COVID-19 vaccination and SARS-CoV-2 infection in early pregnancy and the risk of major congenital anomalies: a national population-based cohort study (preprint)

Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. We conducted a national, population-based, matched cohort study to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any congenital anomaly and; [2] non-genetic anomalies. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6,731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any congenital anomaly and 120 had a non-genetic anomaly. Primary analyses found no association between vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83–1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81–1.22). Primary analyses also found no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66–1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57–1.54). Findings were robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.

Early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection: a national population-based matched cohort study (preprint)

There are limited data regarding the safety of COVID-19 vaccines in early pregnancy. This may contribute to vaccine hesitancy in people who are pregnant, or who are planning pregnancy. We conducted a population-level matched cohort study assessing associations between COVID-19 vaccination and miscarriage (pregnancy loss prior to 20 weeks gestation) and ectopic pregnancy. We used electronic health records of all female residents in Scotland who were vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Primary analyses used unvaccinated women from the pre-pandemic period as controls (historical controls) matched (3:1) on maternal age, gestational age at vaccination, and season of conception; with adjustment for maternal deprivation level, rural/urban status and clinical vulnerability. Supplementary analyses used unvaccinated women from the pandemic period as controls (contemporary controls). Analyses of outcomes following SARS-CoV-2 infection were undertaken with infection rather than vaccination as the exposure. Following COVID-19 vaccination, the rate of miscarriage was 9.1% (n = 1,716) and ectopic pregnancy 1.2% (n = 126). Primary analyses found no association between vaccination and miscarriage (adjusted Odds Ratio [aOR] = 1.02, 95% Confidence Interval [CI] = 0.96–1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92–1.38). Primary analyses also found no association between SARS-CoV-2 infection and miscarriage or ectopic pregnancy. Results of supplementary analyses were similar to primary analyses. Given that SARS-CoV-2 infection in later pregnancy carries substantial risks to women and babies, our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.

Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study (preprint)

ObjectiveTo examine infants in Scotland aged 0-27 days with confirmed SARS-CoV-2 infection; the risk of neonatal infection by factors including maternal infection status and gestation at birth; and the need for hospital admission among infected neonates. DesignPopulation-based cohort study. Setting and populationAll live births in Scotland, 1 March 2020 to 31 January 2022. ResultsThere were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100,000 live births (141/92,009). Among infants born to women with confirmed infection around the time of birth, the infection rate was 1,811 per 100,000 live births (15/828). Nearly two-thirds (92/141, 65.2%) of babies with confirmed neonatal infection had an associated admission to neonatal or (more commonly) paediatric care. Of those admitted to hospital, 6/92 (6.5%) infants were admitted to neonatal or paediatric intensive care, however none of these six had COVID-19 recorded as the main diagnosis underlying their admission. There were no neonatal deaths among babies with confirmed infection. Implications and relevanceConfirmed neonatal SARS-CoV-2 infection is uncommon. Secular trends in the neonatal infection rate broadly follow those seen in the general population, albeit at a lower level. Maternal infection at birth increases the risk of neonatal infection, but most babies with neonatal infection are born to women without confirmed infection. A high proportion of neonates with confirmed infection are admitted to hospital, with resulting implications for the baby, family, and services, although their outcomes are generally good. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIThe incidence of SARS-CoV-2 infection in neonates is low, but some studies have suggested that age under 1 month is a risk factor for severe infection requiring admission to intensive care. C_LIO_LIAlmost all the studies of neonatal SARS-CoV-2 have focused on the transmission risk from SARS-CoV-2 positive women to their offspring and data are lacking on the level of neonatal SARS-CoV-2 infection in the whole population. C_LI What this study addsO_LIThis study includes all babies with confirmed SARS-CoV-2 in the neonatal period in Scotland during the first 22 months of the COVID-19 pandemic. C_LIO_LIConfirmed neonatal SARS-CoV-2 infection is uncommon, but a high proportion of neonates with confirmed infection are admitted to hospital. C_LIO_LIConfirmed maternal SARS-CoV-2 infection around the time of birth substantially increases the risk of neonatal infection, although the absolute risk of neonatal infection remains low (<2%) and most babies with neonatal infection are born to women without confirmed infection. C_LIO_LIOutcomes for neonates with confirmed SARS-CoV-2 infection are good; only 6.5% (6/92) of admitted neonates required intensive care, and COVID-19 was not the primary diagnosis recorded for these babies. There were no neonatal deaths among babies with confirmed infection. C_LI

An External Validation of the QCovid Risk Prediction Algorithm for Risk of Mortality from COVID-19 in Adults: National Validation Cohort Study in Scotland (preprint)

Background: The QCovid algorithm is a risk prediction tool for COVID-19 hospitalisation and mortality that can be used to stratify patients by risk into vulnerability groups . We carried out an external validation of the QCovid algorithm in Scotland.Methods: We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription polymerase chain reaction (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisation and deaths in our dataset for two time periods: 1 March, 2020 to 30 April, 2020, and 1 May, 2020 to 30 June, 2020.Findings: Our dataset comprised 5,384,819 individuals, representing 99% of the estimated population (5,463,300) resident in Scotland in 2020. The algorithm showed excellent calibration in both time periods with close correspondence between observed and predicted risks. Harrell ’s C for deaths in males and females in the first period was 0.946 (95% CI: 0.941 - 0.951) and 0.925 (95% CI: 0.919 - 0.931) respectively. Harrell’s C for hospitalisations in males and females in the first period was 0.809 (95% CI: 0.801 - 0.817) and 0.816 (95% CI: 0.808 - 0.823) respectively.Interpretation: The QCovid algorithm shows high levels of external validity in predicting the risk of COVID- 19 hospitalisation and death in the population of Scotland.Funding: Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, funded through the UK Research and Innovation Industrial Strategy Challenge Fund Health Data Research UK.Declaration of Interests: Dr. Hippisley-Cox reports grants from MRC, grants from Wellcome Trrust, grants from NIHR, during the conduct of the study; other from ClinRisk Ltd, outside the submitted work. Dr. Sheikh reports grants from NIHR, grants from MRC, grants from HRR UK, during the conduct of the study. All other authors report no conflict of interest.Ethics Approval Statement: Ethical permission for this study was granted from South East Scotland Research Ethics Committee 02 [12/SS/0201]. The Public Benefit and Privacy Panel Committee of Public Health Scotland, approved the linkage and analysis of the de-identified datasets for this project [1920-0279].

Effectiveness of First Dose of COVID-19 Vaccines Against Hospital Admissions in Scotland: National Prospective Cohort Study of 5.4 Million People (preprint)

Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines have demonstrated high efficacy against infection in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. There is an urgent need to study the ‘real-world’ effects of these vaccines. The aim of our study was to estimate the effectiveness of the first dose of these COVID-19 vaccines in preventing hospital admissions.Methods: We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database comprising of linked vaccination, primary care, Real-Time Polymerase Chain Reaction (RT-PCR) testing, hospitalisation and mortality records for 5.4 million people in Scotland (covering ~99% of population). A time-dependent Cox model and Poisson regression models were fitted to estimate effectiveness against COVID-19 related hospitalisation (defined as 1- Adjusted Hazard Ratio) following the first dose of vaccine.Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%; 95% CI 65 to 90 at 28-34 days post-vaccination).Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.Funding: UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Health Data Research UK.Conflict of Interest: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. All other authors report no conflicts of interest.Ethical Approval: Approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279).