COVID-19 Vaccine Safety in Pregnancy, A Nested Case-Control Study in Births From April 2021 to March 2022, England.

OBJECTIVE: Assessment of COVID-19 vaccine safety in pregnancy using population-based data. DESIGN: Matched case-control study nested in a retrospective cohort. SETTING: April 2021-March 2022, England. POPULATION OR SAMPLE: All pregnant individuals aged between 18 and 50 years with valid health records. METHODS: Individuals identified from the national Maternity Services Data Set (MSDS) had their records linked to hospital admission, national COVID-19 vaccine and COVID-19 testing databases. Matching included participant's age and estimated week of conception. We compared outcomes across multiple COVID-19 vaccine exposures using conditional multivariable logistic regression, adjusting for demographic and health characteristics. MAIN OUTCOME MEASURES: Adverse pregnancy, maternal and neonatal outcomes. RESULTS: 514 013 individuals were included. We found 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 < 7 at 5 min of age (aOR = 0.89, 95% CI: 0.80-0.98) for individuals who received at least one dose of COVID-19 vaccine during pregnancy. The odds of admission to intensive care unit during pregnancy were lower in those vaccinated (aOR = 0.85, 95% CI: 0.76-0.95). There was no association between vaccination in pregnancy and stillbirth, neonatal death, perinatal death and maternal venous thromboembolism in pregnancy. CONCLUSIONS: COVID-19 vaccines are safe to use in pregnancy. Our findings generated important information to communicate to pregnant individuals and health professionals to support COVID-19 maternal vaccination programmes.

Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. METHODS AND FINDINGS: CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. CONCLUSIONS: COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

Assessment of mortality and hospital admissions associated with confirmed infection with SARS-CoV-2 Alpha variant: a matched cohort and time-to-event analysis, England, October to December 2020.

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.

Temporal changes to adult case fatality risk of COVID-19 after vaccination in England between May 2020 and February 2022: a national surveillance study.

OBJECTIVES: Risk of death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has fallen during the pandemic, largely due to immunity from vaccination. In England, the timing and extent of this reduction varied due to staggered eligibility during the primary vaccination campaign, based on age and clinical risk group. Duration of protection is less well understood. Our objective was to estimate the case fatality risk (CFR) by vaccination status and time since last dose during a period of widespread community testing, to better understand the impact of coronavirus disease 2019 (COVID-19) vaccination and duration of protection. DESIGN: SARS-CoV-2 cases diagnosed between May 2020 and February 2022 were linked to vaccine records from the National Immunisation Management System. CFR was calculated as the proportion of cases that died of COVID-19 per the death certificate, aggregated by week of specimen and stratified by 10-year age band and vaccination status. SETTING: England, UK. PARTICIPANTS: A total of 10,616,148 SARS-CoV-2 cases, aged ≥18 years, recorded by England's laboratory reporting system. MAIN OUTCOME MEASURES: Case fatality risk of COVID-19, stratified by age band and vaccination status. RESULTS: Overall, a reduction in CFR was observed for all age bands, with a clear temporal link to when the age group became eligible for primary vaccination and then the first booster. CFR increased with age (0.3% 50-59 years; 1.2% 60-69; 4.7% 70-79; 16.3% 80+) and was highest in the unvaccinated - albeit a reduction was observed over time. The highest CFR was seen in the unvaccinated 80+ group prior to vaccination rollout (30.6%). CFR was consistently lowest in vaccinated populations within 6 months of last dose, yet increased after over 6 months elapsed since last dose, across all age bands. CONCLUSIONS: COVID-19 CFR reduced after vaccination, with the lowest CFR seen across all age bands when vaccinated up to 6 months prior to specimen date. This provides some evidence for continued booster doses in older age groups.

Yersinia pestis genomes reveal plague in Britain 4000 years ago.

Extinct lineages of Yersinia pestis, the causative agent of the plague, have been identified in several individuals from Eurasia between 5000 and 2500 years before present (BP). One of these, termed the 'LNBA lineage' (Late Neolithic and Bronze Age), has been suggested to have spread into Europe with human groups expanding from the Eurasian steppe. Here, we show that the LNBA plague was spread to Europe's northwestern periphery by sequencing three Yersinia pestis genomes from Britain, all dating to ~4000 cal BP. Two individuals were from an unusual mass burial context in Charterhouse Warren, Somerset, and one individual was from a single burial under a ring cairn monument in Levens, Cumbria. To our knowledge, this represents the earliest evidence of LNBA plague in Britain documented to date. All three British Yersinia pestis genomes belong to a sublineage previously observed in Bronze Age individuals from Central Europe that had lost the putative virulence factor yapC. This sublineage is later found in Eastern Asia ~3200 cal BP. While the severity of the disease is currently unclear, the wide geographic distribution within a few centuries suggests substantial transmissibility.

Reciprocal influences of tobacco use on illicit opioid and alcohol use during the first six-months of specialist addiction treatment.

BACKGROUND: This is the first national study of lagged reciprocal associations between tobacco smoking frequency and change in illicit opioid or alcohol use frequency within six-months of treatment. METHODS: All adults admitted to publicly-funded specialist addiction treatment in England in 2018/19 and enrolled for at least six months for either opioid use disorder (OUD; n = 22,046; 82.4 % of those eligible) or alcohol use disorder (AUD; n = 15,251; 78.8 % of those eligible). Two cross-lagged panel models estimated, separately for OUD and AUD patients, the relationships between smoking at admission and change in main drug over six months, and between main drug use at admission and change in smoking over six months. RESULTS: Within the OUD cohort, illicit opioid use frequency reduced from 17.7 days to 8.0 days and smoking tobacco remained at 18.8 days. After controlling for available covariates, higher smoking frequency at admission was associated with a relative increase in illicit opioid use at six-months (0.02 days [95 % CI 0.00-0.03]). Within the AUD cohort, alcohol use frequency reduced from 21.2 days to 14.4 days while smoking tobacco reduced from 12.6 days to 11.5 days. Higher smoking frequency at admission was associated with a relative increase in alcohol use at six-months (0.03 days [95 % CI 0.02-0.04]) and higher alcohol use frequency at admission was associated with a relative increase in smoking at six-months (0.04 [95 % CI 0.02-0.06]), controlling for available covariates. CONCLUSIONS: Higher smoking frequency at admission is associated with higher illicit opioid and alcohol use frequency after six-months of specialist addiction treatment.