Effectiveness of COVID-19 vaccination during pregnancy by circulating viral variant.

BACKGROUND: SARS-CoV-2 infection in pregnancy can result in a spectrum of asymptomatic to critical COVID-19 outcomes, including hospitalization, admission to the intensive care unit, or death. OBJECTIVE: This study aimed to investigate the effectiveness of messenger RNA COVID-19 vaccination during pregnancy against both hospitalization and infection, stratified by different variant circulations and by time since the last vaccine dose. STUDY DESIGN: This was a retrospective cohort study among pregnant persons who were members of Kaiser Permanente Northern California and delivered between December 15, 2020, and September 30, 2022. Pregnant persons who received any vaccine dose before the pregnancy onset date were excluded. The primary outcome was hospitalization for COVID-19, and the secondary outcome was polymerase chain reaction-confirmed SARS-CoV-2 infection. Exposure was receipt of a messenger RNA vaccine during pregnancy. Poisson regression was used to estimate the risk ratio of hospitalization by comparing vaccinated pregnant persons with unvaccinated pregnant persons adjusted for sociodemographic factors and calendar time. Cox regression was used to estimate the hazard ratio of infection by comparing vaccinated pregnant persons with unvaccinated pregnant persons. Vaccine effectiveness was estimated as 1 minus the rate ratio or the hazard ratio multiplied by 100. Vaccine effectiveness was estimated overall and by variant periods (before Delta, Delta, Omicron, and subvariants). RESULTS: Of 57,688 pregnant persons, 16,153 (28%) received at least 1 dose of a messenger RNA COVID-19 vaccine during pregnancy; moreover, 4404 pregnant persons tested positive for SARS-CoV-2 infection, and 108 pregnant persons were hospitalized during pregnancy. Overall, 2-dose vaccine effectiveness against hospitalization was 91% within <150 days of vaccination and 48% >150 days after vaccination. The 2-dose vaccine effectiveness within <150 days after vaccination was 100% during the original virus strain and Delta variant periods of the virus; vaccine effectiveness was 51% during the Omicron period. Of the hospitalization cases, 97% of pregnant persons were unvaccinated. During hospitalization, none of the vaccinated pregnant persons required ventilation or were admitted to the intensive care unit. Moreover, 2-dose vaccine effectiveness against infection was 54% within <150 days after vaccination and 26% ≥150 days after vaccination. CONCLUSION: Messenger RNA COVID-19 vaccination during pregnancy was effective against hospitalization for COVID-19 and SARS-CoV-2 infection. COVID-19 was mild among pregnant persons who were vaccinated compared with those who were unvaccinated. Thus, all pregnant persons should be strongly encouraged to receive messenger RNA COVID-19 vaccines to prevent severe disease.

Individual and neighborhood factors associated with being unvaccinated against COVID-19 among pregnant persons.

We investigated whether unvaccinated pregnant persons cluster geographically and determined factors associated with being unvaccinated using spatial and multivariate logistic regression analyses. Pregnant persons with deliveries from December 15, 2020, through September 30, 2022, at Kaiser Permanente Northern California were included. Of the 85,852 pregnant persons in the study, 46.6% were unvaccinated before and during pregnancy. Spatial analysis identified 5 clusters with high prevalence of unvaccinated pregnant persons. Within these clusters, the proportion of unvaccinated varied from 53% to 62% versus 39% outside the clusters. In covariate-adjusted analyses, residence in a cluster increased the odds of being unvaccinated by 1.64 (95% confidence interval (CI): 1.59,1.69). The odds of being unvaccinated increased among those aged 16-24 years (odds ratio [OR] = 2.69, CI: 2.55, 2.83), aged 25-34 years (OR = 1.59, CI: 1.54, 1.64) compared with age ≥ 35 years, black race (OR = 1.45, CI:1.37, 1.54), and subsidized insurance (OR = 1.32, CI: 1.26, 1.38). The odds of being unvaccinated also increased for pregnant persons living in neighborhoods where the proportion of adults with high school education or less was greater than 20%. Geographic clustering of unvaccinated pregnant persons suggests a need for population-specific-interventions to increase vaccine coverage.

Maternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life.

We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,311 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of ≥2 doses of COVID-19 vaccine received during pregnancy was 84% (95% confidence interval [CI]: 66, 93), 62% (CI: 39, 77) and 56% (CI: 34,71) during months 0-2, 0-4 and 0- 6 of a child's life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 21% (CI: -21,48), 14% (CI: -9,32) and 13% (CI: -3,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.

Maternal SARS-CoV-2 Vaccination and Infant Protection Against SARS-CoV-2 During the First 6 Months of Life.

We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,288 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of maternal vaccination was 85% (95% confidence interval [CI]: 67, 93), 64% (CI: 43, 78) and 57% (CI: 36,71) during the first 2, 4 and 6 months of life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 22% (CI: -18,48), 14% (CI: -10,32) and 12% (CI: -4,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.

Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination.

BACKGROUND: Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population. METHODS: Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination. RESULTS: From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54). CONCLUSIONS: Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.

Identification and description of mumps cases in a non-outbreak setting and evaluation of the effectiveness of mumps-containing vaccines over time.

