Booster Vaccination with SARS-CoV-2 mRNA Vaccines and Myocarditis Risk in Adolescents and Young Adults: A Nordic Cohort Study of 8.9 Million Residents (preprint)

Importance 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. Few studies have evaluated the association after booster doses. Objective To evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. Design A multinational cohort study using nationwide register data. Setting Denmark, Finland, Norway, and Sweden. Participants Cohorts comprising all 8.9 million individuals residing in each of the four countries, born 1982-2009, and alive at start of study on December 27, 2020, without a previous diagnosis of myocarditis or pericarditis or laboratory-confirmed SARS-CoV-2 infection. Exposures The 28-day acute risk periods following the second and third dose of BNT162b2 and mRNA-1273, respectively, in a homologous schedule defines the exposures of interest. Main Outcomes and Measures Cohort participants were followed until an inpatient diagnosis of myocarditis, loss to follow-up, or end of study (latest data availability in each country), whichever occurred first. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis, with associated 95% confidence intervals (CIs), according to vaccination status. Country-specific results were combined in meta-analyses. Results A total of 8.9 million residents were followed for 12,271,861 person-years. We identified 1533 cases of myocarditis. 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 a second homologous dose (IRR, 2.08 [95% CI, 1.31 to 3.33] and 8.89 [95% CI, 2.26 to 35.03], respectively). The corresponding incidence rates following the third dose of BNT162b2 and mRNA-1273 were 0.86 and 1.95, respectively, within 28 days of follow-up among 100,000 individuals. Conclusions and Relevance Our results suggest that a booster dose is associated with increased myocarditis risk in male adolescents and young male adults.

Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study (preprint)

ObjectivesTo evaluate the effects of the Omicron variant on the post-acute symptoms, four months after infection with SARS-CoV-2. DesignA nationwide questionnaire study. SettingDenmark. Participants44,004 individuals aged 15 years or older with either a SARS-CoV-2 RT-PCR positive test result from the period of Delta dominance (July to November 2021), or a positive or negative RT-PCR test result from the period of Omicron dominance (December 2021 to January 2022). MethodsA questionnaire based cohort study with outcomes on post-acute physical, fatigue, cognitive, mental health symptoms, and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing cases and controls during the Omicron period, cases during the Delta and Omicron periods, and vaccinated cases with two and three doses during the Omicron period, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation and vaccination status. ResultsFour months after testing for SARS-CoV-2 during the Omicron period, cases experienced higher risk of 18 out of 26 post-acute symptoms and five out of five new-onset general health problems, compared to controls. Cases during the Omicron period experienced lower risks of 8 of the 18 symptoms and of all five new-onset general health problems, compared to Delta cases. The most prominent RDs estimated when comparing Omicron cases to controls were: memory issues (RD=5.4%, 95% CI 4.8 to 6.1), post-exertional malaise (RD=5.3%, 95% CI 3.1 to 7.7), fatigue/exhaustion (RD=5.2%, 95% CI 3.7 to 6.9), substantial fatigue (RD=5.0%, 95% CI 2.7 to 7.5), and dyspnea (RD=4.8%, 95% CI 3.8 to 5.9). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute altered/reduced sense of smell (dysosmia) (RD=-15.1%, 95% CI -17.0 to -12.9) and -taste (dysgeusia) (RD=-11.6%, 95% CI -13.6 to -9.7). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13 of the 26 post-acute symptoms and of three of the five new-onset general health problems, compared to those vaccinated with two doses. ConclusionsA considerable amount of cases infected during the Omicron period experienced post-acute symptoms and new-onset health problems, four months after testing, although milder compared to Delta cases. During the Omicron period, a booster vaccination dose was associated with fewer post-acute symptoms and new-onset health problems, four months after infection, compared to two doses of COVID-19 vaccine.

Post-acute symptoms, new onset diagnoses and health problems 6 to 12 months after SARS-CoV-2 infection: a nationwide questionnaire study in the adult Danish population (preprint)

Background. A considerable number of individuals infected with SARS-CoV-2 continue to experience symptoms after the acute phase. More information on duration and prevalence of these symptoms in non-hospitalized populations is needed. Methods. We conducted a nationwide cross-sectional study including 152 880 individuals aged 15-years or older, consisting of RT-PCR confirmed SARS-CoV-2 cases between September 2020-April 2021 (N=61 002) and a corresponding test-negative control group (N=91 878). Data were collected 6, 9 or 12 months after the test using web-based questionnaires. The questionnaire covered acute and post-acute symptoms, selected diagnoses, sick leave and general health, together with demographics and life style at baseline. Risk differences (RDs) between test-positives and -negatives were reported, adjusted for age, sex, single comorbidities, Charlson comorbidity score, obesity and healthcare-occupation. Findings. Six to twelve months after the test date, the risks of 18 out of 21 physical symptoms were elevated among test-positives and one third (29.6%) of the test-positives experienced at least one physical post-acute symptom. The largest risk differences were observed for dysosmia (RD = 10.92%, 95%CI 10.68-11.21%), dysgeusia (RD=8.68%, 95%CI 8.43-8.93%), fatigue/exhaustion (RD=8.43%, 95%CI 8.14-8.74%), dyspnea (RD=4.87%, 95%CI 4.65-5.09%) and reduced strength in arms/legs (RD=4.68%, 95%CI 4.45-4.89%). More than half (53.1%) of test-positives reported at least one of the following conditions: concentration difficulties (RD=28.34%, 95%CI 27.34-28.78%), memory issues (RD=27.25%, 95%CI 26.80-27.71%), sleep problems (RD=17.27%, 95%CI 16.81-17.73%), mental (RD=32.58%, 95%CI 32.11-33.09%) or physical exhaustion (RD=40.45%, 95%CI 33.99-40.97%), compared to 11.5% of test-negatives. New diagnoses of anxiety (RD=1.15%, 95%CI 0.95-1.34%) or depression (RD=1.00%, 95%CI 0.81-1.19%) were also more common among test-positives. Interpretation. At the population-level, where the majority of test-positives (96.0%) were not hospitalized during acute infection, a considerable proportion experience post-acute symptoms and sequelae 6-12 months after infection. Funding. None