARS-CoV-2 seroprevalence by Social Vulnerability Index (SVI) that included pediatric data and compared the Delta and Omicron periods during the COVID-19 pandemic. The objective of the current study was to assess the association between SVI and seroprevalence of infection-induced SARS-CoV-2 antibodies by period (Delta vs Omicron) and age group. METHODS: We used results of infection-induced SARS-CoV-2 antibody assays of clinical sera specimens (N = 406 469) from 50 US states from September 2021 through February 2022 to estimate seroprevalence overall and by county SVI tercile. Bivariate analyses and multilevel logistic regression models assessed the association of seropositivity with SVI and its themes by age group (0-17, ≥18 y) and period (Delta: September-November 2021; Omicron: December 2021-February 2022). RESULTS: Aggregate infection-induced SARS-CoV-2 antibody seroprevalence increased at all 3 SVI levels; it ranged from 25.8% to 33.5% in September 2021 and from 53.1% to 63.5% in February 2022. Of the 4 SVI themes, socioeconomic status had the strongest association with seroprevalence. During the Delta period, we found significantly more infections per reported case among people living in a county with high SVI (odds ratio [OR] = 2.76; 95% CI, 2.31-3.21) than in a county with low SVI (OR = 1.65; 95% CI, 1.33-1.97); we found no significant difference during the Omicron period. Otherwise, findings were consistent across subanalyses by age group and period. CONCLUSIONS: Among both children and adults, and during both the Delta and Omicron periods, counties with high SVI had significantly higher SARS-CoV-2 antibody seroprevalence than counties with low SVI did. These disparities reinforce SVI's value in identifying communities that need tailored prevention efforts during public health emergencies and resources to recover from their effects.

BACKGROUND: Cleaning practices and hand hygiene are important behaviors to prevent and control the spread of infectious disease, especially in congregate settings. This project explored hygiene- and cleaning-related experiences in shelters serving people experiencing homelessness (PEH) during May-June 2020 of the COVID-19 pandemic. METHODS: We conducted qualitative, in-depth interviews by phone with 22 staff from six shelters in Atlanta, Georgia. The interview guide included questions about cleaning routines, cleaning barriers and facilitators, cleaning promotion, hand hygiene promotion, and hand hygiene barriers and facilitators. We analyzed interview transcripts using thematic analysis. RESULTS: Multiple individuals, such as shelter individuals (clients), volunteers, and staff, played a role in shelter cleaning. Staff reported engaging in frequent hand hygiene and cleaning practices. Barriers to cleaning included staffing shortages and access to cleaning supplies. Staff reported barriers (e.g., differing perceptions of cleanliness) for clients who were often involved in cleaning activities. Barriers to hand hygiene included limited time to wash hands, forgetting, and inconvenient handwashing facilities. Specific guidance about when and how to clean, and what supplies to use, were requested. CONCLUSION: During the early months of the COVID-19 pandemic, shelters serving PEH in the Atlanta-metro area needed resources and support to ensure sufficient staffing and supplies for cleaning activities. As part of future pandemic planning and outbreak prevention efforts, shelters serving PEH could benefit from specific guidance and training materials on cleaning and hand hygiene practices.

Public health problems cannot be addressed without timely and accurate data. However, data that provide insight into populations that may be at disproportionate risk for disease, including people experiencing homelessness, are insufficiently captured. Although the associations between homelessness and disease have been well documented,1-6 data on housing status are not universally or consistently collected in routine public health data.7 Improving collection of data on housing status in public health data collection efforts is necessary to address health disparities among people experiencing homelessness and advance health equity research and practice. | Collecting data related to homelessness and disease is complicated for several reasons, but one of the most salient reasons is that defining homelessness is challenging. Several federal agencies use their own definitions to identify people who might be eligible for assistance programs, creating confusion about which definition should be used for public health purposes. In addition, definitions of homelessness at federal agencies have changed over time, further complicating the collection of homelessness data. The US Department of Housing and Urban Development (HUD) defines homelessness as lacking a fixed, regular, and adequate nighttime residence8; this definition includes both people with a primary nighttime residence of a public or private place not meant for human habitation (eg, cars, parks, public spaces, abandoned buildings) and people residing in temporary shelters (eg, emergency homeless shelter, transitional housing). The US Department of Education (DOE) uses a broader lens, defining homelessness to include school-aged children whose housing situation meets the HUD criteria for homelessness while also including those who share housing with other people by doubling up or couch surfing; those who live in motels, hotels, or trailer parks; and those who are abandoned at hospitals.9

