A Nationwide Survey of mRNA COVID-19 Vaccinee's Experiences on Adverse Events and Its Associated Factors.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccines have been distributed worldwide under emergency use authorization, the real-world safety profiles of mRNA vaccines still need to be clearly defined. We aimed to identify the overall incidence and factors associated with adverse events (AEs) following mRNA COVID-19 vaccination. METHODS: We conducted web-based survey from December 2 to 10 in 2021 with a 2,849 nationwide sampled panel. Study participants were individuals who had elapsed at least two-weeks after completing two dosing schedules of COVID-19 vaccination aged between 18-49 years. We weighted the participants to represent the Korean population. The outcome was the overall incidence of AEs following mRNA COVID-19 vaccination and associated factors. We estimated the weighted odds ratios (ORs) using multivariable logistic regression models to identify the factors associated with AEs. RESULTS: Of the 2,849 participants (median [interquartile range] age, 35 [27-42] years; 51.6% male), 90.8% (n = 2,582) for the first dose and 88.7% (n = 2,849) for the second dose reported AEs, and 3.3% and 4.3% reported severe AEs, respectively. Occurrence of AEs was more prevalent in mRNA-1273 (OR, 2.06; 95% confidence interval [CI], 1.59-2.67 vs. BNT162b2), female sex (1.88; 1.52-2.32), and those with dermatologic diseases (2.51; 1.32-4.77). History of serious allergic reactions (1.96; 1.06-3.64) and anticoagulant medication use (4.72; 1.92-11.6) were associated with severe AEs. CONCLUSION: Approximately 90% of participants reported AEs following mRNA COVID-19 vaccination. Substantial factors, including vaccine type (mRNA-1273), female sex, and dermatologic diseases were associated with AEs. Our findings could aid policymakers in establishing vaccination strategies tailored to those potentially susceptible to AEs.

Barriers to COVID-19 vaccine surveillance: the issue of under-reporting adverse events.

Objectives: This study investigated the reporting rates of adverse events following immunization (AEFIs) to the spontaneous reporting system (SRS) and its predictors among individuals with AEFIs after coronavirus disease 2019 (COVID-19) vaccination. Methods: A cross-sectional, web-based survey was conducted from December 2 to 20, 2021, recruiting participants >14 days after completion of a primary COVID-19 vaccination series. Reporting rates were calculated by dividing the number of participants who reported AEFIs to the SRS by the total number of participants who experienced AEFIs. We estimated adjusted odds ratios (AORs) using multivariate logistic regression to determine factors associated with spontaneous AEFI reporting. Results: Among 2,993 participants, 90.9% and 88.7% experienced AEFIs after the first and second vaccine doses, respectively (reporting rates, 11.6% and 12.7%). Furthermore, 3.3% and 4.2% suffered moderate to severe AEFIs, respectively (reporting rates, 50.5% and 50.0%). Spontaneous reporting was more prevalent in women (AOR=1.54; 95% CI, 1.31-1.81); those with moderate to severe AEFIs (AOR=5.47; 95% CI, 4.45-6.73), comorbidities (AOR=1.31; 95% CI, 1.09-1.57), a history of severe allergic reactions (AOR=2.02; 95% CI, 1.47-2.77); and those who had received mRNA-1273 (AOR=1.25; 95% CI, 1.05-1.49) or ChAdOx1 (AOR=1.62; 95% CI, 1.15-2.30) vaccines versus BNT162b2. Reporting was less likely in older individuals (AOR=0.98; 95% CI, 0.98-0.99 per 1-year age increment). Conclusion: Spontaneous reporting of AEFIs after COVID-19 vaccination was associated with younger age, female sex, moderate to severe AEFIs, comorbidities, history of allergic reactions, and vaccine type. AEFI under-reporting should be considered when delivering information to the community and in public health decision-making.

Risk of breakthrough SARS-CoV-2 infection and clinical outcomes among vaccinated patients with type 2 diabetes.

