Clinical outcomes of myocarditis after SARS-CoV-2 mRNA vaccination in four Nordic countries: population based cohort study

Objective To investigate the clinical outcomes of myocarditis associated with mRNA vaccines against the SARS-CoV-2 virus compared with other types of myocarditis. Design Population based cohort study. Setting Nationwide register data from four Nordic countries (Denmark, Finland, Norway, and Sweden), from 1 January 2018 to the latest date of follow-up in 2022. Participants The Nordic myocarditis cohort;7292 individuals aged ≥12 years who had an incident diagnosis of myocarditis as a main or secondary diagnosis, in a population of 23 million individuals in Denmark, Finland, Norway, and Sweden. Main outcome measures Heart failure, or death from any cause within 90 days of admission to hospital for new onset myocarditis, and hospital readmission within 90 days of discharge to hospital for new onset myocarditis. Clinical outcomes of myocarditis associated with SARS-CoV-2 mRNA vaccination, covid-19 disease, and conventional myocarditis were compared. Results In 2018-22, 7292 patients were admitted to hospital with new onset myocarditis, with 530 (7.3%) categorised as having myocarditis associated with SARS-CoV-2 mRNA vaccination, 109 (1.5%) with myocarditis associated with covid-19 disease, and 6653 (91.2%) with conventional myocarditis. At the 90 day follow-up, 62, nine, and 988 patients had been readmitted to hospital in each group (vaccination, covid-19, and conventional myocarditis groups, respectively), corresponding to a relative risk of readmission of 0.79 (95% confidence interval 0.62 to 1.00) and 0.55 (0.30 to 1.04) for the vaccination type and covid-19 type myocarditis groups, respectively, compared with the conventional myocarditis group. At the 90 day follow-up, 27, 18, and 616 patients had a diagnosis of heart failure or died in the vaccination type, covid-19 type, and conventional myocarditis groups, respectively. The relative risk of heart failure within 90 days was 0.56 (95% confidence interval 0.37 to 0.85) and 1.48 (0.86 to 2.54) for myocarditis associated with vaccination and covid-19 disease, respectively, compared with conventional myocarditis;the relative risk of death was 0.48 (0.21 to 1.09) and 2.35 (1.06 to 5.19), respectively. Among patients aged 12-39 years with no predisposing comorbidities, the relative risk of heart failure or death was markedly higher for myocarditis associated with covid-19 disease than for myocarditis associated with vaccination (relative risk 5.78, 1.84 to 18.20). Conclusions Compared with myocarditis associated with covid-19 disease and conventional myocarditis, myocarditis after vaccination with SARS-CoV-2 mRNA vaccines was associated with better clinical outcomes within 90 days of admission to hospital.

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.

Coronavirus immunisation abroad among foreign-born persons in Norway. / Koronavaksinering i utlandet blant utenlandsfødte.

BACKGROUND: The Norwegian Institute of Public Health's statistics on immunisation against SARS-CoV-2 show that vaccination coverage for foreign-born persons living in Norway is lower than for persons born in Norway. As of January 2022, the difference was 18 percentage points (76 % versus 94 %). This difference is likely to be due to several factors, one of which may be that many of those who were immunised abroad have not had this registered in the Norwegian Immunisation Registry. MATERIAL AND METHOD: In November 2021, the Norwegian Institute of Public Health conducted a public health survey in the county of Viken. Respondents were asked if they had been vaccinated against the coronavirus, if they were vaccinated in Norway or abroad, and if immunisation abroad had been reported to the Norwegian health service. They were also asked to specify their country of birth. The sample was drawn from the National Population Register. The survey was conducted online and the response rate was 41 % (n = 108 738). RESULTS: A total of 105 010 (97 %) of the respondents had had at least one dose of the coronavirus vaccine. Of these, 724 (<1 %) had only been vaccinated abroad. This applied to 392 (3 %) of the 13 286 foreign-born persons, 203 (52 %) of whom had reported their immunisation to the Norwegian health service. INTERPRETATION: In this dataset, unregistered immunisation abroad explains only a small proportion of the difference in vaccination coverage between Norwegian-born and foreign-born persons.

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents.

Importance: Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged. Objective: To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age. Design, Setting, and Participants: Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden. Exposures: The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2. Main Outcomes and Measures: Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals. Results: Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar. Conclusions and Relevance: Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

Risk factors for SARS-CoV-2 infection and hospitalisation in children and adolescents in Norway: a nationwide population-based study.

