Objectives: It is unclear whether agricultural workers working during epidemics frequently introduce respiratory infections into their homes and trigger secondary transmission. We evaluate secondary attack rates (SAR) and transmission risk in households of agricultural workers in Guatemala during the COVID-19 pandemic. Methods: Households of participants in a workplace surveillance cohort were enrolled from September 2021 to August 2023. All participants reported symptoms twice weekly and provided saliva weekly for SARS-CoV-2 reverse-transcriptase-polymerase chain reaction testing. Upon SARS-CoV-2 detection, participants submitted saliva three times per week for 4 weeks. We calculated SARs, and we estimated the risk of transmission to household contacts adjusting for demographic factors, COVID-19 vaccination status, seropositivity, and significant covariates (p ≤ 0.05) in univariable analyses. Results: Among 83 households with 376 individuals, 48 (58%) had at least one SARS-CoV-2 infection (120 SARS-CoV-2 infections, 0.6 per 100 person-weeks), resulting in 64 secondary (SAR = 0.35, 95% confidence interval [CI] 0.28-0.43) and eight tertiary infections (tertiary attack rate = 0.07, 95% CI 0.03-0.13). The risk of secondary transmission increased by 112% among household contacts whose index cases were positive for ≥11 days (risk ratio: 2.12, 95% CI 1.29-3.49) but did not increase for those whose index case was positive for 6-10 days (risk ratio: 1.40, 95% CI 0.77-2.57) compared to those with index cases positive for ≤5 days. Conclusions: More than half of agricultural households became infected with SARS-CoV-2 and approximately two-thirds of these had secondary chains of transmission, especially when index cases shed SARS-CoV-2 longer. © 2025 The Authors

Few type-specific antibodies that recognize drifted epitopes are made during post-vaccination exposures to SARS-CoV-2 variants(1-12), perhaps due to suppression by previous immunity. We compared type-specific B cell responses in unvaccinated and vaccinated individuals with Delta and Omicron BA.1 SARS-CoV-2 variant infections. For both Delta, which is antigenically similar to the vaccine strain, and the more distant BA.1 variant, neutralizing antibodies were greater in post-vaccination variant infections than in primary variant infections. Delta type-specific memory B cells were reduced in post-vaccination Delta infections relative to primary variant infections. Yet some drifted epitopes in the Delta variant elicited minimal responses even in primary infections. For BA.1 infections, type-specific antibodies and memory B cells were mostly undetectable, irrespective of previous immunity. Thus, poor intrinsic antigenicity of drifted epitopes in Delta and BA.1 infections superseded the impact of previous immunity. Enhancing the immunogenicity of vaccine antigens may promote type-specific responses.

BACKGROUND: To better establish the value of vaccination against influenza viruses, we estimated vaccine-averted influenza illnesses among young children and older adults in Chile, Guyana, and Paraguay. METHODS: We gathered country- and target population-specific data on monthly influenza hospitalizations, vaccine coverage, and vaccine effectiveness from surveillance records and immunization registries during 2013-2018. We applied a static compartmental model to estimate differences in the number influenza-associated respiratory disease events (symptomatic nonhospitalized illnesses, medically attended illnesses, hospitalizations) in the presence and absence of influenza vaccination programs. RESULTS: Between 2013 and 2018, vaccinating 68% of children aged 6-23 months in Chile averted an annual mean of 14 617 nonhospitalized, 9426 medically attended, and 328 hospitalized influenza illnesses; vaccinating 28% of children aged 6-23 months in Paraguay averted 1115 nonhospitalized, 719 medically attended, and 25 hospitalized influenza illnesses. Vaccinating 59% of older adults in Chile averted an annual mean of 83 429 nonhospitalized, 37 079 medically attended, and 1390 hospitalized influenza illnesses; vaccinating 36% of older adults in Paraguay averted an annual mean of 3932 nonhospitalized, 1748 medically attended, and 66 hospitalized influenza illnesses. In Guyana, a hypothetical campaign vaccinating 30% of children aged <5 years could have prevented an annual 1496 nonhospitalized, 971 medically attended, and 10 hospitalized influenza illnesses. Vaccinating 30% of adults aged ≥65 years could have prevented 568 nonhospitalized, 257 medically attended, and 10 hospitalized influenza illnesses. CONCLUSIONS: Influenza vaccination averted tens of thousands of illnesses and thousands of hospitalizations in Chile and Paraguay; influenza vaccination could have had a proportional benefit in Guyana.