OBJECTIVES: To examine disparities by sex, age group, and race and ethnicity in COVID-19 confirmed cases, hospitalizations, and deaths among incarcerated people and staff in correctional facilities. METHODS: Six U.S. jurisdictions reported data on COVID-19 confirmed cases, hospitalizations, and deaths stratified by sex, age group, and race and ethnicity for incarcerated people and staff in correctional facilities during March 1- July 31, 2020. We calculated incidence rates and rate ratios (RR) and absolute rate differences (RD) by sex, age group, and race and ethnicity, and made comparisons to the U.S. general population. RESULTS: Compared with the U.S. general population, incarcerated people and staff had higher COVID-19 case incidence (RR = 14.1, 95% CI = 13.9-14.3; RD = 6,692.2, CI = 6,598.8-6,785.5; RR = 6.0, CI = 5.7-6.3; RD = 2523.0, CI = 2368.1-2677.9, respectively); incarcerated people also had higher rates of COVID-19-related deaths (RR = 1.6, CI = 1.4-1.9; RD = 23.6, CI = 14.9-32.2). Rates of COVID-19 cases, hospitalizations, and deaths among incarcerated people and corrections staff differed by sex, age group, and race and ethnicity. The COVID-19 hospitalization (RR = 0.9, CI = 0.8-1.0; RD = -48.0, CI = -79.1- -16.8) and death rates (RR = 0.8, CI = 0.6-1.0; RD = -11.8, CI = -23.5- -0.1) for Black incarcerated people were lower than those for Black people in the general population. COVID-19 case incidence, hospitalizations, and deaths were higher among older incarcerated people, but not among staff. CONCLUSIONS: With a few exceptions, living or working in a correctional setting was associated with higher risk of COVID-19 infection and resulted in worse health outcomes compared with the general population; however, Black incarcerated people fared better than their U.S. general population counterparts.

Background and Objectives Case-based surveillance of pediatric COVID-19 cases underestimates the prevalence of SARS-CoV-2 infections among children and adolescents. Our objectives were to: 1) estimate monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years and 2) calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 14 U.S. states.Methods Using data from commercial laboratory seroprevalence surveys, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. Seroprevalence estimates were based on SARS-CoV-2 anti-nucleocapsid immunoassays from February to May 2021. We compared estimated numbers of children infected with SARS-CoV-2 by May 2021 to cumulative incidence of confirmed and probable COVID-19 cases from case-based surveillance, and calculated infection: case ratios by state and type of anti-SARS-CoV-2 nucleocapsid immunoassay used for seroprevalence testing.Results Analyses included 67,321 serum specimens tested for SARS-CoV-2 antibodies among children in 14 U.S. states. Estimated ratios of SARS-CoV-2 infections to reported confirmed and probable COVID-19 cases among children and adolescents varied by state and type of immunoassay, ranging from 0.8-13.3 in May 2021.Conclusions Through May 2021, the majority of children in selected states did not have detectable SARS-CoV-2 nucleocapsid antibodies. Case-based surveillance underestimated the number of children infected with SARS-CoV-2, however the predicted extent of the underestimate varied by state, immunoassay, and over time. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding for this work was supported by CDC (Atlanta, Georgia).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by Centers for Disease Control and Prevention and determined to be consistent with non human participant research activity. Informed consent was waived, as data were deidentified. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesDeidentified individual participant data will not be made available.CDCCenters of Disease Control and PreventionMIS-CMultisystem inflammatory syndrome in childrenEUAEmergency Use AuthorizationFDAU.S. Food and Drug AdministrationACIPAdvisory Committee on Immunizations PracticesNNucleocapsidSSpikeIgImmunoglobulinCIConfidence intervals