Mumps outbreaks among previously vaccinated young adults raise concerns regarding waning vaccine immunity. This study identified, described and assessed the changing incidence of mumps cases following mumps-containing vaccination (MMR/MMRV) in a non-mumps outbreak setting. Potential cases between 1996 and 2018 were identified by the international classification of disease codes or by mumps laboratory test orders among Kaiser Permanente Northern California members. Medical charts were reviewed to confirm diagnoses, timing relative to vaccination and clinical characteristics. Among 474 potential cases, 257 (54.2%) were confirmed after chart review. A third of the cases were <10 years old at diagnosis and 48% were over 25 years. Most cases (92.2%) had parotitis and 5% of males had orchitis. Mumps rates decreased from 8.5 to 1.8/1,000,000 person-years as time since the second MMR/MMRV dose increased from <2 years to ≥10 years. Similarly, rates decreased from 16.3 to 3/1,000,000 person-years after at least 1 dose of MMR/MMRV. Mumps rates were higher among children aged ≤10 years compared with older age groups. In conclusion, in the context of a non-outbreak setting, this study suggests that waning of vaccine immunity to mumps appeared to have minimal clinical impact.

Long term risk of developing type 1 diabetes after HPV vaccination in males and females.

INTRODUCTION: Despite minimal evidence, public concerns that the human papillomavirus (HPV) vaccine can cause autoimmune diseases (AD) persist. We evaluated whether HPV vaccine is associated with a long-term increased risk of diabetes mellitus type 1 (DM1). METHODS: This was a retrospective cohort study in which we identified all potential DM1 cases from Kaiser Permanente Northern California (KPNC) members who were between 11 and 26 years old any time after June 2006 through December 2015. We chart reviewed a random sample of 100 DM1 cases to confirm diagnosis and to develop a computer algorithm that reliably determined symptom onset date. Our DM1 Analysis Population comprised all individuals who met membership criteria and who were age and sex eligible to have received HPV vaccine. We adjusted for age, sex, race, Medicaid, and years of prior KPNC membership by stratification using a Cox multiplicative hazards model with a calendar timeline. RESULTS: Our DM1 analysis included 911,648 individuals. Of 2613 DM1 cases identified, 338 remained in the analysis after applying our algorithm, HPV vaccine eligibility and membership criteria. Over the 10 years of the study period, comparing vaccinated with unvaccinated persons, we did not find an increased risk of DM1 associated with HPV vaccine receipt (hazard ratio 1.21, 95% Confidence Interval 0.94, 1.57). CONCLUSIONS: We found no increased risk for development of DM1 following HPV vaccination. Our study provides reassurance that during the 10-year time period after HPV vaccine was introduced, there was no substantial increased risk for DM1 following HPV vaccination.

Asthma exacerbations among asthmatic children receiving live attenuated versus inactivated influenza vaccines.

OBJECTIVE: To investigate whether there is a difference in the risk of asthma exacerbations between children with pre-existing asthma who receive live attenuated influenza vaccine (LAIV) compared with inactivated influenza vaccine (IIV). MATERIAL AND METHODS: We identified IIV and LAIV immunizations occurring between July 1, 2007 and March 31, 2014 among Kaiser Permanente Northern California members aged 2 to <18years with a history of asthma, and subsequent asthma exacerbations seen in the inpatient or Emergency Department (ED) setting. We calculated the ratio of the odds (OR) of an exacerbation being in the risk interval (1-14days) versus the comparison interval (29-42days) following immunization, separately for LAIV and IIV, and then examined whether the OR differed between children receiving LAIV and those receiving IIV ("difference-in-differences"). RESULTS: Among 387,633 immunizations, 85% were IIV and 15% were LAIV. Children getting LAIV vs. IIV were less likely to have "current or recent, persistent" asthma (25% vs. 47%), and more likely to have "remote history" of asthma (47% vs. 25%). Among IIV-vaccinated asthmatic children, the OR of an inpatient/ED asthma exacerbation was 0.97 (95% CI: 0.82-1.15). Among LAIV-vaccinated asthmatic children the OR was 0.38 (95% CI: 0.17-0.90). In the difference-in-differences analysis, the odds of asthma exacerbation following LAIV were less than IIV (Ratio of ORs: 0.40, CI: 0.17-0.95, p value: 0.04). CONCLUSION: Among children ≥2years old with asthma, we found no increased risk of asthma exacerbation following LAIV or IIV, and a decreased risk following LAIV compared to IIV.

Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B vaccines among persons 15-59 years of age.

BACKGROUND: Associations between vaccinations, particularly hepatitis B, and onset of rheumatoid arthritis (RA) have been reported, but examined in few large-scale studies. METHOD: Onset of RA cases and dates of vaccination against hepatitis B, tetanus, and influenza were identified in a retrospective chart review of approximately 1 million Kaiser Permanente Northern California members ages 15-59 years from 1997 through 1999. In a cohort analysis, rates of new-onset RA were compared between vaccinated and unvaccinated within 90, 180, and 365 days. In a case-control analysis, rates of vaccination during exposure intervals (90, 180, 365, and 730 days) were compared between cases and controls using conditional logistic regression. RESULTS: 378 RA cases were included in the cohort analysis; 37 additional cases were included in the case-control analysis. In the cohort analysis the relative risks of RA onset within 90, 180, or 365 days of hepatitis B vaccination were not significant (R.R.=1.44, p=0.53; R.R.=1.67, p=0.22; R.R.=1.23, p=0.59 respectively). We found a possible association between RA and influenza vaccine in the previous 180 and 365 days in the cohort analysis (R.R=1.36, p=0.03; R.R.=1.34, p=0.01 respectively), but in the case-control analysis, cases were no more likely than controls to have received any of the three vaccines. CONCLUSIONS: In this large retrospective study we found no statistically significant association between exposure to hepatitis B vaccine and onset of RA. A possible association between RA and influenza vaccination in the cohort study was not borne out in the larger case-control analysis.