Effects of COVID-19 vaccination and previous SARS-CoV-2 infection on omicron infection and severe outcomes in children under 12 years of age in the USA: an observational cohort study.

BACKGROUND: Data on the protection conferred by COVID-19 vaccination and previous SARS-CoV-2 infection against omicron (B.1.1.529) infection in young children are scarce. We aimed to estimate the time-varying effects of primary and booster COVID-19 vaccination and previous SARS-CoV-2 infection on subsequent omicron infection and severe illness (hospital admission or death) in children younger than 12 years of age. METHODS: In this observational cohort study, we obtained individual-level records on vaccination with the BNT162b2 and mRNA-1273 vaccines and clinical outcomes from the North Carolina COVID-19 Surveillance System and the COVID-19 Vaccine Management System for 1 368 721 North Carolina residents aged 11 years or younger from Oct 29, 2021 (Oct 29, 2021 for children aged 5-11 years and June 17, 2022 for children aged 0-4 years), to Jan 6, 2023. We used Cox regression to estimate the time-varying effects of primary and booster vaccination and previous infection on the risks of omicron infection, hospital admission, and death. FINDINGS: For children 5-11 years of age, the effectiveness of primary vaccination against infection, compared with being unvaccinated, was 59·9% (95% CI 58·5-61·2) at 1 month, 33·7% (32·6-34·8) at 4 months, and 14·9% (95% CI 12·3-17·5) at 10 months after the first dose. Compared with primary vaccination only, the effectiveness of a monovalent booster dose after 1 month was 24·4% (14·4-33·2) and that of a bivalent booster dose was 76·7% (45·7-90·0). The effectiveness of omicron infection against reinfection was 79·9% (78·8-80·9) after 3 months and 53·9% (52·3-55·5) after 6 months. For children 0-4 years of age, the effectiveness of primary vaccination against infection, compared with being unvaccinated, was 63·8% (57·0-69·5) at 2 months and 58·1% (48·3-66·1) at 5 months after the first dose, and the effectiveness of omicron infection against reinfection was 77·3% (75·9-78·6) after 3 months and 64·7% (63·3-66·1) after 6 months. For both age groups, vaccination and previous infection had better effectiveness against severe illness as measured by hospital admission or death as a composite endpoint than against infection. INTERPRETATION: The BNT162b2 and mRNA-1273 vaccines were effective against omicron infection and severe outcomes in children younger than 12 years, although the effectiveness decreased over time. Bivalent boosters were more effective than monovalent boosters. Immunity acquired via omicron infection was high and waned gradually over time. These findings can be used to develop effective prevention strategies against COVID-19 in children younger than 12 years. FUNDING: US National Institutes of Health.

Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes.

Importance: Data about the association of COVID-19 vaccination and prior SARS-CoV-2 infection with risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies. Objective: To estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death. Design, Setting, and Participants: Cohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022. Exposures: COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection. Main Outcomes and Measures: Rate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19-related hospitalization and death. Results: The median age among the 10.6 million participants was 39 years; 51.3% were female, 71.5% were White, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated. There were 2 771 364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with being unvaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.51-0.53) for mRNA-1273, and 0.51 (95% CI, 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for mRNA-1273, and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.19-0.31) for Ad26.COV2.S. For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had the adjusted RR relative to primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had the adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had the adjusted RR of 0.84 (95% CI, 0.82-0.86) and boosting with mRNA-1273 had the adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months. Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated at 0.23 (95% CI, 0.22-0.24) against infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death after 4 months. Conclusions and Relevance: Receipt of primary COVID-19 vaccine series compared with being unvaccinated, receipt of boosters compared with primary vaccination, and prior infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection (including Omicron) and resulting hospitalization and death. The associated protection waned over time, especially against infection.

Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina.