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

During the COVID-19 pandemic, renewal equation estimates of time-varying effective reproduction numbers were useful to policymakers in evaluating the need for and impact of mitigation measures. Our objective here is to illustrate the utility of mechanistic expressions for the basic and effective (or intrinsic and realized) reproduction numbers, [Formula: see text] and related quantities derived from a Susceptible-Exposed-Infectious-Removed (SEIR) model including features of COVID-19 that might affect transmission of SARS-CoV-2, including asymptomatic, pre-symptomatic, and symptomatic infections, with which people may be hospitalized. Expressions from homogeneous host population models can be analyzed to determine the effort needed to reduce [Formula: see text] from [Formula: see text] to 1 and contributions of modeled mitigation measures. Our model is stratified by age, 0-4, 5-9, …, 75+ years, and location, the 50 states plus District of Columbia. Expressions from such heterogeneous host population models include subpopulation reproduction numbers, contributions from the above-mentioned infectious states, metapopulation numbers, subpopulation contributions, and equilibrium prevalence. While the population-immunity at which [Formula: see text] has captured the popular imagination, the metapopulation [Formula: see text] could be attained in an infinite number of ways even if only one intervention (e.g., vaccination) were capable of reducing [Formula: see text] However, gradients of expressions derived from heterogeneous host population models,[Formula: see text] can be evaluated to identify optimal allocations of limited resources among subpopulations. We illustrate the utility of such analytical results by simulating two hypothetical vaccination strategies, one uniform and other indicated by [Formula: see text] as well as the actual program estimated from one of the CDC's nationwide seroprevalence surveys conducted from mid-summer 2020 through the end of 2021.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. METHODS: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. RESULTS: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. CONCLUSIONS: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance.

BACKGROUND: Sero-surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reveal trends and differences in subgroups and capture undetected or unreported infections that are not included in case-based surveillance systems. METHODS: Cross-sectional, convenience samples of remnant sera from clinical laboratories from 51 U.S. jurisdictions were assayed for infection-induced SARS-CoV-2 antibodies biweekly from October 25, 2020, to July 11, 2021, and monthly from September 6, 2021, to February 26, 2022. Test results were analyzed for trends in infection-induced, nucleocapsid-protein seroprevalence using mixed effects models that adjusted for demographic variables and assay type. FINDINGS: Analyses of 1,469,792 serum specimens revealed U.S. infection-induced SARS-CoV-2 seroprevalence increased from 8.0% (95% confidence interval (CI): 7.9%-8.1%) in November 2020 to 58.2% (CI: 57.4%-58.9%) in February 2022. The U.S. ratio of the change in estimated seroprevalence to the change in reported case prevalence was 2.8 (CI: 2.8-2.9) during winter 2020-2021, 2.3 (CI: 2.0-2.5) during summer 2021, and 3.1 (CI: 3.0-3.3) during winter 2021-2022. Change in seroprevalence to change in case prevalence ratios ranged from 2.6 (CI: 2.3-2.8) to 3.5 (CI: 3.3-3.7) by region in winter 2021-2022. INTERPRETATION: Ratios of the change in seroprevalence to the change in case prevalence suggest a high proportion of infections were not detected by case-based surveillance during periods of increased transmission. The largest increases in the seroprevalence to case prevalence ratios coincided with the spread of the B.1.1.529 (Omicron) variant and with increased accessibility of home testing. Ratios varied by region and season with the highest ratios in the midwestern and southern United States during winter 2021-2022. Our results demonstrate that reported case counts did not fully capture differing underlying infection rates and demonstrate the value of sero-surveillance in understanding the full burden of infection. Levels of infection-induced antibody seroprevalence, particularly spikes during periods of increased transmission, are important to contextualize vaccine effectiveness data as the susceptibility to infection of the U.S. population changes. FUNDING: This work was supported by the Centers for Disease Control and Prevention, Atlanta, Georgia.

