Numerous studies have investigated vaccine-induced correlates of protection (CoP) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, but data on infection-induced CoP are limited. Given differences between vaccine- and infection-induced immune responses, in conjunction with low vaccination in many US populations, a better understanding of infection-induced CoP is needed. We used residual sera from a mid-2020 Rhode Island serosurvey of healthcare professionals (HCP) and corresponding state-collected SARS-CoV-2 testing data through February 2021 to generate an analytic cohort of HCP with a first SARS-CoV-2 infection prior to serosurvey blood collection and multiple viral tests after blood collection to assess for reinfection (defined as a positive viral test ≥90 days after their first positive). We tested sera for levels of IgG and IgA targeting ancestral spike (S), receptor-binding domain (RBD), or nucleocapsid (N). We used adjusted Cox proportional hazard ratios to assess the association between categorical antibody level and the risk of subsequent reinfection. Among 170 HCP included in this analysis (median age = 47 years; interquartile range: 35-55 years), 30 were reinfected during the analytic period. Adjusted Cox proportional hazard ratios indicated that higher levels of anti-S or anti-RBD IgG were significantly associated with a lower risk of reinfection. These findings support the use of anti-S or anti-RBD IgG levels as markers of immunologic protection, such as in population serosurveys, or immune-bridging studies in settings of high prevalence of prior infection.  IMPORTANCEThe measurement of antibodies in blood is a relatively simple process and commonly used to estimate overall levels of past infection in populations. But, if someone has antibodies, does this mean that they are protected from being infected again? And are people with higher levels of antibody better protected? There are good data in the literature exploring how antibodies from the coronavirus disease 2019 (COVID-19) vaccination are associated with protection. But, there is still a lot to learn about protection conferred by antibodies that develop after a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. In our study, we measure the levels of six different antibody types developed after infection and compare levels to the risk of subsequent infection to better understand which antibody types are best associated with protection. Our data are important for improving studies that use antibodies as proxies for protection, such as population immunity estimates, or those assessing new prevention products.

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.

During 2023, the Centers for Disease Control and Prevention (CDC) recommended the first respiratory syncytial virus (RSV) immunizations intended for widespread use in the United States to prevent severe RSV illness in infants and older adults. CDC, in collaboration with federal, public health, and academic partners, is conducting evaluations of real-world effectiveness of recommended RSV immunization products in the United States. Similar frameworks for evaluation are being applied to RSV vaccines and nirsevimab, a long-acting preventative monoclonal antibody, to estimate product effectiveness. The overall goal of CDC's RSV immunization effectiveness program is to generate timely and robust evidence through observational studies to inform immunization product policy decisions and other measures related to RSV prevention and control. CDC is evaluating effectiveness through high-quality, well-controlled observational studies leveraging a variety of platforms that provide robust data to inform policy decisions.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) causes substantial hospitalization in US infants. The Advisory Committee on Immunization Practices recommended nirsevimab in infants younger than 8 months born during or entering their first RSV season and for children aged 8 to 19 months at increased risk of RSV hospitalization in their second season. This study's objective was to evaluate the cost-effectiveness of nirsevimab in all infants in their first RSV season and in high-risk children in their second season. METHODS: We simulated healthcare utilization and deaths from RSV with and without nirsevimab among infants aged 0 to 7 months and those 8 to 19 months old over a single RSV season. Data came from published literature, US Food and Drug Administration approval documents, and epidemiologic surveillance data. We evaluated societal outcomes over a lifetime discounting at 3% and reporting in 2022 US dollars. Sensitivity and scenario analyses identified influential variables. RESULTS: We estimated that 107 253 outpatient visits, 38 204 emergency department visits, and 14 341 hospitalizations could be averted each year if half of the US birth cohort receives nirsevimab. This would cost $153 517 per quality-adjusted life year (QALY) saved. Nirsevimab in the second season for children facing a 10-fold higher risk of hospitalization would cost $308 468 per QALY saved. Sensitivity analyses showed RSV hospitalization costs, nirsevimab cost, and QALYs lost from RSV disease were the most influential parameters with cost-effectiveness ratios between cost-saving and $323 788 per QALY saved. CONCLUSIONS: Nirsevimab for infants may be cost-effective, particularly among those with higher risks and costs of RSV.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) commonly causes hospitalization among US infants. A maternal vaccine preventing RSV in infants, RSV bivalent prefusion F maternal vaccine (RSVpreF), was approved by the US Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices. Our objective was to evaluate the health benefits and cost-effectiveness of vaccinating pregnant persons in the United States using RSVpreF. METHODS: We simulated RSV infection and disease with and without seasonal RSVpreF vaccination in half of the pregnant persons in the annual US birth cohort during weeks 32 through 36 of gestation. Model inputs came from peer-reviewed literature, Food and Drug Administration records, and epidemiological surveillance databases. The results are reported using a societal perspective in 2022 US dollars for a 1-year time frame, discounting future health outcomes and costs at 3%. Sensitivity and scenario analyses were performed. RESULTS: Year-round maternal vaccination with RSVpreF would prevent 45 693 outpatient visits, 15 866 ED visits, and 7571 hospitalizations among infants each year. Vaccination had a societal incremental cost of $396 280 per quality-adjusted life-year (QALY) saved. Vaccination from September through January cost $163 513 per QALY saved. The most influential inputs were QALYs lost from RSV disease, the cost of the vaccine, and RSV-associated hospitalization costs; changes in these inputs yielded outcomes ranging from cost-saving to $800 000 per QALY saved. CONCLUSIONS: Seasonal maternal RSV vaccination designed to prevent RSV lower respiratory tract infection in infants may be cost-effective, particularly if administered to pregnant persons immediately before or at the beginning of the RSV season.