BACKGROUND: In 2020, countries implemented universal surveillance to detect and monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. Although crucial for early monitoring efforts, universal surveillance is resource intensive. To understand the implications of transitioning from universal to sentinel surveillance for monitoring SARS-CoV-2 transmissibility, morbidity and mortality, and disease seriousness, we compared measures of SARS-CoV-2 reported from both surveillance strategies in Argentina, Chile, and Mexico. METHODS: We obtained weekly case counts in Argentina, Chile, and Mexico, in periods when both universal and sentinel surveillance were ongoing. To assess the countries' surveillance strategies, we measured the proportion of total sites that were included in sentinel surveillance. We compared 8 measures of SARS-CoV-2 transmissibility, morbidity and mortality, and disease seriousness between sentinel and universal surveillance and assessed the correlation between the 2 strategies for the 8 measures. Pearson and Spearman correlation was classified as very strong (rs = 0.8-1.0), strong (rs = 0.60-0.79), moderate (rs = 0.50-0.59), or poor (r < 0.50). RESULTS: The proportion of total sites included in sentinel surveillance was 5.8% for Argentina, 1.1% for Chile, and 7.6% for Mexico. A total of 21 measures were calculated (8 for Mexico, 8 for Chile, and 5 for Argentina). Of these, 17 showed consistency between the 2 surveillance strategies, with strong or very strong correlations (r = 0.66-0.99): all 8 measures for Mexico, 6 of 8 measures for Chile, and 3 of 5 measures for Argentina. Each country had ≥1 measure reflecting transmissibility and ≥1 reflecting morbidity and mortality for which the correlation was strong or very strong. Chile and Mexico also had ≥1 measure of disease seriousness for which the correlation was strong. CONCLUSIONS: Our findings suggest that the integration of SARS-CoV-2 into national sentinel surveillance can yield information comparable to that provided by nationwide universal surveillance for measures related to SARS-CoV-2 transmissibility, morbidity and mortality, and seriousness of disease.

BACKGROUND: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance. METHODS: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was messenger RNA (mRNA) COVID-19 vaccination (2 or 3 monovalent doses). Odds of PCCs among vaccinated and unvaccinated persons were compared with logistic regression. RESULTS: Of 936 participants, 23.6% reported PCCs and 83.2% were vaccinated. Participants who received 3 vaccine doses had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (adjusted odds ratio [95% confidence interval]: 0.37 [.16-.85], 0.56 [.32-.97], and 0.48 [.25-.91], respectively). CONCLUSIONS: COVID-19 vaccination protected against development of PCCs among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important PCCs prevention tool.

Background: Annual estimates of seasonal influenza vaccine effectiveness can guide global risk communication and vaccination strategies to mitigate influenza-associated illness. We aimed to evaluate vaccine effectiveness in countries using the 2023 southern hemisphere influenza vaccine formulation.

The extent to which semi-quantitative antibody levels confer protection against SARS-CoV-2 infection in populations with heterogenous immune histories is unclear. Two nested case-control studies were designed within the multisite HEROES/RECOVER prospective cohort of frontline workers to study the relationship between antibody levels and protection against first-time post-vaccination infection and reinfection with SARS-CoV-2 from December 2021 to January 2023. All participants submitted weekly nasal swabs for rRT-PCR testing and blood samples quarterly and following infection or vaccination. Cases of first-time post-vaccination infection following a third dose of monovalent (origin strain WA-1) mRNA vaccine (n = 613) and reinfection (n = 350) were 1:1 matched to controls based on timing of blood draw and other potential confounders. Conditional logistic regression models were fit to estimate infection risk reductions associated with 3-fold increases in end titers for receptor binding domain (RBD). In first-time post-vaccination and reinfection study samples, most were female (67%, 57%), non-Hispanic (82%, 68%), and without chronic conditions (65%, 65%). The odds of first-time post-vaccination infection were reduced by 21% (aOR = 0.79, 95% CI = [0.66-0.96]) for each 3-fold increase in RBD end titers. The odds of reinfection associated with a 3-fold increase in RBD end titers were reduced by 23% (aOR = 0.77, 95% CI = [0.65-0.92] for unvaccinated individuals and 58% (aOR = 0.42, 95% CI = [0.22-0.84]) for individuals with three mRNA vaccine doses following their first infection. Frontline workers with higher antibody levels following a third dose of mRNA COVID-19 vaccine were at reduced risk of SARS-CoV-2 during Omicron predominance. Among those with previous infections, the point estimates of risk reduction associated with antibody levels was greater for those with three vaccine doses compared to those who were unvaccinated.

