Association between antibody responses post-vaccination and severe COVID-19 outcomes: national population-based cohort study in Scotland (preprint)

Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity (≥five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05 - 29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63 - 18.29]) of these serious outcomes compared to those with high antibody levels.

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

Isolated but not alone: critical care communication in the time of covid-19

Many communication challenges became evident when the coronavirus pandemic led to the closure of Critical Care Units to visitors. Extra staff drafted in were unfamiliar with the ICU environment and needed to focus on direct patient care. The increased ICU footprint meant calls might be misdirected. Personal protective equipment (PPE) hampered hearing, speaking and phone use. Staff were unable to hold face-to-face family meetings and families were unable to be at the bedside which would, in normal times, enable them to be part of the patient’s hospital journey. Inevitably, this all led to an increased volume of phone calls.To try to solve some of these issues, it was decided that a dedicated team was needed to establish open lines of communication between patient, family and staff. A group of senior nurses from across the hospital were brought together to form the Critical Care Family Liaison Team (FLT).FLT now give coordinated information and are the first point of contact for families. Interventions include using technology such as FaceTime and Zoom to allow ‘virtual visiting’, conference calling for family updates, bedside photographs, voice recordings sent in by families and music playlists.The role for the FLT has evolved;the team was set up rapidly at the start of lockdown and members were in their new roles within a week. Daily verbal feedback was gathered from the medical team and interventions changed as necessary.It is difficult to assess what the situation would have been without this innovation. Formal feedback was requested from all staff members working in Critical Care and from patients and their families. Qualitative and 5 point likert scale responses have been positive. Further data collection and feedback is ongoing to ensure the service continues to evolve as we move towards a new normal.