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with risk increasing with increasing age; outpatient antiviral treatment reduces the risk for these severe outcomes. Despite the proven benefit of COVID-19 antiviral treatment, information on differences in use among older adults with COVID-19 by age group is limited. Nonhospitalized patients aged ≥65 years with COVID-19 during April 2022-September 2023 were identified from the National Patient-Centered Clinical Research Network. Differences in use of antiviral treatment among patients aged 65-74, 75-89, and ≥90 years were assessed. Multivariable logistic regression was used to estimate the association between age and nonreceipt of antiviral treatment. Among 393,390 persons aged ≥65 years, 45.9% received outpatient COVID-19 antivirals, including 48.4%, 43.5%, and 35.2% among those aged 65-75, 76-89, and ≥90 years, respectively. Patients aged 75-89 and ≥90 years had 1.17 (95% CI = 1.15-1.19) and 1.54 (95% CI = 1.49-1.61) times the adjusted odds of being untreated, respectively, compared with those aged 65-74 years. Among 12,543 patients with severe outcomes, 2,648 (21.1%) had received an outpatient COVID-19 antiviral medication, compared with 177,874 (46.7%) of 380,847 patients without severe outcomes. Antiviral use is underutilized among adults ≥65 years; the oldest adults are least likely to receive treatment. To prevent COVID-19-associated morbidity and mortality, increased use of COVID-19 antiviral medications among older adults is needed.

