Influenza Vaccine Effectiveness Against Illness and Asymptomatic Infection in 2022-2023: A Prospective Cohort Study.

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.

Hybrid Immunity and SARS-CoV-2 Antibodies: Results of the HEROES-RECOVER Prospective Cohort Study.

BACKGROUND: There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (infection with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] or vaccination against coronavirus disease 2019 [COVID-19]). From a multi-site cohort of frontline workers, we examined the heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. METHODS: Exposures included event count and event order, categorized into 7 permutations. Outcome was level of serum antibodies against receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding immunoglobulin). Means were examined up to 365 days after each of the first to seventh events. RESULTS: Analysis included 5793 participants measured from 7 August 2020 to 15 April 2023. Hybrid immunity from infection before 1 or 2 vaccine doses elicited modestly superior antibody responses after the second and third events (compared with infections or vaccine doses alone). This superiority was not repeated after additional events. Among adults infected before vaccination, adjusted geometric mean ratios (95% confidence interval [CI]) of anti-RBD early response (versus vaccinated only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (.81-.94), and 0.99 (.85-1.15) after the second to fifth 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 (.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the second to fifth events, respectively. CONCLUSIONS: Evidence of heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.

Incidence of laboratory-confirmed influenza and RSV and associated presenteeism and absenteeism among healthcare personnel, Israel, influenza seasons 2016 to 2019.

BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95% CI: 5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95% CI: 0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95% CI: 17.8-42.5). Work during illness occurred in 92% (95% CI: 91-93) of ARI episodes, absence from work in 38% (95% CI: 36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.

Effectiveness of Bivalent mRNA COVID-19 Vaccines in Preventing SARS-CoV-2 Infection in Children and Adolescents Aged 5 to 17 Years.

Importance: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. Objective: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. Design, Setting, and Participants: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. Exposure: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. Main Outcome and Measures: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. Results: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. Conclusion and Relevance: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Testing and Detection During Peripartum Hospitalizations Among a Multicenter Cohort of Pregnant Persons: March 2020-February 2021.

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. RESULTS: Among 17 858 pregnant persons, 10 863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10 683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% confidence interval [CI]: 1.03-1.79; referent: White) (site 1), Hispanic or Latino ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [site 2]). CONCLUSIONS: Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections.

Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019-2020 Influenza Season.

BACKGROUND: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. METHODS: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. RESULTS: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. CONCLUSIONS: Peripartum respiratory infections may be underrecognized.

Incidence and Clinical Characteristics of and Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Pregnant Individuals in the United States.

BACKGROUND: Data about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant individuals are needed to inform infection-prevention guidance and counseling for this population. METHODS: We prospectively followed a cohort of pregnant individuals during August 2020-March 2021 at 3 US sites. The 3 primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly midturbinate nasal swabs for SARS-CoV-2 reverse transcription-polymerase chain reaction testing, completed weekly illness symptom questionnaires, and submitted additional swabs with coronavirus disease 2019 (COVID-19)-like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. RESULTS: Among 1098 pregnant individuals followed for a mean of 10 weeks, 9% (99/1098) had SARS-CoV-2 infections during the study. Population-weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1000 (95% confidence interval, 5.7-14.3) person-weeks for any infection, 5.7 per 1000 (1.7-9.7) for symptomatic infections, and 3.5 per 1000 (0-7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infections and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. Median symptom duration was 10 (interquartile range, 6-16) days. CONCLUSIONS: Pregnant individuals in this study had a 1% risk of SARS-CoV-2 infection per week, underscoring the importance of COVID-19 vaccination and other prevention measures during pregnancy while SARS-CoV-2 is circulating in the community.

Attitudes Toward COVID-19 Illness and COVID-19 Vaccination among Pregnant Women: A Cross-Sectional Multicenter Study during August-December 2020.

OBJECTIVE: The aim of the study was to evaluate pregnant women's attitudes toward COVID-19 illness and vaccination and identify factors associated with vaccine acceptability. STUDY DESIGN: This was a cross-sectional survey among pregnant women enrolled in a prospective COVID-19 cohort study in Salt Lake City, UT, Birmingham, AL, and New York, NY, from August 9 to December 10, 2020. Women were eligible if they were 18 to 50 years old and <28 weeks of gestation. Upon enrollment, women completed surveys regarding concerns about COVID-19 illness and likelihood of getting COVID-19 vaccine if one were available during pregnancy. Vaccine acceptability was defined as a response of "very likely" or "somewhat likely" on a 4-point Likert scale. Factors associated with vaccine acceptability were assessed with multivariable logistic regression. RESULTS: Of 939 pregnant women eligible for the main cohort study, 915 (97%) consented to participate. Among these 915 women, 39% self-identified as White, 23% Black, 33% Hispanic, and 4% Other. Sixty-two percent received an influenza vaccine last season. Seventy-two percent worried about getting sick with COVID-19. If they were to get sick, 92% worried about harm to their pregnancy and 80% about harm to themselves. Only 41% reported they would get a vaccine. Of women who were unlikely to get vaccinated, the most frequently cited concern was vaccine safety for their pregnancy (82%). Non-Hispanic Black and Hispanic women had lower odds of accepting a vaccine compared with non-Hispanic White women (adjusted odds ratios [aOR] 0.4, 95% CI 0.2-0.6 for both). Receipt of influenza vaccine during the previous season was associated with higher odds of vaccine acceptability (aOR 2.1, 95% CI 1.5-3.0). CONCLUSION: Although most pregnant women worried about COVID-19 illness, <50% were willing to get vaccinated during pregnancy. Racial and ethnic disparities in plans to accept COVID-19 vaccine highlight the need to prioritize strategies to address perceived barriers among groups at high risk for COVID-19. KEY POINTS: · Less than half of pregnant patients stated they would get a COVID-19 vaccine.. · Protecting their baby was the most common reason for acceptance and refusal of the COVID-19 vaccine.. · Patients of minority race/ethnicity and those without prior influenza vaccination were less likely to accept the COVID-19 vaccine..

Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol.

BACKGROUND: The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. METHODS: Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. DISCUSSION: SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. TRIAL REGISTRATION: NCT03331991 . Registered on November 6, 2017.

Knowledge, attitudes, and practices associated with influenza vaccine uptake among healthcare personnel in Israel during three influenza seasons, 2016-2019.

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.

Longitudinal parental perception of COVID-19 vaccines for children in a multi-site, cohort study.

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.

Randomized Immunogenicity Trial Comparing 2019-2020 Recombinant and Egg-Based Influenza Vaccines among Frequently Vaccinated Healthcare Personnel in Israel.

BACKGROUND: Trivalent inactivated influenza vaccine effectiveness was low in a prospective cohort of healthcare personnel (HCP) in Israel from 2016-2019. We conducted a randomized 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 titers against 2019-2020 vaccine reference influenza viruses were compared between vaccine groups using geometric mean titer (GMT) ratios from sera collected one-month post-vaccination and by frequency of vaccination in the past 5 years (>2 versus ≤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 titers 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). CONCLUSIONS: RIV4 had improved immunogenicity for influenza vaccine strains among both infrequent and frequent vaccinees compared to standard-dose IIV4.

Evaluating Immunologic and Illness Outcomes of SARS-CoV-2 Infection in Vaccinated and Unvaccinated Children Aged ≥ 5 Years, in a Multisite Longitudinal Cohort.

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.

Association between SARS-CoV-2 infections during pregnancy and preterm live birth.

We examined associations between mild or asymptomatic prenatal SARS-CoV-2 infection and preterm live birth in a prospective cohort study. During August 2020-October 2021, pregnant persons were followed with systematic surveillance for RT-PCR or serologically confirmed SARS-CoV-2 infection until pregnancy end. The association between prenatal SARS-CoV-2 infection and preterm birth was assessed using Cox proportional-hazards regression. Among 954 pregnant persons with a live birth, 185 (19%) had prenatal SARS-CoV-2 infection and 123 (13%) had preterm birth. The adjusted hazard ratio for the association between SARS-CoV-2 infection and preterm birth was 1.28 (95% confidence interval 0.82-1.99, p = 0.28), although results did not reach statistical significance.

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Background: Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. Methods: In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Results: Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Conclusions: Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

Incidence Rates of Medically Attended COVID-19 in Infants Less Than 6 Months of Age.

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age. METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test results. Medically attended COVID-19 episodes were defined by positive SARS-CoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated. RESULTS: Among 18,192 infants <6 months of age whose mothers received prenatal care within the 3 systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants under 1 month of age (2.0 per 1000 person-weeks) and 1 month (2.0 per 1000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy. CONCLUSIONS: Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants.

Humoral Immune Response to Messenger RNA Coronavirus Disease 2019 Vaccination Among Children Aged 5-11 Years in a Multisite Prospective Cohort Study, September 2021-September 2022.

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.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy.

Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Agreement Between Pregnant Individuals' Self-Report of Coronavirus Disease 2019 (COVID-19) Vaccination and Medical Record Documentation.

For public health research such as vaccine uptake or effectiveness assessments, self-reported coronavirus disease 2019 (COVID-19) vaccination status may be a more efficient measure than verifying vaccination status from medical records if agreement between sources is high. We assessed agreement between self-reported and medical record-documented COVID-19 vaccination status among pregnant individuals followed in a cohort during August 2020-October 2021. At end of pregnancy, participants completed questionnaires about COVID-19 vaccine receipt during pregnancy; staff verified vaccination status using medical records. Agreement was assessed between self-reported and medical record vaccination status using Cohen's kappa. There was high agreement between self-reported and medical record vaccination status (Kappa coefficient=0.94, 95% CI 0.91-0.98), suggesting that self-report may be acceptable for ascertaining COVID-19 vaccination status during pregnancy.