Incidence and Predictors of Breakthrough and Severe Breakthrough Infections of SARS-CoV-2 After Primary Series Vaccination in Adults: A Population-Based Survey of 22 575 Participants.

BACKGROUND: Breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization). METHODS: In total, 89 762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively. RESULTS: The incidence was 0.45 (95% confidence interval [CI], .38-.50) during pre-Delta, 2.80 (95% CI, 2.25-3.14) during Delta, and 11.2 (95% CI, 8.80-12.95) during Omicron, per 10 000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic white, OR = 1.243; 95% CI, 1.073-1.441), larger household size (OR = 1.251 [95% CI, 1.048-1.494] for 3-5 vs 1 and OR = 1.726 [95% CI, 1.317-2.262] for more than 5 vs 1 person), rural versus urban living (OR = 1.383; 95% CI, 1.122-1.704), receiving Pfizer or Johnson & Johnson versus Moderna, and multiple comorbidities. Of the 1700 breakthrough infections, 1665 reported on severity; 112 (6.73%) were severe. Higher body mass index, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs. CONCLUSIONS: Breakthrough infection was 4-25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.

Long-term immune response to SARS-CoV-2 infection and vaccination in children and adolescents.

BACKGROUND: This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents. METHODS: Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed. RESULTS: N antibody levels reached a median of 84.10 U/ml (IQR: 20.2, 157.7) cutoff index (COI) ~ 6 months post-infection and increased slightly to a median of 85.25 (IQR: 28.0, 143.0) COI at 12 months post-infection. Peak S antibody levels were reached at a median of 2500 U/mL ~6 months post-vaccination and remained for ~12 months (mean 11.6 months, SD 1.20). CONCLUSIONS: This analysis provides evidence of robust durability of nucleocapsid and spike antibodies in a large pediatric sample up to 12 months post-infection/vaccination. This information can inform pediatric SARS-CoV-2 vaccination schedules. IMPACT: This study provided evidence of robust durability of both nucleocapsid and spike antibodies in a large pediatric sample up to 12 months after infection. Little is known about the long-term durability of natural and vaccine-induced SARS-CoV-2 antibodies in the pediatric population. Here, we determined the durability of anti-SARS-CoV-2 spike (S-test) and nucleocapsid protein (N-test) in children/adolescents after SARS-CoV-2 infection and/or vaccination lasts at least up to 12 months. This information can inform future SARS-CoV-2 vaccination schedules in this age group.

SARS-CoV-2 Serostatus and COVID-19 Illness Characteristics by Variant Time Period in Non-Hospitalized Children and Adolescents.

OBJECTIVE: To describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample. DESIGN: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old. SETTING: State of Texas, USA. PARTICIPANTS: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOME(S) AND MEASURE(S): SARS-CoV-2 antibody status was assessed by the Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Self-reported antigen or PCR COVID-19 test results and symptom status were also collected. RESULTS: Over half (57.2%) of the sample (N = 3911) was antibody positive. Symptomatic infection increased over time from 47.09% during the pre-Delta variant time period, to 76.95% during Delta, to 84.73% during Omicron, and to 94.79% during the Omicron BA.2. Those who were not vaccinated were more likely (OR 1.71, 95% CI 1.47, 2.00) to be infected versus those fully vaccinated. CONCLUSIONS: Results show an increase in symptomatic COVID-19 infection among non-hospitalized children with each progressive variant over the past two years. Findings here support the public health guidance that eligible children should remain up to date with COVID-19 vaccinations.

Comparison of Persistent Symptoms Following SARS-CoV-2 Infection by Antibody Status in Nonhospitalized Children and Adolescents.

BACKGROUND: The prevalence of long-term symptoms of coronavirus disease 2019 (COVID-19) in nonhospitalized pediatric populations in the United States is not well described. The objective of this analysis was to examine the presence of persistent COVID symptoms in children by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status. METHODS: Data were collected between October 2020 and May 2022 from the Texas Coronavirus Antibody REsponse Survey, a statewide prospective population-based survey among 5-90 years old. Serostatus was assessed by the Roche Elecsys Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein. Self-reported antigen/polymerase chain reaction COVID-19 test results and persistent COVID symptom status/type/duration were collected simultaneously. Risk ratios for persistent COVID symptoms were calculated versus adults and by age group, antibody status, symptom presence/severity, variant, body mass index and vaccine status. RESULTS: A total of 82 (4.5% of the total sample [n = 1813], 8.0% pre-Delta, 3.4% Delta and beyond) participants reported persistent COVID symptoms (n = 27 [1.5%] 4-12 weeks, n = 58 [3.3%] >12 weeks). Compared with adults, all pediatric age groups had a lower risk for persistent COVID symptoms regardless of length of symptoms reported. Additional increased risk for persistent COVID symptoms >12 weeks included severe symptoms with initial infection, not being vaccinated and having unhealthy weight (body mass index ≥85th percentile for age and sex). CONCLUSIONS: These findings highlight the existence of nonhospitalized youth who may also experience persistent COVID symptoms. Children and adolescents are less likely to experience persistent COVID symptoms than adults and more likely to be symptomatic, experience severe symptoms and have unhealthy weight compared with children/adolescents without persistent COVID symptoms.