PURPOSE: Limited information is known about the burden of Long COVID by occupation and industry. This study compares the occurrence of self-reported new long-term symptoms lasting 4 weeks or longer among blood donors with and without prior SARS-CoV-2 infection by occupation and industry. METHODS: The American Red Cross invited blood donors 18 years and older who donated during May 4-December 31, 2021 to participate in online surveys. New long-term symptoms lasting 4 weeks or longer were assessed by self-reported occurrence of any of 35 symptoms since March 2020. SARS-CoV-2 infection status was determined by serological testing and self-report. We describe the prevalence of new long-term symptoms by SARS-CoV-2 infection status. We calculate the difference in reported new long-term symptoms by SARS-CoV-2 infection status within occupation and industry categories. RESULTS: Data were collected from 27,907 employed adults - 9763 were previously infected and 18,234 were never infected with SARS-CoV-2. New long-term symptoms were more prevalent among those previously infected compared to the never-infected respondents (45% vs 24%, p < 0.05). Among all respondents, new long-term symptoms by occupation ranged from 26% (installation, maintenance, and repair) to 41% (healthcare support) and by industry ranged from 26% (mining) to 55% (accommodation and food services). New long-term neurological and other symptoms were commonly reported by those previously infected with SARS-CoV-2. DISCUSSION: New long-term symptoms are more prevalent among certain occupation and industry groups, which likely reflects differential exposure to SARS-CoV-2. These findings highlight potential need for workplace accommodations in a variety of occupational settings to address new long-term symptoms.

Respiratory syncytial virus (RSV) is the most common cause of hospitalization among U.S. infants. CDC recommends RSV vaccination for pregnant persons or administration of RSV antibody (nirsevimab) to infants aged <8 months to prevent RSV lower respiratory tract disease among infants. To determine maternal and infant RSV immunization coverage for the 2023-24 RSV season, CDC conducted an Internet panel survey during March 26-April 11, 2024. Among 678 women at 32-36 weeks' gestation during September 2023-January 2024, 32.6% reported receipt of an RSV vaccine any time during pregnancy. Among 866 women with an infant born during August 2023-March 2024, 44.6% reported receipt of nirsevimab by the infant. Overall, 55.8% of infants were protected by maternal RSV vaccine, nirsevimab, or both. Provider recommendation for maternal vaccination or infant nirsevimab was associated with higher immunization coverage, whereas lack of a provider recommendation was the main reason for not getting RSV immunization. The main reason for definitely or probably not getting nirsevimab for infants was concern about the long-term safety for the infant. Activities supporting providers to make RSV prevention recommendations and have informative conversations with patients might increase the proportion of infants protected against severe RSV disease. CDC and the American College of Obstetricians and Gynecologists have resources to assist providers in effectively communicating the importance of immunization.

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.

Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. METHODS: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021-August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14-59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. RESULTS: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). CONCLUSIONS: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.

Nucleocapsid antibody assays can be used to estimate SARS-CoV-2 infection prevalence in regions implementing spike-based COVID-19 vaccines. However, poor sensitivity of nucleocapsid antibody assays in detecting infection after vaccination has been reported. We derived a lower cutoff for identifying previous infections in a large blood donor cohort (N = 142,599) by using the Ortho VITROS Anti-SARS-CoV-2 Total-N Antibody assay, improving sensitivity while maintaining specificity >98%. We validated sensitivity in samples donated after self-reported swab-confirmed infections diagnoses. Sensitivity for first infections in unvaccinated donors was 98.1% (95% CI 98.0-98.2) and for infection after vaccination was 95.6% (95% CI 95.6-95.7) based on the standard cutoff. Regression analysis showed sensitivity was reduced in the Delta compared with Omicron period, in older donors, in asymptomatic infections, <30 days after infection, and for infection after vaccination. The standard Ortho N antibody threshold demonstrated good sensitivity, which was modestly improved with the revised cutoff.

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.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) mitigation measures in workplaces of employed US blood donors by industry and work arrangement. METHODS: During May-December 2021, blood donors responded to a survey; we describe the distribution of reported workplace mitigation measures by industry and work arrangement, organized using the hierarchy of controls. RESULTS: Of 53,433 respondents representing 21 industries, ventilation upgrades were reported by 4%-38% of respondents (overall: 20%); telework access ranged from 14%-80% (53% overall). Requiring masks (overall: 84%; range: 40%-94%), physical distancing (77%; 51%-86%), paid leave for illness (70%; 38%-87%), and encouraging vaccination (61%; 33%-80%) were common. Independent workers reported fewer mitigation measures than those in traditional employment settings. CONCLUSIONS: Mitigation measures varied by industry and work arrangement. Some mitigation measures may be challenging to implement or irrelevant in certain industries, supporting the idea that mitigation is not a one-size-fits-all strategy. POLICY IMPLICATIONS: Tailored strategies to mitigate workplace risks of disease transmission are vital. Strategies should rely on effective methods for identifying workplace controls (e.g., through the hierarchy of controls) and account for industry-specific characteristics and workplace environments.