AIM: To explore the risk of breakthrough infection among patients with type 2 diabetes (T2D) and risk of severe clinical outcomes after SARS-CoV-2 infection according to vaccination status. MATERIALS AND METHODS: We conducted a population-based cohort study using South Korea's linked database of nationwide COVID-19 registry and claims data between 2018 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breakthrough infections were measured in 1:1 propensity-score (PS)-matched fully vaccinated patients with versus without T2D (full-vaccination cohort), and HRs for all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) use, and hospitalizations after SARS-CoV-2 infection were measured in 1:1 PS-matched T2D patients with versus without full-vaccination (T2D cohort). RESULTS: After 1:1 PS matching, 2 109 970 patients with and without T2D were identified (age 63.5 years; 50.9% male). Patients with T2D showed an increased risk of breakthrough infections compared to those without T2D (HR 1.10, 95% CI 1.06-1.14). The increased risk of breakthrough infections was more notable among T2D patients receiving insulin treatment. However, the risk of severe COVID-19 outcomes was lower in fully vaccinated T2D patients compared with unvaccinated T2D patients (all-cause mortality: HR 0.54, 95% CI 0.43-0.67; ICU admission/MV use: HR 0.31, 95% CI 0.23-0.41; hospitalization: HR 0.73, 95% CI 0.68-0.78). CONCLUSIONS: While patients with T2D remain a vulnerable population to SARS-CoV-2 infection even after full-vaccination, full-vaccination was associated with a lower risk of adverse clinical outcomes after SARS-CoV-2 infection. These findings support the guidelines recommending patients with T2D as a priority vaccination group.

Predictors of COVID-19 booster vaccine hesitancy among fully vaccinated adults in South Korea: a nationwide cross-sectional survey.

Objectives: To explore predictors of COVID-19 booster hesitancy among fully vaccinated young adults and parental factors on COVID-19 vaccine hesitancy for their children. Methods: A cross-sectional study was conducted via an online survey from December 2 to 20, 2021. We enrolled participants aged 18-49 years and elapsed ≥2 weeks after completing a primary series of COVID-19 vaccination. We estimated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regressions to evaluate factors associated with booster/vaccine hesitancy. Results: Among 2,993 participants, 48.8% indicated hesitancy (wait and see: 40.2%; definitely not: 8.7%). The booster hesitancy was more in females (OR 1.25, 95% CI 1.05-1.50), younger age group (1.44 [1.17-1.77] at 18-29 years vs. 40-49 years), lower education level (2.05 [1.10-3.82] in no high school vs. graduate degree), mRNA-1273 (2.01, 1.65-2.45 vs. BNT162b2), and those with serious adverse events following previous COVID-19 vaccination (2.03, 1.47-2.80). The main reasons for booster hesitancy were concerns about its safety (54.1%), followed by doubt about the efficacy (29.8%). Among 1,020 respondents who had children aged <18 years, 65.8% indicated COVID-19 vaccine hesitancy for their children; the hesitancy for children was higher at the younger age, and lower at lower education level, ChAdOx1 (vs. BNT162b2), and those with history of COVID-19 infection. Conclusion: Concerns on the efficacy and safety of COVID-19 vaccines were the major barrier to booster hesitancy. The initial COVID-19 vaccine type, younger age, women, lower education level, and adverse events following COVID-19 vaccine were the key predictors of booster hesitancy.

Challenges in evaluating treatments for COVID-19: The case of in-hospital anticoagulant use and the risk of adverse outcomes.

Anticoagulants are a potential treatment for the thrombotic complications resulting from COVID-19. We aimed to determine the association between anticoagulant use and adverse outcomes among hospitalized patients with COVID-19. We used data from the COVID-19 International Collaborative Research Project in South Korea from January to June 2020. We defined exposure using an intention-to-treat approach, with person-time classified as use or non-use of anticoagulants at cohort entry, and a time-varying approach. The primary outcome was all-cause, in-hospital mortality; the secondary outcome was a composite including respiratory outcomes, cardiovascular outcomes, venous thromboembolism, major bleeding, and intensive care unit admission. Cox proportional hazards models estimated adjusted hazard ratios (HRs) of the outcomes comparing use versus non-use of anticoagulants. Our cohort included 2,677 hospitalized COVID-19 patients, of whom 24 received anticoagulants at cohort entry. Users were older and had more comorbidities. The crude incidence rate (per 1,000 person-days) of mortality was 5.83 (95% CI: 2.80, 10.72) among anticoagulant users and 1.36 (95% CI: 1.14, 1.59) for non-users. Crude rates of the composite outcome were 3.20 (95% CI: 1.04, 7.47) and 1.80 (95% CI: 1.54, 2.08), respectively. Adjusted HRs for mortality (HR: 1.12, 95% CI: 0.48, 2.64) and the composite outcome (HR: 0.79, 95% CI: 0.28, 2.18) were inconclusive. Although our study was not able to draw conclusions on anticoagulant effectiveness for COVID-19 outcomes, these results can contribute to future knowledge syntheses of this important question. Our study demonstrated that the dynamic pandemic environment may have important implications for observational studies of COVID-19 treatment effectiveness.

Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. METHODS: We conducted a cohort study using South Korea's nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. RESULTS: Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13-2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96-2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49-4.14). CONCLUSIONS: While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.

Suitability of databases in the Asia-Pacific for collaborative monitoring of vaccine safety.

INTRODUCTION: Information regarding availability of electronic healthcare databases in the Asia-Pacific region is critical for planning vaccine safety assessments particularly, as COVID-19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE). METHODS: Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9-item introductory survey and a 51-item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research. RESULTS: Eleven databases containing vaccine-specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access. CONCLUSIONS: Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia-Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region.

Socioeconomic disparities in Korea by health insurance type during the COVID-19 pandemic: a nationwide study.

OBJECTIVES: This study explored socioeconomic disparities in Korea using health insurance type as a proxy during the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a retrospective cohort study using Korea's nationwide healthcare database, which contained all individuals who received a diagnostic test for COVID-19 (n=232,390) as of May 15, 2020. We classified our cohort by health insurance type into beneficiaries of the National Health Insurance (NHI) or Medicaid programs. Our study outcomes were infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19-related outcomes, a composite of all-cause death, intensive care unit admission, and mechanical ventilation use. We estimated age-, sex-, and Charlson comorbidity index score-adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using a multivariable logistic regression analysis. RESULTS: Of the 218,070 NHI and 14,320 Medicaid beneficiaries who received COVID-19 tests, 7,777 and 738 tested positive, respectively. The Medicaid beneficiaries were older (mean age, 57.5 vs. 47.8 years), more likely to be males (47.2 vs. 40.2%), and had a higher comorbidity burden (mean CCI, 2.0 vs. 1.7) than NHI beneficiaries. Compared to NHI beneficiaries, Medicaid beneficiaries had a 22% increased risk of SARS-CoV-2 infection (aOR, 1.22; 95% CI, 1.09 to 1.38), but had no significantly elevated risk of COVID-19-related outcomes (aOR 1.10, 95% CI 0.77 to 1.57); the individual events of the composite outcome yielded similar findings. CONCLUSIONS: As socioeconomic factors, with health insurance as a proxy, could serve as determinants during the current pandemic, pre-emptive support is needed for high-risk groups to slow its spread.

Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study.

OBJECTIVES: Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. METHODS: From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. RESULTS: Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). CONCLUSIONS: We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.

Association of mental disorders with SARS-CoV-2 infection and severe health outcomes: nationwide cohort study.

BACKGROUND: Epidemiological data on the association between mental disorders and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity are limited. AIMS: To evaluate the association between mental disorders and the risk of SARS-CoV-2 infection and severe outcomes following COVID-19. METHOD: We performed a cohort study using the Korean COVID-19 patient database based on national health insurance data. Each person with a mental or behavioural disorder (diagnosed during the 6 months prior to their first SARS-CoV-2 test) was matched by age, gender and Charlson Comorbidity Index with up to four people without mental disorders. SARS-CoV-2-positivity risk and the risk of death or severe events (intensive care unit admission, use of mechanical ventilation and acute respiratory distress syndrome) post-infection were calculated using conditional logistic regression analysis. RESULTS: Among 230 565 people tested for SARS-CoV-2, 33 653 (14.6%) had mental disorders; 928/33 653 (2.76%) tested SARS-CoV-2 positive and 56/928 (6.03%) died. In multivariable analysis using the matched cohort, there was no association between mental disorders and SARS-CoV-2-positivity risk (odds ratio OR = 0.95; 95% CI 0.87-1.04); however, a higher risk was associated with schizophrenia-related disorders (OR = 1.50; 95% CI 1.14-1.99). Among confirmed COVID-19 patients, the mortality risk was significantly higher in patients with than in those without mental disorders (OR = 1.99, 95% CI 1.15-3.43). CONCLUSIONS: Mental disorders are likely contributing factors to mortality following COVID-19. Although the infection risk was not higher for people with mental disorders overall, those with schizophrenia-related disorders were more vulnerable to infection.