Background: Vaccination is one of the most effective measures to prevent influenza illness and its complications. Since the 1980s, countries and territories in the Americas have progressively implemented influenza vaccination operations in high-risk priority groups—such as older adults, pregnant persons, persons with comorbidities and health workers. Methods: In this review, we present the history and progress of the seasonal influenza program in the Americas, how the program contributed to the efficient and timely roll-out of the COVID-19 vaccines during the pandemic, and how the program can be used to promote immunization operations across the life span for existing and future vaccines. Results: The influenza A(H1N1)pdm09 pandemic in 2009 and the COVID-19 pandemic in 2020–2023 underscored the importance of having a robust seasonal influenza vaccination program for pandemic preparedness and response. Overall, countries with existing seasonal influenza vaccination programs were better prepared and rolled out the delivery of COVID-19 vaccines more quickly and effectively compared to other countries where the influenza vaccination platform was weak or non-existent. Conclusions: Traditionally, national immunization programs of developing countries have been predominately focused on newborns, children younger than five years and school-aged children while often limiting their investment in effective adult vaccination programs; these programs are typically isolated to high-income countries. Countries in Latin America have been the exception, with strong influenza vaccination programs for adults regardless of national income level. The presence of functional and effective adult influenza vaccination programs can also facilitate the acceptance and uptake of other adult vaccines targeting priority groups at higher risk for severe illness or complications. © 2024 by the authors.

OBJECTIVES: Trivalent inactivated influenza vaccine effectiveness was low in a prospective cohort of healthcare personnel (HCP) in Israel from 2016 to 2019. We conducted a randomised immunogenicity trial of quadrivalent recombinant influenza vaccine (RIV4) and standard-dose inactivated influenza vaccine (IIV4) among frequently and infrequently vaccinated previous cohort participants. METHODS: From October 2019 to January 2020, we enrolled and randomly allocated HCP from two Israeli hospitals to receive IIV4 or RIV4. Hemagglutination inhibition (HAI) antibody titres against 2019-2020 vaccine reference influenza viruses were compared between vaccine groups using geometric mean titre (GMT) ratios from sera collected one-month post-vaccination and by frequency of vaccination in the past 5 years (>2 vs ≤2). RESULTS: Among 415 HCP, the GMT ratio comparing RIV4 to IIV4 was 2.0 (95% confidence interval [CI] 1.7-2.7) for A(H1N1)pdm09, 1.6 (95% CI: 1.3-1.9) for A(H3N2), 1.8 (95% CI: 1.4-2.2) for B(Yamagata), and 1.1 (95% CI: 0.9-1.4) for B(Victoria). Similarly, RIV4 elicited higher HAI titres than IIV4 against all 2019-2020 vaccine reference viruses except B(Victoria) among infrequently and frequently vaccinated HCP (lower bound of GMT ratio 95% CIs ≥1.0). CONCLUSION: RIV4 had improved immunogenicity for influenza vaccine strains among both infrequent and frequent vaccinees compared to standard-dose IIV4. CLINICAL TRIALS REGISTRATION: NCT04523324.

BACKGROUND: Previous estimates of vaccine effectiveness (VE) against asymptomatic influenza virus infection based on seroconversion have varied widely and may be biased. We estimated 2022-2023 influenza VE against illness and asymptomatic infection in a prospective cohort. METHODS: In the HEROES-RECOVER cohort, adults at increased occupational risk of influenza exposure across 7 US sites provided weekly symptom reports and nasal swabs for reverse transcription-polymerase chain reaction (RT-PCR) influenza testing. Laboratory-confirmed influenza virus infections were classified as symptomatic (≥1 symptom) or asymptomatic during the week of testing. Participants reported demographic information and vaccination through surveys; most sites verified vaccination through medical record and immunization registry review. Person-time was calculated as days from the site-specific influenza season start (September-October 2022) through date of infection, study withdrawal, or season end (May 2023). We compared influenza incidence among vaccinated versus unvaccinated participants overall, by symptom status, and by influenza A subtype, using Cox proportional hazards regression adjusted for site and occupation. We estimated VE as (1 - adjusted hazard ratio) × 100%. RESULTS: In total, 269 of 3785 (7.1%) participants had laboratory-confirmed influenza, including 263 (98%) influenza A virus infections and 201 (75%) symptomatic illnesses. Incidence of laboratory-confirmed influenza illness among vaccinated versus unvaccinated participants was 23.7 and 33.2 episodes per 100 000 person-days, respectively (VE: 38%; 95% CI: 15%-55%). Incidence of asymptomatic influenza virus infection was 8.0 versus 11.6 per 100 000 (VE: 13%; 95% CI: -47%, 49%). CONCLUSIONS: Vaccination reduced incidence of symptomatic but not asymptomatic influenza virus infection, suggesting that influenza vaccination attenuates progression from infection to illness.