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.

IMPORTANCE: Long-term symptoms, lasting more than 4 consecutive weeks after acute COVID-19 disease, are an important consequence of SARS-CoV-2 infection. Many prior studies have lacked a non-SARS-CoV-2-infected control population to distinguish background prevalence of symptoms from the direct impact of COVID-19 disease. OBJECTIVE: To examine the prevalence of long-term physical and mental health symptoms associated with SARS-CoV-2 infection in a large population of blood donors based on self-report and serologic test results. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included American Red Cross blood donors (aged ≥18 years) who were surveyed between February 22 and April 21, 2022, about new long-term symptoms arising after March 2020 and their SARS-CoV-2 infection status. All participants underwent at least 1 serologic test for antinucleocapsid antibodies between June 15, 2020, and December 31, 2021. EXPOSURES: SARS-CoV-2 infection as defined by a self-reported, confirmed acute infection or antinucleocapsid antibody positivity. MAIN OUTCOMES AND MEASURES: New long-term symptoms since March 2020, including 5 symptom categories (neurologic, gastrointestinal, respiratory and cardiac, mental health, and other). RESULTS: Among 818 361 individuals who received the survey, 272 965 (33.4%) responded, with 238 828 meeting the inclusion criteria (138 576 [58.0%] female; median [IQR] age, 59.0 [47.0-67.0] years). Of the 83 015 individuals with a history of SARS-CoV-2 infection, 43.3% reported new long-term symptoms compared with 22.1% of those without a history of SARS-CoV-2 infection. After controlling for age, sex, race and ethnicity, and number of underlying conditions, those with a history of SARS-CoV-2 infection had an increased odds of new long-term symptoms compared with those without (adjusted odds ratio [AOR], 2.55; 95% CI, 2.51-2.61). Female sex and a history of chronic conditions were associated with new long-term symptoms. Long-term symptoms in the other category (AOR, 4.14; 95% CI, 4.03-4.25), which included changes in taste or smell, and the respiratory and cardiac symptom categories (AOR, 3.21; 95% CI, 3.12-3.31) were most associated with prior SARS-CoV-2 infection. Mental health long-term symptoms were also associated with prior SARS-CoV-2 infection (AOR, 1.05; 95%, CI, 1.02-1.08). CONCLUSIONS AND RELEVANCE: This study's findings suggest that long-term symptoms lasting more than 4 weeks are common in the adult population, but there is a significantly higher prevalence among those with SARS-CoV-2 infection. Continued efforts to define and track long-term sequelae of SARS-CoV-2 using a control group without infection and serologic information to include those who had asymptomatic or unidentified infections are needed.

BACKGROUND: There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (SARS-CoV-2 infection or COVID-19 vaccination). From a cohort of health care personnel, first responders, and other frontline workers in six US states, we examined heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. METHODS: Exposures included event-count (sum of infections and vaccine doses) and event-order, categorized into seven permutations of vaccination and/or infection. Outcome was level of serum binding antibodies against receptor binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding Ig), measured by enzyme-linked immunosorbent assay. Mean antibody levels were examined up to 365 days after each of the 1st-7th events. RESULTS: Analysis included 5,793 participants measured from August 7, 2020 to April 15, 2023. Hybrid immunity from infection before one or two vaccine doses elicited modestly superior antibody responses after the 2nd and 3rd events (compared to infections or vaccine-doses alone). This superiority was not evident after the 4th and 5th events (additional doses). Among adults infected before vaccination, adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (0.81-0.94), and 0.99 (0.85-1.15) after the 2nd-5th events, respectively. Post-vaccination infections elicited superior responses: adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were: 0.93 (0.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the 2nd-5th events, respectively. CONCLUSIONS AND RELEVANCE: Findings reflecting heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.