OBJECTIVE: To determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents. DESIGN: Nationwide, population-based cohort study. SETTING: Norway from 1 March 2020 to 30 November 2021. PARTICIPANTS: All Norwegian residents<18 years of age. MAIN OUTCOME MEASURES: Population-based healthcare and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin and pre-existing chronic comorbidities. All residents were followed until age 18 years, emigration, death or end of follow-up. HRs estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated. RESULTS: Of 1 219 184 residents, 82 734 (6.7%) tested positive by PCR or lateral flow tests, of whom 241 (0.29%) were admitted to a hospital. Low family income (adjusted HR (aHR) 1.26, 95% CI 1.23 to 1.30), crowded housing (1.27, 1.24 to 1.30), household size, age, non-Nordic country of origin (1.63, 1.60 to 1.66) and area of living were independent risk factors for infection. Chronic comorbidity was associated with a slightly lower risk of infection (aHR 0.90, 95% CI 0.88 to 0.93). Chronic comorbidity was associated with hospitalisation (aHR 3.46, 95% CI 2.50 to 4.80), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected. CONCLUSIONS: Socioeconomic factors, country of origin and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with higher risk of admission but slightly lower overall risk of acquiring SARS-CoV-2.

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study.

OBJECTIVE: To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations. DESIGN: Population based cohort study. SETTING: Nationwide healthcare registers in Denmark and Norway. PARTICIPANTS: All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts. MAIN OUTCOME MEASURES: Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries. RESULTS: The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected. CONCLUSIONS: Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Deaths after confirmed SARS-CoV-2 in Norway. / Dødsfall etter påvist SARS-CoV-2 i Norge.

BACKGROUND: Advanced age is the most important risk factor for death as a result of COVID-19, but there is a dearth of knowledge regarding the impact of chronic diseases. Using health registry data, we describe the disease profiles of persons who died after a confirmed infection with SARS-CoV-2 during the first three months of the pandemic in Norway. MATERIAL AND METHOD: Data from the specialist health service (Norwegian Patient Registry, NPR) and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) were linked to information on positive tests for SARS-CoV-2 from the Norwegian Surveillance System for Communicable Diseases (MSIS) and on deaths from the National Population Register. The data retrieval included the Norwegian population as of 1 March 2020 with data for confirmed infections, hospitalisations and deaths until 31 May 2020. RESULTS: Of 8 412 persons with a confirmed SARS-CoV-2 infection, altogether 244 (2.9 %) died, whereof 133 (55 %) were men. Among those with a confirmed infection, the proportion who died varied from 0.2 % (age < 60 years) to 52 % (age ≥ 90 years). Altogether 92 (38 %) patients died in hospital. 25 (16 %) of those who died elsewhere had previously been hospitalised for COVID-19. The proportion with no registered chronic disease was 39 % in the age group < 70 years and 26 % in the age group ≥ 70 years. The disease distribution varied between those patients who had died in and outside of hospital, especially for diagnoses of diabetes, renal failure and dementia. INTERPRETATION: Among those who had a SARS-CoV-2 infection confirmed during the first three months of the pandemic in Norway, only a small proportion died. The majority of those who died were 70 years or older and had at least one chronic disease, but the disease profile varied between patients who died in and outside of hospital. Health registry data can help provide a better overview of and advice to risk groups in the population during an ongoing pandemic.

Underlying conditions in adults with COVID-19. / Underliggende tilstander hos voksne med covid-19.

BACKGROUND: Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population. MATERIAL AND METHOD: We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020. RESULTS: Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions. INTERPRETATION: Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.

SARS-CoV-2 in children and adolescents in Norway: confirmed infection, hospitalisations and underlying conditions. / Sars-CoV-2 hos barn og ungdom i Norge: påvist smitte, sykehusinnleggelser og underliggende tilstander.

BACKGROUND: Children and adolescents are at lower risk of disease caused by SARS-CoV-2. We describe the incidence of confirmed infection and hospitalisation of children and adolescents under the age of 20 in Norway, and specifically among those with underlying conditions. MATERIAL AND METHOD: The Norwegian Directorate of Health has collaborated with the Norwegian Institute of Public Health on the establishment of a data extraction system to monitor the coronavirus outbreak. Data from the specialist health service (Norwegian Patient Registry, NPR), and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) are linked to data on positive SARS-CoV-2 tests from the Surveillance System for Communicable Diseases (MSIS). This covers all persons living in Norway as of 1 March 2020, with data on confirmed infection up to and including 13 May 2020 and on hospitalisations up to and including 30 April 2020. RESULTS: Of 8 125 persons with confirmed SARS-CoV-2 in the whole population, 493 (6.1 %) were under 20 years old. The median age of the under-20s was 15 years, and 252 (51 %) were girls. 3 % were hospitalised. No deaths were registered among patients aged under 20 in Norway. We found a somewhat larger share with confirmed SARS-CoV-2 in the group with diseases of the neuromuscular system. INTERPRETATION: Few children and adolescents have had SARS-CoV-2 confirmed, and only a very few have been hospitalised. Underlying conditions may result in a lower threshold for testing, and hence a higher incidence of confirmed infection in this group, although higher risk cannot be excluded.