To reduce influenza-associated morbidity and mortality, countries in South America recommend annual influenza vaccination for persons at high risk for severe influenza illness, including young children, persons with preexisting health conditions, and older adults. Interim estimates of influenza vaccine effectiveness (VE) from Southern Hemisphere countries can provide early information about the protective effects of vaccination and help guide Northern Hemisphere countries in advance of their season. Using data from a multicountry network, investigators estimated interim VE against influenza-associated severe acute respiratory illness (SARI) hospitalization using a test-negative case-control design. During March 13-July 19, 2024, Argentina, Brazil, Chile, Paraguay, and Uruguay identified 11,751 influenza-associated SARI cases; on average, 21.3% of patients were vaccinated against influenza, and the adjusted VE against hospitalization was 34.5%. The adjusted VE against the predominating subtype A(H3N2) was 36.5% and against A(H1N1)pdm09 was 37.1%. These interim VE estimates suggest that although the proportion of hospitalized patients who were vaccinated was modest, vaccination with the Southern Hemisphere influenza vaccine significantly lowered the risk for hospitalization. Northern Hemisphere countries should, therefore, anticipate the need for robust influenza vaccination campaigns and early antiviral treatment to achieve optimal protection against influenza-associated complications.

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.

INTRODUCTION: Despite a longstanding Israel Ministry of Health recommendation that all healthcare personnel (HCP) receive a seasonal influenza vaccine, vaccine uptake among HCP remains below the country's target of 60% coverage. To understand factors related to vaccine hesitancy, we used data from a prospective three-year (2016-2019) influenza vaccine effectiveness study among Israeli HCP to examine knowledge, attitudes, and practices (KAP) about influenza vaccination and their association with vaccine uptake. METHODS: At the start of each influenza season, all participating HCP completed a questionnaire that included questions about socio-demographic and occupational characteristics, health status, and KAP related to seasonal influenza vaccination. We extracted vaccination history from electronic medical records and employee vaccination registries. We used logistic regression models to identify demographic and occupational factors, and KAP about influenza vaccination, associated with receipt of vaccination. RESULT: A total of 2,126 HCP were enrolled and had available data on vaccination history. Their median age was 42 years [IQR 35-52], and 73 % self-identified as female. Influenza vaccine uptake in 2016, 2017 and 2018 was 46 %, 48 % and 47 %, respectively. Overall, 36 % of HCP had received an influenza vaccine in ≥ 4 of the eight years prior. HCP aged 35-49 years were less likely to receive influenza vaccine compared to HCP aged ≥ 50 years (OR: 0.81 [95 % CI: 0.67-0.98]). Nurses and allied personnel were less likely to receive influenza vaccine compared to physicians (OR: 0.63 [95 % CI: 0.50-0.78] and OR: 0.53 [95 % CI: 0.40-0.70], respectively). The emotional benefit of vaccination (e.g., anticipating regret if not vaccinated) and the perception of vaccine safety were factors associated with vaccine uptake (OR: 7.60 [95 % CI: 6.27-9.22] and OR: 3.43 [95 % CI:2.91-4.03], respectively). CONCLUSION: Among HCP at two hospitals in Israel, less than half received an annual influenza vaccine. Older HCP, physicians, and those who reported the emotional benefit of vaccination or agreed that influenza vaccines are safe were more likely to be vaccinated. Future influenza vaccination campaigns could focus on these demographic groups and tailor messages emphasizing the emotional benefits of vaccination and vaccine safety to increase seasonal influenza vaccine uptake among HCP in Israel.