BACKGROUND: The duration of protection afforded by coronavirus disease 2019 (Covid-19) vaccines in the United States is unclear. Whether the increase in postvaccination infections during the summer of 2021 was caused by declining immunity over time, the emergence of the B.1.617.2 (delta) variant, or both is unknown. METHODS: We extracted data regarding Covid-19-related vaccination and outcomes during a 9-month period (December 11, 2020, to September 8, 2021) for approximately 10.6 million North Carolina residents by linking data from the North Carolina Covid-19 Surveillance System and the Covid-19 Vaccine Management System. We used a Cox regression model to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines in reducing the current risks of Covid-19, hospitalization, and death, as a function of time elapsed since vaccination. RESULTS: For the two-dose regimens of messenger RNA (mRNA) vaccines BNT162b2 (30 µg per dose) and mRNA-1273 (100 µg per dose), vaccine effectiveness against Covid-19 was 94.5% (95% confidence interval [CI], 94.1 to 94.9) and 95.9% (95% CI, 95.5 to 96.2), respectively, at 2 months after the first dose and decreased to 66.6% (95% CI, 65.2 to 67.8) and 80.3% (95% CI, 79.3 to 81.2), respectively, at 7 months. Among early recipients of BNT162b2 and mRNA-1273, effectiveness decreased by approximately 15 and 10 percentage points, respectively, from mid-June to mid-July, when the delta variant became dominant. For the one-dose regimen of Ad26.COV2.S (5 × 1010 viral particles), effectiveness against Covid-19 was 74.8% (95% CI, 72.5 to 76.9) at 1 month and decreased to 59.4% (95% CI, 57.2 to 61.5) at 5 months. All three vaccines maintained better effectiveness in preventing hospitalization and death than in preventing infection over time, although the two mRNA vaccines provided higher levels of protection than Ad26.COV2.S. CONCLUSIONS: All three Covid-19 vaccines had durable effectiveness in reducing the risks of hospitalization and death. Waning protection against infection over time was due to both declining immunity and the emergence of the delta variant. (Funded by a Dennis Gillings Distinguished Professorship and the National Institutes of Health.).

The incidence of human papillomavirus infection following treatment for cervical neoplasia: a systematic review.

OBJECTIVE: To systematically review the published literature in order to estimate the incidence and describe the variability of human papillomavirus (HPV) infection in women following treatment for cervical neoplasia. METHODS: Several scientific literature databases (e.g. PubMed, ISI Web of Science) were searched through January 31, 2012. Eligible articles provided data on (i) baseline HPV infection status within 6 months prior to or at time of treatment (pre-treatment); and (ii) HPV test results for women's first visit after treatment occurring within 36 months (post-treatment). We abstracted and summarized the post-treatment incidence of newly detected HPV genotypes that were not present at pre-treatment, overall and stratified by study and other population characteristics. RESULTS: A total of 25 studies were included, reporting post-treatment HPV incidence in nearly 2000 women. Mean patient age ranged from 31 to 43 years (median 36). Most studies used cervical exfoliated cell specimens to test for HPV DNA (n=20; 80%), using polymerase chain reaction (n=21; 84%). Cervical neoplasia treatment included loop electrical excision procedure (n=11; 44%); laser conization (n=2; 8%); laser ablation, surgical conization, cryotherapy, alpha-interferon (n=1; 4% each); or multiple treatment regimens (n=8; 32%). Follow-up times post-treatment ranged from 1.5 to 36 months (median 6). More than half of studies (n=17; 68%) estimated the incidence of any HPV type following treatment, while 7 (28%) focused specifically on high-risk (HR) HPV. HPV incidence after treatment varied widely, ranging from 0 to 47% (interquartile range: 0%-15%) in up to 3 years of follow-up after treatment. Lower HPV incidence was observed among studies that included relatively younger women, used laser conization, focused on HR-HPV rather than overall HPV infection, and had a lower proportion of recurrent cervical disease. CONCLUSIONS: These modest summary incidence estimates from the published literature can guide clinicians, epidemiologists and health economists in developing best practices for post-treatment cervical cancer prevention.