BACKGROUND AND OBJECTIVES: Trends in estimates of US pediatric SARS-CoV-2 infection-induced seroprevalence from commercial laboratory specimens may overrepresent children with frequent healthcare needs. We examined seroprevalence trends and compared seroprevalence estimates by testing type and diagnostic coding. METHODS: Cross-sectional convenience samples of residual sera between September 2021 and February 2022 from 52 U.S. jurisdictions were assayed for infection-induced SARS-CoV-2 antibodies; monthly seroprevalence estimates were calculated by age group. Multivariate logistic analyses compared seroprevalence estimates for specimens associated with ICD-10 codes and laboratory orders indicating well-child care with estimates for other pediatric specimens. RESULTS: Infection-induced SARS-CoV-2 seroprevalence increased in each age group; from 30% to 68% (1-4 years), 38% to 77% (5-11 years), and 40% to 74% (12-17 years). On multivariate analysis, patients with well-child ICD-10 codes were seropositive more often than other patients aged 1-17 years (adjusted prevalence ratio [aPR] 1.04; 95% CI 1.02-1.07); children aged 9-11 years receiving standard lipid screening were seropositive more often than those receiving other laboratory tests (1.05; 1.02-1.08). CONCLUSIONS: Infection-induced seroprevalence more than doubled among children under 12 between September 2021 and February 2022, and increased 85% in adolescents. Differences in seroprevalence by care type did not substantially impact US pediatric seroprevalence estimates.

BACKGROUND: Systemic inequities may place people with disabilities at higher risk of severe COVID-19 illness or lower likelihood to be discharged home after hospitalization. We examined whether severity of COVID-19 hospitalization outcomes and disposition differ by disability status and disability type. METHODS: In a retrospective analysis of April 2020-November 2021 hospital-based administrative data among 745,375 people hospitalized with COVID-19 from 866 US hospitals, people with disabilities (n = 120,360) were identified via ICD-10-CM codes. Outcomes compared by disability status included intensive care admission, invasive mechanical ventilation (IMV), in-hospital mortality, 30-day readmission, length of stay, and disposition (discharge to home, long-term care facility (LTCF), or skilled nursing facility (SNF). RESULTS: People with disabilities had increased risks of IMV (aRR: 1.05; 95%CI: 1.03-1.08) and in-hospital mortality (1.04; 1.02-1.06) compared to those with no disability; risks were higher among people with intellectual and developmental disabilities (IDD) (IMV [1.34; 1.28-1.40], mortality [1.31; 1.26-1.37]) or mobility disabilities (IMV [1.13; 1.09-1.16], mortality [1.04; 1.01-1.07]). Risk of readmission was increased among people with any disability (1.23; 1.20-1.27) and each disability type. Risks of discharge to a LTCF (1.45, 1.39-1.49) or SNF (1.78, 1.74-1.81) were increased among community-dwelling people with each disability type. CONCLUSIONS: Severity of COVID-19 hospitalization outcomes vary by disability status and type; IDD and mobility disabilities were associated with higher risks of severe outcomes. Disparities such as differences in discharge disposition by disability status require further study which would be facilitated by standardized data on disability. Increased readmission across disability types indicates a need to improve discharge planning and support services.

Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling. They also provide the information needed to calculate age-specific forces of infection, attack rates, and - together with contact rates - age-specific probabilities of infection on contact between susceptible and infectious people. We modified the familiar Susceptible-Exposed-Infectious-Removed (SEIR) model to include features of the biology of COVID-19 that might affect transmission of SARS-CoV-2 and stratified by age and location. We consulted the primary literature or subject matter experts for contact rates and other parameter values. Using time-varying Oxford COVID-19 Government Response Tracker assessments of US state and DC efforts to mitigate the pandemic and compliance with non-pharmaceutical interventions (NPIs) from a YouGov survey fielded in the US during 2020, we estimate that the efficacy of social-distancing when possible and mask-wearing otherwise at reducing susceptibility or infectiousness was 31% during the fall of 2020. Initialized from seroprevalence among people having commercial laboratory tests for purposes other than SARS-CoV-2 infection assessments on 7 September 2020, our age- and location-stratified SEIR population model reproduces seroprevalence among members of the same population on 25 December 2020 quite well. Introducing vaccination mid-December 2020, first of healthcare and other essential workers, followed by older adults, people who were otherwise immunocompromised, and then progressively younger people, our metapopulation model reproduces seroprevalence among blood donors on 4 April 2021 less well, but we believe that the discrepancy is due to vaccinations being under-reported or blood donors being disproportionately vaccinated, if not both. As experimenting with reliable transmission models is the best way to assess the indirect effects of mitigation measures, we determined the impact of vaccination, conditional on NPIs. Results indicate that, during this period, vaccination substantially reduced infections, hospitalizations and deaths. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics."

Previous COVID-19 vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 from COVID-19-unvaccinated persons with detectable anti-SARS-CoV-2 antibodies. Neutralizing and binding antibody concentrations were severalfold lower in the unvaccinated study population compared to published concentrations at 28 days postvaccination. In this convenience sample, ~88% of neutralizing and ~63 to 86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection; ~30% of neutralizing and 1 to 14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. Our study not only supports observations of infection-induced immunity and current recommendations for vaccination postinfection to maximize protection against COVID-19, but also provides a large data set of pre-COVID-19 vaccination anti-SARS-CoV-2 antibody concentrations that will serve as an important comparator in the current setting of vaccine-induced and hybrid immunity. As new SARS-CoV-2 variants emerge and displace circulating virus strains, we recommend that standardized binding antibody assays that include spike protein-based antigens be utilized to estimate antibody concentrations correlated with protection from COVID-19. These estimates will be helpful in informing public health guidance, such as the need for additional COVID-19 vaccine booster doses to prevent symptomatic infection. IMPORTANCE Although COVID-19 vaccine efficacy (VE) studies have estimated antibody concentrations that correlate with protection from COVID-19, how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. We assessed quantitative neutralizing and binding antibody concentrations using standardized assays on serum specimens collected from COVID-19-unvaccinated persons with detectable antibodies. We found that most unvaccinated persons with qualitative antibody evidence of prior infection had quantitative antibody concentrations that met or exceeded concentrations associated with 70% VE against COVID-19. However, only a small proportion had antibody concentrations that met or exceeded concentrations associated with 90% VE, suggesting that persons with prior COVID-19 would benefit from vaccination to maximize protective antibody concentrations against COVID-19.

OBJECTIVES: To assess if state-issued nonpharmaceutical interventions (NPIs) are associated with reduced rates of SARS-CoV-2 infection as measured through anti-nucleocapsid (anti-N) seroprevalence, a proxy for cumulative prior infection that distinguishes seropositivity from vaccination). METHODS: Monthly anti-N seroprevalence during August 1, 2020 - March 30, 2021 was estimated using a nationwide blood donor serosurvey. Using multivariable logistic regression models, we measured the association of seropositivity and state-issued, county-specific NPIs for mask mandates, gathering bans, and bar closures. RESULTS: Compared with individuals living in a county with all three NPIs in place, the odds of having anti-N antibodies were 2.2 (95% CI: 2.0-2.3) times higher for people living in a county that did not have any of the three NPIs, 1.6 (95% CI: 1.5-1.7) times higher for people living in a county that only had a mask mandate and gathering ban policy, and 1.4 (95% CI: 1.3-1.5) times higher for people living in a county that had only a mask mandate. CONCLUSIONS: Consistent with studies assessing NPIs relative to COVID-19 incidence and mortality, the presence of NPIs were associated with lower SARS-CoV-2 seroprevalence indicating lower rates of cumulative infections. Multiple NPIs are likely more effective than single NPIs.

