Stroke After SARS-CoV-2 mRNA Vaccine: A Nationwide Registry Study.

BACKGROUND: Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain. METHODS: In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident. RESULTS: The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85-1.00) and 0.89 (0.73-1.08) for ischemic stroke, 0.81 (0.67-0.98) and 1.05 (0.64-1.71) for intracerebral hemorrhage, and 0.64 (0.46-0.87) and 1.12 (0.57-2.19) for subarachnoid hemorrhage, respectively. CONCLUSIONS: We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

Effectiveness of BNT162b2 vaccine against SARS-CoV-2 Delta and Omicron infection in adolescents, Norway, August 2021 to January 2022.

OBJECTIVES: We estimated the BNT162b2 vaccine effectiveness (VE) against any (symptomatic or not) SARS-CoV-2 Delta and Omicron infection among adolescents (aged 12-17 years) in Norway from August 2021 to January 2022. METHODS: We used Cox proportional hazard models, where vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, residence county, birth country, and living conditions. RESULTS: The VE against Delta infection peaked at 68% (95% confidence interval [CI]: 64-71%) and 62% (95% CI: 57-66%) in days 21-48 after the first dose among those aged 12-15 years and 16-17 years, respectively. Among those aged 16-17 years who received two doses, the VE against Delta infection peaked at 93% (95% CI: 90-95%) in days 35-62 and decreased to 84% (95% CI: 76-89%) in ≥63 days after vaccination. We did not observe a protective effect against Omicron infection after receiving one dose. Among those aged 16-17 years, the VE against Omicron infection peaked at 53% (95% CI: 43-62%) in 7-34 days after the second dose and decreased to 23% (95% CI: 3-40%) in ≥63 days after vaccination. CONCLUSION: We found a reduced protection after two BNT162b2 vaccine doses against any Omicron infection compared to Delta. Effectiveness decreased with time from vaccination for both variants. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during the Omicron dominance.

Short-term safety of COVID-19 mRNA vaccines with respect to all-cause mortality in the older population in Norway.

BACKGROUND: There have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used. METHODS: In this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from theNorwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group. RESULTS: Between December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 [95% CI: 0.24-0.31]). Similar results were obtained in analyses stratified by use of health services and age group. CONCLUSION: We found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality.

Age-Specific Estimates of Respiratory Syncytial Virus-Associated Hospitalizations in 6 European Countries: A Time Series Analysis.

BACKGROUND: Knowledge on age-specific hospitalizations associated with RSV infection is limited due to limited testing, especially in older children and adults in whom RSV infections are not expected to be severe. Burden estimates based on RSV coding of hospital admissions are known to underestimate the burden of RSV. We aimed to provide robust and reliable age-specific burden estimates of RSV-associated hospital admissions based on data on respiratory infections from national health registers and laboratory-confirmed cases of RSV. METHODS: We conducted multiseason regression analysis of weekly hospitalizations with respiratory infection and weekly laboratory-confirmed cases of RSV and influenza as covariates, based on national health registers and laboratory databases across 6 European countries. The burden of RSV-associated hospitalizations was estimated by age group, clinical diagnosis, and presence of underlying medical conditions. RESULTS: Across the 6 European countries, hospitalizations of children with respiratory infections were clearly associated with RSV, with associated proportions ranging from 28% to 60% in children younger than 3 months and we found substantial proportions of admissions to hospital with respiratory infections associated with RSV in children younger than 3 years. Associated proportions were highest among hospitalizations with ICD-10 codes of "bronchitis and bronchiolitis." In all 6 countries, annual incidence of RSV-associated hospitalizations was >40 per 1000 persons in the age group 0-2 months. In age group 1-2 years the incidence rate ranged from 1.3 to 10.5 hospitalizations per 1000. Adults older than 85 years had hospitalizations with respiratory infection associated to RSV in all 6 countries although incidence rates were low. CONCLUSIONS: Our findings highlight the substantial proportion of RSV infections among hospital admissions across different ages and may help public health professionals and policy makers when planning prevention and control strategies. In addition, our findings provide valuable insights for health care professionals attending to both children and adults presenting with symptoms of viral respiratory infections.

COVID-19 Hospitalization Among Children <18 Years by Variant Wave in Norway.

