Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort study.

BACKGROUND AND AIMS: The SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. The aim was to evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. METHODS: A multinational cohort study was conducted using nationwide register data in Denmark, Finland, Norway, and Sweden and comprising all 8.9 million individuals residing in each of the four countries. Participants were followed for an inpatient diagnosis of myocarditis. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis comparing vaccination schedules, with associated 95% confidence intervals (CIs). Country-specific results were combined in meta-analyses. RESULTS: A total of 8.9 million residents were followed for 12 271 861 person-years and 1533 cases of myocarditis were identified. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after the second dose [IRR 2.08 (95% CI 1.31-3.33) and 8.89 (2.26-35.03), respectively]. For females, the corresponding IRR was only estimable for BNT162b2, 3.99 (0.41-38.64). The corresponding absolute risks following the third dose of BNT162b2 and mRNA-1273 in males were 0.86 (95% CI 0.53-1.32) and 1.95 (0.53-4.99) myocarditis events within 28 days per 100 000 individuals vaccinated, respectively. In females, the corresponding absolute risks following the third dose of BNT162b2 were 0.15 (0.04-0.39) events per 100 000 individuals vaccinated. No deaths occurred within 30 days of vaccine-related cases. CONCLUSIONS: The results suggest that a booster dose is associated with increased myocarditis risk in adolescents and young adults. However, the absolute risk of myocarditis following booster vaccination is low.

Underreporting of SARS-CoV-2 infections during the first wave of the 2020 COVID-19 epidemic in Finland-Bayesian inference based on a series of serological surveys.

In Finland, the first wave of the COVID-19 epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took place from March to June 2020, with the majority of COVID-19 cases diagnosed in the Helsinki-Uusimaa region. The magnitude and trend in the incidence of COVID-19 is one way to monitor the course of the epidemic. The diagnosed COVID-19 cases are a subset of the infections and therefore the COVID-19 incidence underestimates the SARS-CoV-2 incidence. The likelihood that an individual with SARS-CoV-2 infection is diagnosed with COVID-19 depends on the clinical manifestation as well as the infection testing policy and capacity. These factors may fluctuate over time and the underreporting of infections changes accordingly. Quantifying the extent of underreporting allows the assessment of the true incidence of infection. To obtain information on the incidence of SARS-CoV-2 infection in Finland, a series of serological surveys was initiated in April 2020. We develop a Bayesian inference approach and apply it to data from the serological surveys, registered COVID-19 cases, and external data on antibody development, to estimate the time-dependent underreporting of SARS-Cov-2 infections during the first wave of the COVID-19 epidemic in Finland. During the entire first wave, there were 1 to 5 (95% probability) SARS-CoV-2 infections for every COVID-19 case. The underreporting was highest before April when there were 4 to 17 (95% probability) infections for every COVID-19 case. It is likely that between 0.5%-1.0% (50% probability) and no more than 1.5% (95% probability) of the adult population in the Helsinki-Uusimaa region were infected with SARS-CoV-2 by the beginning of July 2020.

Incidence of sinus thrombosis with thrombocytopenia-A nation-wide register study.

Safe vaccination is essential for mitigation of the COVID-19 pandemic. Two adenoviral vector vaccines, ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson&Johnson/Janssen) have shown to be effective and they are distributed globally, but reports on serious cerebral venous sinus thrombosis (CVST) associated with thrombocytopenia, have emerged. Our objective was to evaluate the background incidence of CVST with thrombocytopenia and to compare it to incidences following COVID-19 vaccines. We conducted a register-based nation-wide cohort study in Finland, including all 5.5 million individuals alive in Finland, 1 Jan 2020. COVID-19 vaccinations registered in the National Vaccination Register served as the exposure. We detected CVST admissions or hospital visits recorded in the hospital discharge register from Jan 1, 2020 through April 2, 2021. We confirmed the diagnosis of CVST and thrombocytopenia (platelet count <150,000 per cubic millimeter) using radiology reports and laboratory data. By Poisson regression, we compared the baseline incidences to the risks within four weeks after COVID-19 vaccinations. Out of the 167 CVST episodes identified in the registers, 117 were confirmed as CVST, 18 of which coincided with thrombocytopenia (baseline incidence 0.18 per 28 days per million persons). We found 2 episodes of CVST with thrombocytopenia within 28 days of the first ChAdOx1 nCov-19 vaccination (among 200,397 vaccinated, aged 16 or above). No cases were found following the first mRNA vaccine dose among 782,604 vaccinated. The background incidence of CVST combined with thrombocytopenia was minuscule compared to the incidence during the weeks following the ChAdOx1 nCov-19 vaccination. Accurate estimation of the baseline incidence is essential in the critical appraisal of the benefit-risk of any vaccination program.

Sudden Hearing Loss Following Vaccination Against COVID-19.

Importance: Spontaneous adverse reaction reports of sudden hearing loss have been observed, and a population-based cohort study conducted in Israel showed an increase in the incidence of sudden sensorineural hearing loss (SSNHL) following vaccination with messenger RNA COVID-19 vaccine BNT162b2 (Pfizer-BioNTech). However, in this setting, the possibility of confounding remained. Objective: To assess a potential association between COVID-19 vaccinations and SSNHL. Design, Setting, and Participants: This register-based country-wide retrospective cohort study of 5.5 million Finnish residents was conducted from January 1, 2019, to April 20, 2022, and included all individuals who were identified from the population information system who were alive or born during the study period except individuals who had SSNHL during 2015 to 2018 according to specialized care derived diagnosis codes for SSNHL (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code H91.2) as a primary or secondary diagnosis. Exposures: The a priori primary risk period was 0 to 54 days following each COVID-19 vaccination. The risk periods for different vaccine doses did not overlap so that a later vaccine exposure ended the previous risk period. The secondary risk period was from 55 days following each COVID-19 vaccination until a subsequent COVID-19 vaccination. A secondary analysis included a risk time from 0 to 54 days following a positive polymerase chain reaction test result for SARS-CoV-2. Main Outcomes and Measures: The incidences of SSNHL following COVID-19 vaccination were compared with the incidences before the COVID-19 epidemic in Finland. The Poisson regression model included calendar time, age, sex, diabetes, cardiovascular disease, other chronic diseases, and the number of visits in primary health care. Results: For the 5.5 million Finnish residents included in the study, the comparison time comprised 6.5 million person-years, the primary risk time of 1.7 million person-years, and the secondary risk time of 2.1 million person-years. Before the COVID-19 epidemic in Finland, 18.7/100 000 people received a diagnosis of SSNHL annually. The study data suggested no increased risk for SSNHL following any COVID-19 vaccination. In particular, adjusted incidence rate ratios with 95% confidence intervals for the BNT162b2 vaccine's 3 doses were 0.8 (95% CI, 0.6-1.0), 0.9 (95% CI, 0.6-1.2), and 1.0 (95% CI, 0.7-1.4), respectively. There was no association between SARS-CoV-2 infection and an increased incidence of SSNHL. Conclusions and Relevance: The results of this cohort study show no evidence of an increased risk of SSNHL following COVID-19 vaccination. The study accounted for previous disease and other potential confounding factors. These results are based on diagnosis codes in specialized care but still need to be verified in settings that are capable of evaluating the degree of hearing loss.

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.