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.

INTRODUCTION: Cardiometabolic diseases are associated with greater COVID-19 severity; however, the influences of cardiometabolic health on SARS-CoV-2 infections after vaccination remain unclear. Our objective was to investigate the associations between temporal blood pressure and total cholesterol patterns and incident SARS-CoV-2 infections among those with serologic evidence of vaccination. METHODS: In this prospective cohort of blood donors, blood samples were collected in 2020-2021 and assayed for binding antibodies of SARS-CoV-2 nucleocapsid protein antibody seropositivity. We categorized participants into intraindividual pattern subgroups of blood pressure and total cholesterol (persistently, intermittently, or not elevated [systolic blood pressure <130 mmHg, diastolic blood pressure <80 mmHg, total cholesterol <200 mg/dL]) across the study time points. RESULTS: Among 13,930 donors with 39,736 donations representing 1,127,071 person-days, there were 221 incident SARS-CoV-2 infections among those with serologic evidence of vaccination (1.6%). Intermittent hypertension was associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination risk (adjusted incidence rate ratio=2.07; 95% CI=1.44, 2.96; p<0.01) than among participants with consistent normotension on the basis of a multivariable Poisson regression. Among men, intermittently elevated total cholesterol (adjusted incidence rate ratio=1.90; 95% CI=1.32, 2.74; p<0.01) and higher BMI at baseline (adjusted hazard ratio=1.44; 95% CI=1.07, 1.93; p=0.01; per 10 units) were associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination probability; these associations were null among women (both p>0.05). CONCLUSIONS: Our findings underscore that the benefits of cardiometabolic health, particularly blood pressure, include a lower risk of SARS-CoV-2 infection after vaccination.

