Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Duration of influenza vaccine effectiveness in the elderly in Japan: A retrospective cohort study using large-scale population-based registry data.

BACKGROUND: The immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness. METHODS: We used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases). RESULTS: We identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43-0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53-1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65-69 and 80-years, 5 months in 70-79 years. CONCLUSIONS: Our study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously.

Comparative effectiveness of BNT162b2 and mRNA-1273 booster dose after BNT162b2 primary vaccination against the Omicron variants: A retrospective cohort study using large-scale population-based registries in Japan.

BACKGROUND: Direct comparative effectiveness of booster doses of BNT162b2 and mRNA-1273 after BNT162b2 primary vaccination is unknown. METHODS: We investigated comparative effectiveness of BNT162b2 and mRNA-1273 booster dose using data from registry systems for vaccination and COVID-19 infection in a local city in Japan. We followed participants aged ≥16 years who completed the BNT162b2 primary vaccination between November 22, 2021, and April 15, 2022. We collected information on age, sex, vaccination status, vaccine type, and infection status. Age was categorized as 16-44, 45-64, 65-84, and ≥85 years. Vaccine effectiveness for mRNA-1273 and no booster vaccination against BNT162b2 was estimated using age-stratified Cox regression adjusted for age, sex, and days since the second vaccination. The estimated hazard ratios for mRNA-1273 and no booster vaccinations were integrated separately using random effects meta-analyses. RESULTS: During the study period, we identified 62,586 (40.4%), 51,490 (33.2%), and 40,849 (26.4%) participants who received BNT162b2, mRNA-1273, and no booster dose, respectively. The median age was 69, 71, and 47 years for BNT162b2, mRNA-1273, and no booster dose, respectively. The integrated hazard ratio with reference to BNT162b2 was 1.72 for no booster vaccination and 0.62 for mRNA-1273. The comparative effectiveness of mRNA-1273 was similar across age categories. CONCLUSIONS: Both homologous and heterologous vaccinations are effective against Omicron variants. In the head-to-head comparison, the effect was stronger in people who received heterologous vaccination than in those who received homologous vaccination. These findings may help improve logistics and decision making in future vaccination programs.

Intensive Care Unit versus High-Dependency Care Unit for COVID-19 Patients with Invasive Mechanical Ventilation.

RATIONALE: High-dependency care units (HDUs), also termed "intermediate care units," "step-down units," or "respiratory high-dependency units" are areas where patient care levels and costs are between those of the intensive care unit (ICU) and the general ward. In general, patients requiring mechanical ventilation are treated in the ICU rather than in the HDU, except for the use of HDU beds as surge capacity beds during a massive strain; however, the HDU as well as ICU are used as the standard care units for mechanically ventilated patients with coronavirus disease 2019 (COVID-19) in Japan. OBJECTIVES: To assess the outcomes of COVID-19 patients with invasive mechanical ventilation treated in the HDU versus those treated in the ICU. METHODS: In this retrospective cohort study, we used a multicenter inpatient database in Japan to identify mechanically ventilated patients with COVID-19 in the ICU or HDU on the start day of invasive mechanical ventilation from February 10, 2020 to November 30, 2021. The primary outcome was in-hospital mortality within 30 days from the start of the first invasive mechanical ventilation. Propensity score matching was performed to compare the outcomes of patients treated in the ICU with those treated in the HDU. RESULTS: Of 1,985 eligible COVID-19 patients with invasive mechanical ventilation, 1,303 (66%) were treated in the ICU and 682 (34%) were treated in the HDU on the start day of invasive mechanical ventilation. After propensity score matching, patients treated in the ICU had significantly lower in-hospital mortality within 30 days than those treated in the HDU (18.3% vs. 24.2%; risk difference, -5.8%; 95% confidence interval, -10.9% to -0.8%). CONCLUSIONS: This multicenter observational study in Japan suggests that care for mechanically ventilated COVID-19 patients in the ICU may significantly reduce in-hospital mortality within 30 days compared with care in the HDU. Establishing a critical care system that would allow COVID-19 patients requiring ventilators to be treated in the ICU is desirable. Because this study was an observational study, our finding represents an association, not a causation. Further studies of different critical care systems are warranted to confirm our findings.

A post-marketing safety assessment of COVID-19 mRNA vaccination for serious adverse outcomes using administrative claims data linked with vaccination registry in a city of Japan.

INTRODUCTION: The safety profiles of COVID-19 vaccines are incompletely evaluated in Japan. OBJECTIVES: To examine the risk of serious adverse effects after COVID-19 mRNA vaccination (BNT162b2 and mRNA-1273) in cohort studies and self-controlled case series (SCCS). METHODS: Using an administrative claims database linked with the COVID-19 vaccination registry in a city in Japan between September 2020 and September 2021, we identified health insurance enrolees aged ≥ 18 years. We evaluated the risk of acute myocardial infarction, appendicitis, Bell's palsy, convulsions/seizures, disseminated intravascular coagulation, immune thrombocytopenia, pulmonary embolism, haemorrhagic or ischemic stroke, venous thromboembolism, and all-cause mortality, 21 days following any COVID-19 mRNA vaccination, compared with non-vaccination periods. For the cohort studies, we estimated incidence rate ratios (IRRs) by Poisson regression and rate differences (IRDs) by weighted least-squares regression, adjusting for sex, age, and Charlson comorbidity index. We applied a modified SCCS design to appropriately treat outcome-dependent exposures. For the modified SCCS, we estimated within-subject IRRs by weighted conditional Poisson regression. Subgroup analyses stratified by sex and age were also conducted. RESULTS: We identified 184,491 enrolees [male: 87,218; mean (standard deviation) age: 64.2 (19.5) years] with 136,667 first and 127,322 s dose vaccinations. The risks of any outcomes did not increase in any analyses, except for the fact that the modified SCCS indicated an increased risk of pulmonary embolism after the first dose in women (within-subject IRR [95%CI]: 3.97 [1.18-13.32]). CONCLUSION: The findings suggested that the COVID-19 mRNA vaccine was generally safe, whilst a signal of pulmonary embolism following the first dose of the COVID-19 mRNA vaccine was observed.

Subacute Thyroiditis after COVID-19: A Literature Review.

Subacute thyroiditis (SAT), potentially caused by severe acute respiratory syndrome coronavirus 2 infection, has been reported as a complication of COVID-19 since 2020. The clinical characteristics and outcomes of SAT after COVID-19 remain incompletely defined. Therefore, we aimed to collect and survey case reports of SAT after COVID-19. We performed a systematic search of PubMed/MEDLINE, Web of Science, and Google Scholar. The keywords and MeSH terms used for the searches were "subacute thyroiditis" and "COVID-19." A total of 38 patients from 26 case reports, case series, and letters on SAT associated with COVID-19 were included and analyzed. The most frequent SAT symptom was neck pain (27 cases), followed by fever (22 cases). Of the 25 cases with information on the duration between onset of COVID-19 symptoms and onset of SAT symptoms, the shortest was simultaneous occurrence, and the longest was 4 months. In most cases, patients developed SAT at several days or weeks after the onset of COVID-19. All patients with SAT recovered with no severe complications or sequelae. Clinicians should be aware of the possibility of SAT development in patients with neck pain and fever following COVID-19. Further research is necessary to determine the relationship between SAT and COVID-19.