BACKGROUND: Vaccine effectiveness (VE) is essential to monitor the performance of vaccines and generate strategic information to guide decision making. We pooled data from six Latin American countries to estimate the effectiveness of COVID-19 vaccines in preventing laboratory-confirmed SARS-CoV-2 hospitalisation during three different pandemic waves from February 2021 to September 2022. METHODS: We used a test-negative case-control design in hospitalised adults in Chile, Costa Rica, Ecuador, Guatemala, Paraguay, and Uruguay. We estimated adjusted VE by age group (18-64 and ≥65 years), vaccine type and product for primary series vaccination and booster vaccination and by time since last dose during the Omicron variant dominant period. We used mixed effects logistic regression models adjusting for sex, age, week of onset of symptom onset and pre-existing conditions with country fit as a random effect term. FINDINGS: We included 15,241 severe acute respiratory infection (SARI) patients in the analysis. Among adults 18-64 years, VE estimates for primary series vaccination during pre-Delta and Delta periods ranged by product from 66.5% to 95.1% and from 33.5% to 88.2% for older adults. During the Omicron period, VE estimates for primary series were lower and decreased by time since last vaccination, but VE increased to between 26.4% and 57.4% when a booster was administered. INTERPRETATION: mRNA and viral vector vaccines presented higher VE for both primary series and booster. While VE decreased over time, protection against severe COVID-19-associated hospitalisation increased when booster doses were administered. Vaccination with additional doses should be recommended, particularly for persons at increased risk of developing severe COVID-19. FUNDING: This work was supported by a grant from the U.S. Centers for Disease Control and Prevention (CDC) through cooperative agreements with the Pan American Health Organization/World Health Organization.

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.

OBJECTIVES: Pediatric COVID-19 vaccine hesitancy and uptake is not well understood. Among parents of a prospective cohort of children aged 6 months-17 years, we assessed COVID-19 vaccine knowledge, attitudes, and practices (KAP), and uptake over 15 months. METHODS: The PROTECT study collected sociodemographic characteristics of children at enrollment and COVID-19 vaccination data and parental KAPs quarterly. Univariable and multivariable logistic regression models were used to test the effect of KAPs on vaccine uptake; McNemar's test for paired samples was used to evaluate KAP change over time. RESULTS: A total of 2,837 children were enrolled, with more than half (61 %) vaccinated by October 2022. Positive parental beliefs about vaccine safety and effectiveness strongly predicted vaccine uptake among children aged 5-11 years (aOR 13.1, 95 % CI 8.5-20.4 and aOR 6.4, 95 % CI 4.3-9.6, respectively) and children aged 12+ years (aOR 7.0, 95 % CI 3.8-13.0 and aOR 8.9, 95 % CI 4.4-18.0). Compared to enrollment, at follow-up parents (of vaccinated and unvaccinated children) reported higher self-assessed vaccine knowledge, but more negative beliefs towards vaccine safety, effectiveness, and trust in government. Parents unlikely to vaccinate their children at enrollment reported more positive beliefs on vaccine knowledge, safety, and effectiveness at follow-up. CONCLUSION: The PROTECT cohort allows for an examination of factors driving vaccine uptake and how beliefs about COVID-19 and the COVID-19 vaccines change over time. Findings of the current analysis suggest that these beliefs change over time and policies aiming to increase vaccine uptake should focus on vaccine safety and effectiveness.

Characterisation of influenza viruses in the southern hemisphere can guide local response and provide insights to northern hemisphere jurisdictions about their upcoming influenza season.1,2 Here, we present the information on 2023 end of influenza season in the southern hemisphere about influenza lineages, incidence of medically attended, laboratory-confirmed influenza cases, and influenza vaccine effectiveness (VE) against the antigen from surveillance clinics and a hospital in San Juan de Lurigancho and San Martin de Porres, the two most populated districts of Peru. | | From Jan 1 to Sept 30, 2023, surveillance nurses sought individuals with COVID-19-like illness (CLI) of any age seeking care at outpatient sentinel sites between Monday and Saturday. CLI was defined as presenting with at least two of the following symptoms or signs—fever, chills, rigors, myalgia, headache, or sore throat for not more than 7 days from illness onset.3 On March 7, 2023, the nurses expanded their search to CLI cases hospitalised for not more than 72 h at Cayetano Heredia National Hospital. | | Nurses obtained written consent to survey and swab CLI cases. Enrolled participants provided information on pre-existing conditions and influenza vaccination status. Individuals targeted for vaccination by Peru and vaccinated between Jan and Sept 2022, more than 14 days before enrolment, were considered vaccinated (appendix p 1).