In December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, became predominant in the United States. Subsequently, national COVID-19 case rates peaked at their highest recorded levels.* Traditional methods of disease surveillance do not capture all COVID-19 cases because some are asymptomatic, not diagnosed, or not reported; therefore, the proportion of the population with SARS-CoV-2 antibodies (i.e., seroprevalence) can improve understanding of population-level incidence of COVID-19. This report uses data from CDC's national commercial laboratory seroprevalence study and the 2018 American Community Survey to examine U.S. trends in infection-induced SARS-CoV-2 seroprevalence during September 2021-February 2022, by age group.

Homelessness is a serious public health issue. The number of people experiencing homelessness (PEH) has been increasing since 2016; on a single night in January 2020, an estimated 580 000 people were experiencing homelessness in the United States, more than 225 000 of whom were unsheltered (ie, having a primary nighttime location that is not designated as a regular sleeping accommodation, such as on the streets or in abandoned buildings, vehicles, or encampments). 1 Compared with the general US population, PEH experience elevated rates of infectious and noninfectious disease and face 3 to 10 times higher mortality rates.2,3 In the United States, non-Hispanic Black people were 3.5 times more likely than non-Hispanic White people to experience homelessness. 4 American Indian/Alaska Native people also have disproportionately high rates of homelessness compared with non-Hispanic White people. 5

BACKGROUND: Case-based surveillance of pediatric coronavirus disease 2019 (COVID-19) cases underestimates the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children and adolescents. Our objectives were to estimate monthly SARS-CoV-2 antibody seroprevalence and calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 8 US states. METHODS: Using data from the Nationwide Commercial Laboratory Seroprevalence Survey, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. We calculated and compared cumulative incidence of SARS-CoV-2 infection extrapolated from population-standardized seroprevalence of antibodies to SARS-CoV-2, cumulative COVID-19 case reports since March 2020, and infection-to-case ratios among persons of all ages and children aged 0-17 years for each state. RESULTS: Of 41 583 residual serum specimens tested, children aged 0-4, 5-11, and 12-17 years accounted for 1619 (3.9%), 10 507 (25.3%), and 29 457 (70.8%), respectively. Median SARS-CoV-2 antibody seroprevalence among children increased from 8% (range, 6%-20%) in August 2020 to 37% (range, 26%-44%) in May 2021. Estimated ratios of SARS-CoV-2 infections to reported COVID-19 cases in May 2021 ranged by state from 4.7-8.9 among children and adolescents to 2.2-3.9 for all ages combined. CONCLUSIONS: Through May 2021 in selected states, the majority of children with serum specimens included in serosurveys did not have evidence of prior SARS-CoV-2 infection. Case-based surveillance underestimated the number of children infected with SARS-CoV-2 more than among all ages. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.

BACKGROUND: Most studies on health disparities during COVID-19 pandemic focused on reported cases and deaths, which are influenced by testing availability and access to care. This study aimed to examine SARS-CoV-2 antibody seroprevalence in the U.S. and its associations with race/ethnicity, rurality, and social vulnerability over time. METHODS: This repeated cross-sectional study used data from blood donations in 50 states and Washington, D.C. from July 2020 through June 2021. Donor ZIP codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its four themes were quantified using multivariate regression models. FINDINGS: Weighted seroprevalence differed significantly by race/ethnicity and rurality, and increased with increasing social vulnerability. During the study period, infection-induced seroprevalence increased from 1.6% to 27.2% and 3.7% to 20.0% in rural and urban counties, respectively, while rural counties had lower combined infection- and vaccination-induced seroprevalence (80.0% vs. 88.1%) in June 2021. Infection-induced seropositivity was associated with being Hispanic, non-Hispanic Black, and living in rural or higher socially vulnerable counties, after adjusting for demographic and geographic covariates. CONCLUSION: The findings demonstrated increasing SARS-CoV-2 seroprevalence in the U.S. across all geographic, demographic, and social sectors. The study illustrated disparities by race-ethnicity, rurality, and social vulnerability. The findings identified areas for targeted vaccination strategies and can inform efforts to reduce inequities and prepare for future outbreaks.