OBJECTIVES: There is limited evidence on whether the relative severity of coronavirus disease 2019 (COVID-19) in children and adolescents differs for different severe acute respiratory syndrome coronavirus 2 variants. We compare the risk of hospitalization to acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C) among unvaccinated persons <18 years with COVID-19 (cases) between waves of the Alpha, Delta, and Omicron (sublineage BA.1) variants in Norway. METHODS: We used linked individual-level data from national registries to calculate adjusted risk ratios (aRR) with 95% confidence interval (CI) using multivariable log-binomial regression. We adjusted for variant wave, demographic characteristics, and underlying comorbidities. RESULTS: We included 10 538 Alpha (21 hospitalized with acute COVID-19, 7 MIS-C), 42 362 Delta (28 acute COVID-19, 14 MIS-C), and 82 907 Omicron wave cases (48 acute COVID-19, 7 MIS-C). The risk of hospitalization with acute COVID-19 was lower in the Delta (aRR: 0.53, 95% CI: 0.30-0.93) and Omicron wave (aRR: 0.40, 95% CI: 0.24-0.68), compared to the Alpha wave. We found no difference in this risk for Omicron compared to Delta. The risk of MIS-C was lower for Omicron, compared to Alpha (aRR: 0.09, 95% CI: 0.03-0.27) and Delta (aRR: 0.26, 95% CI: 0.10-0.63). CONCLUSIONS: We do not find clear evidence that different variants have influenced the risk of hospitalization with acute COVID-19 among unvaccinated children and adolescents in Norway. The lower risk of this outcome with Omicron and Delta may reflect changes in other factors over time, such as the testing strategy, maternal vaccination and/or hospitalization criteria. The emergence of Omicron has reduced the risk of MIS-C.

Milder disease trajectory among COVID-19 patients hospitalised with the SARS-CoV-2 Omicron variant compared with the Delta variant in Norway.

Using individual-level national registry data, we conducted a cohort study to estimate differences in the length of hospital stay, and risk of admission to an intensive care unit and in-hospital death among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, compared with patients infected with Delta variant in Norway. We included 409 (38%) patients infected with Omicron and 666 (62%) infected with Delta who were hospitalised with coronavirus disease 2019 (COVID-19) as the main cause of hospitalisation between 6 December 2021 and 6 February 2022. Omicron patients had a 48% lower risk of intensive care admission (adjusted hazard ratios (aHR): 0.52, 95% confidence interval (CI): 0.34-0.80) and a 56% lower risk of in-hospital death (aHR: 0.44, 95%CI: 0.24-0.79) compared with Delta patients. Omicron patients had a shorter length of stay (with or without ICU stay) compared with Delta patients in the age groups from 18 to 79 years and those who had at least completed their primary vaccination. This supports growing evidence of reduced disease severity among hospitalised Omicron patients compared with Delta patients.

No difference in risk of hospitalization between reported cases of the SARS-CoV-2 Delta variant and Alpha variant in Norway.

OBJECTIVES: To estimate the risk of hospitalization among reported cases of the Delta variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with the Alpha variant in Norway, and the risk of hospitalization by vaccination status. METHODS: A cohort study was conducted on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. Adjusted risk ratios (aRR) with 95% confidence intervals (CI) were calculated using multi-variable log-binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities. RESULTS: In total, 7977 cases of the Delta variant and 12,078 cases of the Alpha variant were included in this study. Overall, 347 (1.7%) cases were hospitalized. The aRR of hospitalization for the Delta variant compared with the Alpha variant was 0.97 (95% CI 0.76-1.23). Partially vaccinated cases had a 72% reduced risk of hospitalization (95% CI 59-82%), and fully vaccinated cases had a 76% reduced risk of hospitalization (95% CI 61-85%) compared with unvaccinated cases. CONCLUSIONS: No difference was found between the risk of hospitalization for Delta cases and Alpha cases in Norway. The results of this study support the notion that partially and fully vaccinated cases are highly protected against hospitalization with coronavirus disease 2019.

Increased risk of hospitalisation and intensive care admission associated with reported cases of SARS-CoV-2 variants B.1.1.7 and B.1.351 in Norway, December 2020 -May 2021.

INTRODUCTION: Since their emergence, SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.351 have spread worldwide. We estimated the risk of hospitalisation and admission to an intensive care unit (ICU) for infections with B.1.1.7 and B.1.351 in Norway, compared to infections with non-VOC. MATERIALS AND METHODS: Using linked individual-level data from national registries, we conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway diagnosed between 28 December 2020 and 2 May 2021. Variants were identified based on whole genome sequencing, partial sequencing by Sanger sequencing or PCR screening for selected targets. The outcome was hospitalisation or ICU admission. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression to examine the association between SARS-CoV-2 variants B.1.1.7 and B.1.351 with i) hospital admission and ii) ICU admission compared to non-VOC. RESULTS: We included 23,169 cases of B.1.1.7, 548 B.1.351 and 4,584 non-VOC. Overall, 1,017 cases were hospitalised (3.6%) and 206 admitted to ICU (0.7%). B.1.1.7 was associated with a 1.9-fold increased risk of hospitalisation (aRR 95%CI 1.6-2.3) and a 1.8-fold increased risk of ICU admission (aRR 95%CI 1.2-2.8) compared to non-VOC. Among hospitalised cases, no difference was found in the risk of ICU admission between B.1.1.7 and non-VOC. B.1.351 was associated with a 2.4-fold increased risk of hospitalisation (aRR 95%CI 1.7-3.3) and a 2.7-fold increased risk of ICU admission (aRR 95%CI 1.2-6.5) compared to non-VOC. DISCUSSION: Our findings add to the growing evidence of a higher risk of severe disease among persons infected with B.1.1.7 or B.1.351. This highlights the importance of prevention and control measures to reduce transmission of these VOC in society, particularly ongoing vaccination programmes, and preparedness plans for hospital surge capacity.