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

What is already known about this topic? | | Effectiveness of seasonal influenza vaccine varies by season and circulating virus type. | | What is added by this report? | | The 2023 Southern Hemisphere seasonal influenza vaccine reduced the risk for influenza-associated hospitalizations by 52%. Circulating influenza viruses were genetically similar to those targeted by the 2023–24 Northern Hemisphere influenza vaccine formulation. This vaccine might offer similar protection if these viruses predominate during the coming Northern Hemisphere influenza season. | | What are the implications for public health practice? | | Vaccination remains one of the most effective ways to protect against influenza-associated complications. In anticipation of Northern Hemisphere influenza virus circulation, CDC recommends that health authorities encourage U.S. health care providers to administer seasonal influenza vaccine to all eligible persons aged ≥6 months.

BACKGROUND: The PROTECT study is a longitudinal cohort study initiated in July 2021 with weekly testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 4 states: Arizona, Florida, exas, and Utah. This study aims to examine vaccine-elicited antibody response against postvaccination SARS-CoV-2 infections. METHODS: Children aged 5-11 years had serum collected 14-59 days after their second dose of monovalent Pfizer-BioNTech coronavirus disease 2019 messenger RNA vaccine. Vaccine-elicited antibodies were measured using the area under the curve (AUC) and end-point titer using enzyme-linked immunosorbent assay (receptor-binding domain [RBD] and S2) and surrogate neutralization assays against ancestral (WA1) and Omicron (BA.2). RESULTS: 79 vaccinated participants (33 [41.7%] female; median age, 8.8 years [standard deviation, 1.9 years]), 48 (60.8%) were from Tucson, Arizona; 64 (81.0%) were non-Hispanic white; 63 (80.8%) attended school in person; 68 (86.1%) did not have any chronic conditions; and 47 (59.5%) were infected after vaccination. Uninfected children had higher AUCs against WA1 (P = .009) and Omicron (P = .02). The geometric mean and surrogate neutralization titer above the limit of detection was 346.0 for WA1 and 39.7 for Omicron, an 8.7-fold decrease (P < .001). After adjustment of covariates in the WA1-specific model, we observed a 47% reduction in the odds of postvaccination infection for every standard deviation increase in RBD AUC (aOR, 0.53 [95% confidence interval, .29-.97) and a 69% reduction in the odds of infection for every 3-fold increase in RBD end titer (0.31 [.06-1.57]). CONCLUSIONS: Children with higher antibody levels experienced a lower incidence of postvaccination SARS-CoV-2 infection.

Background Data on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited.Methods From a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August, 2020 to March, 2021 for SARS-CoV-2 infection by Reverse Transcription- Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum- neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models.Results Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose- 2.Conclusions A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS- CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.Main Point Summary One dose of mRNA COVID-19 vaccine after previous SARS-CoV-2 infection produced the highest neutralizing antibody titers; among those without history of infection, two doses of mRNA vaccine produced the most robust response.Competing Interest StatementAllison Naleway receives research funding from Pfizer and Vir Biotechnology and Jennifer Kuntz receives research funding from Pfizer, Novartis, and Vir Biotechnology for unrelated studies. All other authors: No conflicts. Funding StatementThis work was supported by the Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases [contracts 75D30120R68013 to Marshfield Clinic Research Institute, 75D30120C08379 to the University of Arizona, and 75D30120C08150 to Abt Associates].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 study is governed by Centers for Disease Control and Prevention IRB review board and gave ethical approval for this work.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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.YesAll data produced in the pres nt work are contained in the manuscript

