ABSTRACT
Introduction: Vaccine safety in pregnancy is always of paramount importance. Current evidence of COVID-19 vaccine safety in pregnancy has been reassuring with no association found with negative maternal and neonatal outcomes. However, very few safety studies are conducted on a national level and investigate dosage, timing of vaccination as well as vaccine manufacturer. To fill this knowledge gap, we conducted a population based COVID-19 vaccine safety evaluation in England, including timing of vaccination by trimester, dosage and vaccine manufacturer received in pregnancy. Method: A matched case control study nested in a retrospective cohort where adverse maternal and neonatal pregnancy outcomes were compared across several COVID-19 vaccine exposures using conditional multivariable logistic regression, adjusting for a range of demographic and health characteristics. Eligible participants were identified from the national maternity services dataset (MSDS) and records were linked to hospital admission, national COVID-19 vaccine and COVID-19 testing databases. Matching criteria differed by outcome but included participant's age and estimated week of conception. Results: 514,013 pregnant individuals aged between 18 and 50 years were identified during the study period (births from 16th of April 2021- 31st March 2022). Receiving at least one dose of COVID-19 vaccine during pregnancy conferred lower odds of giving birth to a baby who was low birthweight (aOR=0.86, 95% CI: 0.79 - 0.93), preterm (aOR=0.89, 95% CI: 0.85 - 0.92) or who had an Apgar score less than 7 at five mins of age (aOR=0.89, 95% CI: 0.80 - 0.98). There was no association between vaccination in pregnancy and stillbirth (aOR=0.90, 95% CI: 0.76 - 1.07), neonatal death (aOR=1.27, 95% CI: 0.91 - 1.77) perinatal death (aOR=0.98, 95% CI: 0.83 - 1.16), and maternal venous thromboembolism in pregnancy (aOR=0.82, 95% CI: 0.43 - 1.56). The odds of maternal admission to intensive care unit were lower in vaccinated pregnant women (aOR=0.85, 95% CI: 0.76 - 0.95). Conclusion: COVID-19 vaccines are safe to use in pregnancy and they confer protection against SARS-CoV-2 infection which can lead to adverse outcomes for both the mother and the infant. Our findings generated important information to communicate to pregnant women and health professionals to support COVID-19 maternal vaccination programmes.
Subject(s)
Perinatal Death , Venous Thromboembolism , Death , COVID-19 , StillbirthABSTRACT
The duration of immunity after first SARS-CoV-2 infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. Using a retrospective population-based matched observational study approach, we identified cases with a first PCR positive test between 01 March 2020 and 30 September 2020 and cases were matched by age, sex, upper tier local authority of residence and testing route to individuals testing negative in the same week (controls) by PCR. After a 90-day pre-follow up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. There were 517,870 individuals in the matched cohort with 2,815 reinfection cases and 12,098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (OR 0.22, 0.21-0.23). Protection rose to 82% (OR 0.18, 0.17-0.19) after a sensitivity analysis excluded 934 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20-0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42-0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the Alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.
Subject(s)
COVID-19ABSTRACT
Background There are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended [≥]12-week interval between doses. Methods SARS-CoV-2 infection-naive and previously-infected adults receiving ChAd-BNT (ChAdOx1 nCoV-19, AstraZeneca followed by BNT162b2, Pfizer-BioNTech) or BNT-ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti-SARS-CoV-2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd-ChAd or BNT-BNT. Results During March-October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously-uninfected adults, S-antibody GMC at 30 days post-second dose were lowest for ChAd-ChAd (862 (95%CI, 694- 1069)) and significantly higher for ChAd-BNT (6233 (5522- 7035); GMR 6.29; (5.04- 7.85); p<0.001), BNT-ChAd (4776 (4066- 5610); GMR 4.55 (3.56- 5.81); p<0.001) and BNT-BNT (5377 (4596- 6289); GMR 5.66 (4.49- 7.15); p<0.001). By 12 weeks after dose two, S-antibody GMC had declined in all groups and remained significantly lower for ChAd-ChAd compared to ChAd-BNT (GMR 5.12 (3.79- 6.92); p<0.001), BNT-ChAd (GMR 4.1 (2.96- 5.69); p<0.001) and BNT-BNT (GMR 6.06 (4.32- 8.50); p<0.001). Previously infected adults had higher S-antibody GMC compared to infection-naive adults at all time-points and with all vaccine schedules. Conclusions These real-world findings demonstrate heterologous schedules with adenoviral-vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Background Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity or outcomes of reinfection in children. Methods We used national SARS-CoV-2 testing data in England to estimate the risk of reinfection >90 days after primary infection from 01 January 2020 to 31 July 2021, which encompassed both the Alpha and Delta waves in England. Disease severity was assessed by linking reinfection cases to national hospitalisation, intensive care admission and death registrations datasets. Findings Reinfection rates closely followed community infection rates, with a small peak during the Alpha wave and a larger peak during the Delta wave. In children aged <16 years, there were 688,418 primary infections and 2,343 reinfections. The overall reinfection rate was 66.88/100,000 population, being higher in adults (72.53/100,000) than in children (21.53/100,000). Reinfection rates after primary infection were 0.68% overall, 0.73% in adults and 0.34% in children. Of the 109 reinfections in children admitted to hospital, 78 (72%) had underlying comorbidities. Hospitalisation rates were similar for the first (64/2343, 2.73%) and second episode (57/2343, 2.43%). Intensive care admission was rare after primary infection (n=7) or reinfection (n=4), mainly in children with comorbidities. 44 deaths occurred after primary infection within 28 days of diagnosis (44/688,418, 0.01%), none after possible reinfections. Interpretation The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the Delta variant wave. Children had a lower risk of reinfection than adults, but reinfections were not associated with more severe disease or fatal outcomes. Funding PHE/UKHSA
Subject(s)
COVID-19 , von Willebrand Disease, Type 3 , DeathABSTRACT
Background This study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D). Methods Prospective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms. summary Losses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.
Subject(s)
COVID-19 , DyspneaABSTRACT
Adults receiving heterologous prime-boost COVID-19 immunisation schedules with mRNA (Pfizer-BioNTech) or adenoviral-vector (ChAdOx1-S/nCOV-19) vaccines had higher reactogenicity rates and were more likely to seek medical attention after their second dose than homologous schedules. Reactogenicity rates were generally higher among ≤50 than >50 year-olds and in adults with prior symptomatic or confirmed COVID-19. Adults receiving heterologous schedules because of severe first-dose reactions had lower reactogenicity after the second dose following ChAdOx1-S/Pfizer-BioNTech (93.4%[90.5-98.1] vs. 48%[41.0-57.7]) but not Pfizer-BioNTech/ChAdOx1-S (91.7%[77.5-98.2] vs. 75.0%[57.8-87.9]).