IMPORTANCE: People experiencing incarceration (PEI) and people experiencing homelessness (PEH) have an increased risk of COVID-19 exposure from congregate living, but data on their hospitalization course compared with that of the general population are limited. OBJECTIVE: To compare COVID-19 hospitalizations for PEI and PEH with hospitalizations among the general population. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used data from the Premier Healthcare Database on 3415 PEI and 9434 PEH who were evaluated in the emergency department or were hospitalized in more than 800 US hospitals for COVID-19 from April 1, 2020, to June 30, 2021. EXPOSURES: Incarceration or homelessness. MAIN OUTCOMES AND MEASURES: Hospitalization proportions were calculated. and outcomes (intensive care unit admission, invasive mechanical ventilation [IMV], mortality, length of stay, and readmissions) among PEI and PEH were compared with outcomes for all patients with COVID-19 (not PEI or PEH). Multivariable regression was used to adjust for potential confounders. RESULTS: In total, 3415 PEI (2952 men [86.4%]; mean [SD] age, 50.8 [15.7] years) and 9434 PEH (6776 men [71.8%]; mean [SD] age, 50.1 [14.5] years) were evaluated in the emergency department for COVID-19 and were hospitalized more often (2170 of 3415 [63.5%] PEI; 6088 of 9434 [64.5%] PEH) than the general population (624 470 of 1 257 250 [49.7%]) (P < .001). Both PEI and PEH hospitalized for COVID-19 were more likely to be younger, male, and non-Hispanic Black than the general population. Hospitalized PEI had a higher frequency of IMV (410 [18.9%]; adjusted risk ratio [aRR], 1.16; 95% CI, 1.04-1.30) and mortality (308 [14.2%]; aRR, 1.28; 95% CI, 1.11-1.47) than the general population (IMV, 88 897 [14.2%]; mortality, 84 725 [13.6%]). Hospitalized PEH had a lower frequency of IMV (606 [10.0%]; aRR, 0.64; 95% CI, 0.58-0.70) and mortality (330 [5.4%]; aRR, 0.53; 95% CI, 0.47-0.59) than the general population. Both PEI and PEH had longer mean (SD) lengths of stay (PEI, 9 [10] days; PEH, 11 [26] days) and a higher frequency of readmission (PEI, 128 [5.9%]; PEH, 519 [8.5%]) than the general population (mean [SD] length of stay, 8 [10] days; readmission, 28 493 [4.6%]). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, a higher frequency of COVID-19 hospitalizations for PEI and PEH underscored the importance of adhering to recommended prevention measures. Expanding medical respite may reduce hospitalizations in these disproportionately affected populations.

Native Hawaiian and Pacific Islander populations have been disproportionately affected by COVID-19 (1-3). Native Hawaiian, Pacific Islander, and Asian populations vary in language; cultural practices; and social, economic, and environmental experiences,(†) which can affect health outcomes (4).(§) However, data from these populations are often aggregated in analyses. Although data aggregation is often used as an approach to increase sample size and statistical power when analyzing data from smaller population groups, it can limit the understanding of disparities among diverse Native Hawaiian, Pacific Islander, and Asian subpopulations(¶) (4-7). To assess disparities in COVID-19 outcomes among Native Hawaiian, Pacific Islander, and Asian populations, a disaggregated, descriptive analysis, informed by recommendations from these communities,** was performed using race data from 21,005 COVID-19 cases and 449 COVID-19-associated deaths reported to the Hawaii State Department of Health (HDOH) during March 1, 2020-February 28, 2021.(††) In Hawaii, COVID-19 incidence and mortality rates per 100,000 population were 1,477 and 32, respectively during this period. In analyses with race categories that were not mutually exclusive, including persons of one race alone or in combination with one or more races, Pacific Islander persons, who account for 5% of Hawaii's population, represented 22% of COVID-19 cases and deaths (COVID-19 incidence of 7,070 and mortality rate of 150). Native Hawaiian persons experienced an incidence of 1,181 and a mortality rate of 15. Among subcategories of Asian populations, the highest incidences were experienced by Filipino persons (1,247) and Vietnamese persons (1,200). Disaggregating Native Hawaiian, Pacific Islander, and Asian race data can aid in identifying racial disparities among specific subpopulations and highlights the importance of partnering with communities to develop culturally responsive outreach teams(§§) and tailored public health interventions and vaccination campaigns to more effectively address health disparities.