Background Influenza viruses pose significant disease burdens through annual seasonal outbreaks and unpredictable pandemics. Existing influenza surveillance programs have relied heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness–specific student absenteeism (a-ILI) in pre-kindergarten through grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.Methods Starting in September 2014, ORCHARDS combined automated reporting of daily absenteeism within 6 schools and home visits to school children with acute respiratory infections (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing, long-standing, and highly effective influenza surveillance program, based on MAI at 5 primary care clinics in the same geographical area.Results Over the first 5 years, a-ILI occurred on 6,634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of the 1,728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Influenza (p&lt;0.001) and adenovirus (P=0.004) were significantly associated with a-ILI.Conclusion ORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives.Competing Interest StatementDr. Jonathan Temte has received financial and material support from Quidel Corporation. Dr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests.Funding StatementDr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests. This study has been supported by CDC through the cooperative agreement # 5U01CK000542-02-00. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 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 components of this proposed study were reviewed and approved by the Human Subjects Committees of the Education Research IRB - Social and Behavioral Sciences IRB (initial approval on September 4, 2013) and the University of Wisconsin Health Sciences-IRB (initial approval on December 5, 2013, with additional approvals as the protocol expanded and modified). The study is in full compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), FERPA, and all other federally mandated human subjects regulations. The US Office of Management and Budget has approved all forms used in this study.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 s atement 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 datasets generated and/or analyzed during the current study are not publicly available because the study is ongoing, but may be available from the corresponding author on reasonable request.4k4-year-old pre-kindergartena-Iabsenteeism due to illnessa-ILIabsenteeism due to influenza-like illnessa-TOTall-cause absenteeismARIacute respiratory infectionCDCCenters for Disease Control and PreventionCoVcoefficient of variationFERPAFamily Educational Rights and Privacy ActFluinfluenzaFDAFood and Drug AdministrationHIPPAHealth Insurance Portability and Accountability ActILIinfluenza-like illnessITinformation technologyIRBinstitutional review boardMAImedically attended influenzaNPnasopharyngealORCHARDSOregon Child Absenteeism Due to Respiratory Disease StudyOSDOregon School DistrictOPoropharyngealPCRpolymerase chain reactionRIDTrapid influenza diagnostic testRedCapResearch Electronic Data CaptureRPPrespiratory pathogen panelR/Erhinovirus/enterovirusRPhuman RNAse PSISschool information systemW-IISPWisconsin Influenza Incidence Surveillance ProjectWIRWisconsin Immunization RegistryWSLHWisconsin State Laboratory of HygieneVTMviral transport medium

BACKGROUND Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions.METHODS Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020—April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription–polymerase-chain-reaction (RT-PCR). VE was calculated as 100%×(1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation.RESULTS SARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post-dose-1 to 13 days after dose-2) or fully (≥14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (&lt;14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%–97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants.CONCLUSIONS Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.Competing Interest StatementAllison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work. Kurt T. Hegmann serves at the Editor of the American College of Occupational and Environmental Medicine evidence-based practice guidelines. Matthew S. These reported grants and personal fees from Reed Group and the American College of Occupational and Environmental Medicine, outside the submitted work. Other authors have reported no conflicts of interest.Funding StatementFunding provided in whole or in part by federal funds from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention under contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Laboratory, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc.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 study was reviewed and approved by the University of Arizona IRB as the single IRB for this studyAll 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.YesSummary data will be available once all study objectives are met.

Introduction In a multi-center prospective cohort of essential workers, we assessed knowledge, attitudes, and practices (KAP) by vaccine intention, prior SARS-CoV-2 positivity, and occupation, and their impact on vaccine uptake over time.Methods Initiated in July 2020, HEROES-RECOVER cohort provided socio-demographics and COVID-19 vaccination data. Using follow-up two surveys approximately three months apart, COVID-19 vaccine KAP, intention, and receipt was collected; the first survey categorized participants as reluctant, reachable, or endorsers.Results A total of 4,803 participants were included in the analysis. Most (70%) were vaccine endorsers, 16% were reachable, and 14% were reluctant. By May 2021, 77% had received at least one vaccine dose. KAP responses strongly predicted vaccine uptake, particularly positive attitudes about safety (aOR=5.46, 95% CI: 1.4-20.8) and effectiveness (aOR=5.0, 95% CI: 1.3-19.1). Participants prior SARS-CoV-2 infection were 22% less likely to believe the COVID-19 vaccine was effective compared with uninfected participants (aOR 0.78, 95% CI: 0.64-0.96). This was even more pronounced in first responders compared with other occupations, with first responders 42% less likely to believe in COVID-19 vaccine effectiveness (aOR=0.58, 95% CI 0.40-0.84). KAP responses shifted positively, with reluctant and reachable participant scores modestly increasing in positive responses for perceived vaccine effectiveness (7% and 12%, respectively) on the second follow-up survey; 25% of initially reluctant participants received the COVID-19 vaccine.Discussion Our study demonstrates attitudes associated with COVID-19 vaccine uptake and a positive shift in attitudes over time. First responders, despite potential high exposure to SARS-CoV-2, and participants with a history of SARS-CoV-2 infection were more vaccine reluctant.Conclusions COVID-19 vaccine KAP responses predicted vaccine uptake and associated attitudes improved over time. Perceptions of the COVID-19 vaccine can shift over time. Targeting messages about the vaccine’s safety and effectiveness in reducing SARS-CoV-2 virus infection and illness severity may increase vaccine uptake for reluctant and reachable participants.Competing Interest StatementThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Allison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work.Funding StatementThis study was funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention (contracts 75D30120R68013 to Marshfield Clinic Research Institute, 75D30120C08379 to the University of Arizona, and 75D30120C08150 to Abt Associates).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:- Ethics committee/IRB of University of Arizona gave ethical approval for this work - Ethic committee/IRB of all RECOVER Abt sites (University of Utah, Baylor Scott &amp; White, University of Miami, St Luke's, and Kaiser Permanente) gave ethical approval for this work - Ethics committee/IRB of Centers for Disease Control and Prevention deferred to RECOVER Abt sites and University of Arizona for this workI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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 repo ted 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.YesAll data produced in the present study are available upon reasonable request to the authorsFDAU.S. Food and Drug AdministrationCDCCenters for Disease Control and PreventionEUAEmergency Use AuthorizationKAPKnowledge, attitudes, and practicesHEROESArizona Healthcare, Emergency Response and Other Essential Workers SurveillanceRECOVERStudy and Research on the Epidemiology of SARS-CoV-2 in Essential Response PersonnelH-RHEROES-RECOVERHCPHealth care personnelFWFrontline workersPPEPersonal protective equipment