The COVID-19 pandemic underlined the importance of serosurveillance as an evidence-based tool to understand population immunity, track viral transmission, and guide public health decision making.1 Since the start of the COVID-19 pandemic, more than 4200 seroprevalence studies have been done in over 145 countries by testing blood specimens from more than 34 million people.2 In early 2023, the Robert Koch Institute, Germany's national public health institute, convened an online symposium about international serological studies that involved research organisations, national public health agencies, institutes, and regional public health agencies from low-income and middle-income countries. The invited participants reflected on lessons learned and drew practical conclusions on challenges, opportunities, and next steps (the participating groups are listed in the appendix). Attendees had implemented seroprevalence studies at the national or regional level since the start of the COVID-19 pandemic, and collectively addressed the questions on how to use this investment to maximise continued public health benefits and to inform future pandemic preparedness and response. Here, we discuss the primary lessons identified by the meeting attendees.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in neonates, infants, and children worldwide. The virus is estimated to infect 97% of this population in the United States by the age of 2 years, leading to hospitalization for severe lower respiratory tract disease in 2-3% of infants younger than age 6 months. Two preventive options, prenatal administration of a maternal vaccine and administration of a long-acting monoclonal antibody to the infant, are now available for the prevention of RSV-associated lower respiratory tract infection in infants in the United States. The U.S. Food and Drug Administration (FDA) has approved and the Centers for Disease Control and Prevention (CDC) has recommended a new maternal vaccination, RSVPreF, to be administered between 32 0/7 and 36 6/7 weeks of gestation to reduce the risk of RSV-associated lower respiratory tract infection in infants in the first 6 months of life. The monoclonal antibody nirsevimab was approved by the FDA and recommended by the CDC for prevention of RSV-associated lower respiratory tract infection in infants younger than age 8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at high risk for RSV-associated lower respiratory tract infection and entering their second RSV season. Either maternal vaccination during pregnancy or monoclonal antibody administration to the infant is recommended to prevent RSV-associated lower respiratory tract infection among infants, but both are not needed for most infants. Given that the availability of these products may vary as these recommendations are implemented, it is important that obstetricians and other prenatal practitioners have the information they need to counsel their pregnant patients about both options. We review the safety and efficacy of these products, current recommendations for their use, and relative advantages and disadvantages of both newly approved options for the prevention of RSV-associated lower respiratory tract infection in infants to assist obstetricians and other prenatal practitioners in their counseling of pregnant patients.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. Nirsevimab (Bevfortus, Sanofi and AstraZeneca) is recommended to prevent RSV-associated lower respiratory tract infection (LRTI) in infants. In August 2023, the Food and Drug Administration (FDA) approved RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant persons as a single dose during 32-36 completed gestational weeks (i.e., 32 weeks and zero days' through 36 weeks and 6 days' gestation) to prevent RSV-associated lower respiratory tract disease in infants aged <6 months. Since October 2021, CDC's Advisory Committee on Immunization Practices (ACIP) RSV Vaccines Pediatric/Maternal Work Group has reviewed RSV epidemiology and evidence regarding safety, efficacy, and potential economic impact of pediatric and maternal RSV prevention products, including RSVpreF vaccine. On September 22, 2023, ACIP and CDC recommended RSVpreF vaccine using seasonal administration (i.e., during September through end of January in most of the continental United States) for pregnant persons as a one-time dose at 32-36 weeks' gestation for prevention of RSV-associated LRTI in infants aged <6 months. Either maternal RSVpreF vaccination during pregnancy or nirsevimab administration to the infant is recommended to prevent RSV-associated LRTI among infants, but both are not needed for most infants. All infants should be protected against RSV-associated LRTI through use of one of these products.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children. Since October 2021, the Advisory Committee on Immunization Practices (ACIP) Maternal and Pediatric RSV Work Group has reviewed evidence on the safety and efficacy of nirsevimab among infants and young children. On August 3, 2023, ACIP recommended nirsevimab for all infants aged <8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at increased risk for severe RSV disease and are entering their second RSV season. On the basis of pre-COVID-19 pandemic patterns, nirsevimab could be administered in most of the continental United States from October through the end of March. Nirsevimab can prevent severe RSV disease among infants and young children at increased risk for severe RSV disease.

Introduction The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time.Study Design/Methods During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time.Results/Findings For all regions, seroprevalence was &lt;1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC.Conclusion Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.Summary SARS-CoV-2 serosurveillance data from blood donors in 6 US regions were used to estimate population weighted seroprevalence. Seroprevelance rates were higher in case rates. The study was expanded to a national donor serosurveillance program.Disclaimer The content is solely the responsibility of the authors and does not represent the policy of the National Institutes of Health or the Department of Health and Human Services. Any specific brandnames included in this manuscript are for identification purposes only and are not intended to represent an endorsement by CDC. The findings and conclusions in this report are those of the authorsand do not necessarily represent the official position of the Centers of Disease Control and Prevention.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors were supported by research contracts from the National Heart, Lung, and Blood Institute (NHLBI Contracts HHSN 75N92019D00032 and HHSN 75N92019D00033) as well as with funding support from the National Institute of Allergies and Infectious Diseases (NIAID), NIH.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:The study was reviewed by the UCSF Committee for Human Research and determined to meet the definition of research as defined in 46.102(l) but did not involve human subjects based on anonymization of data and routine consent for blood donation testing that includes use of residual samples for research purposes (as defined in 46.103(e)(1) consistent with applicable federal law and CDC policy (45 C.F.R. part 46; 21 C.F.R. part 56; 42 U.S.C. p241(d), 5 U.S.C. p552a, 44 U.S.C. p3501)).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 pros ective 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.YesThe data is not being made publicly available for privacy reasons related to federal regulations but a limited dataset may be made available upon request after formal review by NHLBI and CDC's privacy office before release.

SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by research contracts from the Centers for Disease Control and Prevention (CDC Contract 75D30120C08170).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:All blood donors consented to use of de-identified, residual specimens for further research purposes. UCSF IRB provided explicit approval for VRI self-certification that use of the de-identified CCP donations in this study does not meet the criteria for human subjects research. CDC investigators reviewed and relied on this determination as consistent with applicable federal law and CDC policy (45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501).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.YesThe analytic data set is available upon request.

Law Enforcement Officers (LEOs), firefighters, and other first responders are at increased risk of SARS-CoV-2 infection compared to healthcare personnel but have relatively low COVID-19 vaccine uptake. Resistance to COVID-19 vaccine mandates among first responders has the potential to disrupt essential public services and threaten public health and safety. Using data from the HEROES-RECOVER prospective cohorts, we report on the increased illness burden of COVID-19 among unvaccinated first responders. From January to September 2021, first responders contributed to weekly active surveillance for COVID-19-like illness (CLI). Self-collected respiratory specimens collected weekly, irrespective of symptoms, and at the onset CLI were tested by Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay for SARSCoV-2. Among 1415 first responders, 17% were LEOs, 68% firefighters, and 15% had other first responder occupations. Unvaccinated (41%) compared to fully vaccinated (59%) first responders were less likely to believe COVID-19 vaccines are very or extremely effective (17% versus 54%) or very or extremely safe (15% versus 54%). From January through September 2021, among unvaccinated LEOs, the incidence of COVID-19 was 11.9 per 1,000 person-weeks (95%CI=7.0-20.1) compared to only 0.6 (95%CI=0.2-2.5) among vaccinated LEOs. Incidence of COVID-19 was also higher among unvaccinated firefighters (9.0 per 1,000 person-weeks; 95%CI=6.4-12.7) compared to those vaccinated (1.8 per 1,000; 95%CI=1.1-2.8). Once they had laboratory-confirmed COVID-19, unvaccinated first responders were sick for a mean+/-SD of 14.7+/-21.7 days and missed a mean of 38.0+/-46.0 hours of work. These findings suggest that state and local governments with large numbers of unvaccinated first responders may face major disruptions in their workforce due to COVID-19 illness. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. METHODS: In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. RESULTS: The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. CONCLUSIONS: Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.

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.

Although reinfections with SARS-CoV-2 have occurred in the United States with increasing frequency, U.S. epidemiologic trends in reinfections and associated severe outcomes have not been characterized. Weekly counts of SARS-CoV-2 reinfections, total infections, and associated hospitalizations and deaths reported by 18 U.S. jurisdictions during September 5, 2021-December 31, 2022, were analyzed overall, by age group, and by five periods of SARS-CoV-2 variant predominance (Delta and Omicron [BA.1, BA.2, BA.4/BA.5, and BQ.1/BQ.1.1]). Among reported reinfections, weekly trends in the median intervals between infections and frequencies of predominant variants during previous infections were calculated. As a percentage of all infections, reinfections increased substantially from the Delta (2.7%) to the Omicron BQ.1/BQ.1.1 (28.8%) periods; during the same periods, increases in the percentages of reinfections among COVID-19-associated hospitalizations (from 1.9% [Delta] to 17.0% [Omicron BQ.1/BQ.1.1]) and deaths (from 1.2% [Delta] to 12.3% [Omicron BQ.1/BQ.1.1]) were also substantial. Percentages of all COVID-19 cases, hospitalizations, and deaths that were reinfections were consistently higher across variant periods among adults aged 18-49 years compared with those among adults aged ≥50 years. The median interval between infections ranged from 269 to 411 days by week, with a steep decline at the start of the BA.4/BA.5 period, when >50% of reinfections occurred among persons previously infected during the Alpha variant period or later. To prevent severe COVID-19 outcomes, including those following reinfection, CDC recommends staying up to date with COVID-19 vaccination and receiving timely antiviral treatments, when eligible.