Adults with disabilities, a group including >25% of U.S. adults (1), experience higher levels of mental health and substance use conditions and lower treatment rates than do adults without disabilities* (2,3). Survey data collected during April-September 2020 revealed elevated adverse mental health symptoms among adults with disabilities (4) compared with the general adult population (5). Despite disproportionate risk for infection with SARS-CoV-2, the virus that causes COVID-19, and COVID-19-associated hospitalization and mortality among some adults with disabilities (6), information about mental health and substance use in this population during the pandemic is limited. To identify factors associated with adverse mental health symptoms and substance use among adults with disabilities, the COVID-19 Outbreak Public Evaluation (COPE) Initiative(†) administered nonprobability-based Internet surveys to 5,256 U.S. adults during February-March 2021 (response rate = 62.1%). Among 5,119 respondents who completed a two-item disability screener, nearly one third (1,648; 32.2%) screened as adults with disabilities. These adults more frequently experienced symptoms of anxiety or depression (56.6% versus 28.7%, respectively), new or increased substance use (38.8% versus 17.5%), and suicidal ideation (30.6% versus 8.3%) than did adults without disabilities. Among all adults who had received a diagnosis of mental health or substance use conditions, adults with disabilities more frequently (42.6% versus 35.3%; p <0.001) reported that the pandemic made it harder for them to access related care or medication. Enhanced mental health and substance use screening among adults with disabilities and improved access to medical services are critical during public health emergencies such as the COVID-19 pandemic.

We examined disparities in cumulative incidence of severe acute respiratory syndrome coronavirus 2 by race/ethnicity, age, and sex in the United States during January 1-October 1, 2020. Hispanic/Latino and non-Hispanic Black, American Indian/Alaskan Native, and Native Hawaiian/other Pacific Islander persons had a substantially higher incidence of infection than non-Hispanic White persons.

SARS-CoV-2, the virus that causes COVID-19, can spread rapidly in prisons and can be introduced by staff members and newly transferred incarcerated persons (1,2). On September 28, 2020, the Wisconsin Department of Health Services (DHS) contacted CDC to report a COVID-19 outbreak in a state prison (prison A). During October 6-20, a CDC team investigated the outbreak, which began with 12 cases detected from specimens collected during August 17-24 from incarcerated persons housed within the same unit, 10 of whom were transferred together on August 13 and under quarantine following prison intake procedures (intake quarantine). Potentially exposed persons within the unit began a 14-day group quarantine on August 25. However, quarantine was not restarted after quarantined persons were potentially exposed to incarcerated persons with COVID-19 who were moved to the unit. During the subsequent 8 weeks (August 14-October 22), 869 (79.4%) of 1,095 incarcerated persons and 69 (22.6%) of 305 staff members at prison A received positive test results for SARS-CoV-2. Whole genome sequencing (WGS) of specimens from 172 cases among incarcerated persons showed that all clustered in the same lineage; this finding, along with others, demonstrated that facility spread originated with the transferred cohort. To effectively implement a cohorted quarantine, which is a harm reduction strategy for correctional settings with limited space, CDC's interim guidance recommendation is to serial test cohorts, restarting the 14-day quarantine period when a new case is identified (3). Implementing more effective intake quarantine procedures and available mitigation measures, including vaccination, among incarcerated persons is important to controlling transmission in prisons. Understanding and addressing the challenges faced by correctional facilities to implement medical isolation and quarantine can help reduce and prevent outbreaks.