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.

OBJECTIVE: To estimate the 2022 end-of-season influenza vaccine effectiveness (VE) against severe acute respiratory illness (SARI) hospitalization in Chile, Paraguay, and Uruguay. METHODS: We pooled surveillance data from SARI cases in 18 sentinel surveillance hospitals in Chile (n=9), Paraguay (n=2), and Uruguay (n=7) during March 16-November 30, 2022. VE was estimated using a test-negative design and logistic regression models adjusted for country, age, sex, presence of ≥1 comorbidity, and week of illness onset. VE estimates were stratified by influenza virus type and subtype (when available) and influenza vaccine target population, categorized as children, individuals with comorbidities, and older adults, defined per countries' national immunization policies. RESULTS: Among the 3,147 SARI cases, there were 382 (12.1%) influenza test-positive case-patients; 328 (85.9%) influenza case-patients were in Chile, 33 (8.6%) were in Paraguay, and 21 (5.5%) were in Uruguay. In all countries, the predominant subtype was influenza A(H3N2) (92.6% of influenza cases). Adjusted VE against any influenza-associated SARI hospitalization was 33.8% (95% CI: 15.3%, 48.2%); VE against influenza A(H3N2)-associated SARI hospitalization was 30.4% (95% CI: 10.1%, 46.0%). VE estimates were similar across target populations. CONCLUSION: During the 2022 influenza season, influenza vaccination reduced the odds of hospitalization among those vaccinated by one-third. Health officials should encourage influenza vaccination in accordance with national recommendations.

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.(†) Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.(§) In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

BACKGROUND: Three doses of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines produce robust antibody responses, but data are limited among individuals previously infected with SARS-CoV-2. From a cohort of health care personnel (75.5%), first responders (4.6%), and other frontline workers (19.8%) in 6 US states, we longitudinally assessed antibody waning after dose-2, and response to dose-3, according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every three months, after SARS-CoV-2 infection, and after each COVID-19 vaccine dose. Sera were tested for antibodies and reported quantitatively as area under the serial dilution curve (AUC). Changes in the AUC values over time were compared as fold-changes using a linear mixed model. RESULTS: Analysis included 388 participants who received dose-3 by November 2021. Three comparison groups: (1) vaccine only with no known prior SARS-CoV-2 infection (n = 224); (2) infection prior to dose-1 (n = 123); and (3) infection after dose 2 and before dose-3 (n = 41). The interval from dose 2 and dose 3 was approximately 8-months. After dose-3, antibody levels rose 2.5-fold (95%CI = 2.2-3.0) in group 2, and 2.9-fold (95%CI = 2.6-3.3) in group 1. Those infected within 90 days before dose-3 (and median 233 days (IQR = 213-246) after dose-2) did not increase significantly after dose-3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection < 3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. EXPOSURES: SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. MAIN OUTCOMES AND MEASURES: Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase-polymerase chain reaction testing along with viral viability. RESULTS: Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, -6.1 [95% CI, -11.8 to -0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/L; difference, -1.0 [95% CI, -1.7 to -0.2] for Delta and 2.8 vs 3.5 log10 copies/L, difference, -1.0 [95% CI, -1.7 to -0.3] for Omicron). CONCLUSIONS AND RELEVANCE: In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.