Introduction The substantial burden of cardiovascular diseases highlights the urgent need for cost-effective interventions. Existing evidence on the cardioprotective effect of the influenza vaccine come primarily from populations with cardiovascular comorbidities, and remain susceptible to several sources of bias, including immortal time bias and unmeasured confounding.

Aims To assess the effect of influenza vaccination on cardiovascular events in a general older population in China while attenuating these limitations.

Methods This is a sequentially-designed, propensity score (PS) matched, vaccine effectiveness study under a target trial emulation framework. We used data from the Yinzhou Regional Health Care Database and included older residents of Yinzhou, China. We employed a sequential trial approach in which participants were categorized as influenza vaccinees or non-vaccinees based on their vaccination regimen during the one-week enrollment period of each sequential trial from 2020 to 2022. The outcomes of interest were major adverse cardiovascular events (MACE) and acute coronary syndromes (ACS) within one year of follow-up. To address measured and unmeasured confounding, PS matching was performed in conjunction with proximal causal inference using a two-stage Poisson regression to estimate incidence rate ratios (IRRs).

Results A total of 8,181,638 older adults were included across the 50 emulated trials. Of these, 170,011 were vaccinated against influenza, while 8,011,627 remained unvaccinated. After PS matching, all measured characteristics were well-balanced. In conjunction with the PCI approach, we found influenza vaccination was associated with decreased one-year risk of MACE (IRR: 0.86 [95% CI: 0.83-0.89]) and ACS (IRR: 0.87 [95% CI: 0.83-0.91]) compared to non-vaccination. Results were consistent across various subgroup and sensitivity analyses.

Conclusions Influenza vaccination may reduce the risk of MACE and ACS among older adults. Our findings further support influenza vaccination as an effective public health strategy for reducing cardiovascular disease burden.

Keywords Influenza vaccination; Cardiovascular diseases; Proximal causal inference

Introduction: Pneumonia is one of the leading causes of death among older adults. The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been demonstrated, including in Asian populations. However, limited evidence exists regarding its safety in relation to adverse events among older adults in Japan.

Aims: This study aimed to examine the association between PPSV23 vaccination and adverse events among Japanese older adults. This population-based analysis also sought to generate evidence on the safety of PPSV23 to promote informed public health decision-making.

Methods: This self-controlled risk interval study utilized an administrative claims database linked to the PPSV23 vaccination registry from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study in Japan from January 2016 to March 2023, including adults aged 65 years or older who received PPSV23. We evaluated the risk of myocarditis or pericarditis, Bell palsy, and thrombocytopenia in inpatient settings. A conditional Poisson regression model was applied to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). The risk and control periods were defined as days 1–28 and 57–112 after PPSV23 vaccination, respectively.

Results: Among 138,283 older adults who received PPSV23, the median age was 75 years (25th–75th percentile: 70–80), and 61.7% were women. No meaningful associations were found for myocarditis or pericarditis (IRR: 0.50; 95% CI: 0.06-4.47), Bell palsy (IRR: 1.11; 95% CI: 0.37-3.32), or thrombocytopenia (IRR: 1.00; 95% CI: 0.55-1.81).

Conclusions: In this large, registry-linked analysis, the elevated risks associated with PPSV23 vaccination for myocarditis or pericarditis, Bell palsy, or thrombocytopenia were not evident among older adults in Japan. Further studies evaluating the safety of PPSV23 against a broader range of adverse events, including cardiovascular, neurological, and immunological outcomes, are warranted to support vaccine safety awareness among Japanese older adults.

Keywords: Vaccine safety, older adults, self-controlled risk interval analysis

Introduction: Antibiotics, through their impact on the gut microbiota, have raised concerns about their potential to trigger disease activity in patients with inflammatory bowel disease (IBD).
Arms: This study aimed to evaluate the association between antibiotic use and the risk of IBD flare-ups, and to examine whether route of administration, antimicrobial spectrum, and antibiotic class modify this risk.
Methods: We conducted a self-controlled case series study using territory-wide electronic medical records from Hong Kong. We included adults with IBD who experienced at least one flare-up and received at least one course of antibiotics for infections outside the gastrointestinal (GI) tract between 2000 and 2024, to reduce indication bias related to gastrointestinal symptoms. Conditional Poisson regression models were used to estimate incidence rate ratios (IRRs) by comparing predefined risk periods to the baseline period. Subgroup analyses were conducted by route of administration, spectrum, and class.
Results: A total of 664 patients were included (median age: 46.7 years). The incidence of IBD flare was elevated during the month preceding antibiotic use (IRR 2.97), increased further during treatment (IRR 3.74), peaked within two weeks after the prescription ended (IRR 4.76), and returned to baseline between six weeks and six months after the prescription ended, versus baseline. Increased incidences were observed for oral antibiotics during and in two weeks after treatment (IRRs 4.53 and 3.86), but not for injectable antibiotics (interaction p-values <0.01). The IRRs for broad-spectrum antibiotics were higher than those for narrow-spectrum agents from one month before to six weeks after antibiotic use, versus baseline.
Conclusions: Antibiotic use for non-GI infections was associated with a short-term increase in IBD flare risk, predominantly with oral and broad-spectrum agents. When clinically appropriate, injectable or narrow-spectrum antibiotics may have a relatively smaller impact on IBD flare-ups.
Key words: Inflammatory bowel disease; antibiotics; flare-ups

Background: The association between COVID-19 vaccines and short-term risk of autoimmune diseases remain unclear, and there is limited evidence of different vaccine platforms.

Objective: We aim to evaluate the short-term risk of autoimmune diseases in individuals receiving COVID-19 vaccination (mRNA, adenovirus, protein).

Method: We conducted a self-controlled case series study using Taiwan’s National Health Insurance Research Database and the COVID-19 vaccination registry. We included individuals receiving at least one dose of an mRNA, adenovirus, or protein-based COVID-19 vaccine between 2021 and 2022. Moreover, we excluded patients with a history of autoimmune diseases. We included the first diagnosis of autoimmune disease during the study period. The post vaccination risk period was 21 days after each dose, the pre vaccination period was 14 days before each dose, overlapping days were defined as post vaccination, and all other time served as the reference period. The observation period ended on September 23, 2022, or at death, whichever occurs the first. Conditional Poisson regression was used to estimate the adjusted incidence rate ratio (aIRR), and time-varying factors were considered such as age and different SARS-CoV-2 variant periods. The aIRR was calculated for all doses combined and separately for each dose to evaluate dose-stratified effects.

Results: We identified 191,296 eligible patients with autoimmune diseases receiving at least one dose of COVID-19 vaccination. We observe an increased risk of new onset autoimmune disease within 21 days after any of the three COVID 19 vaccine platforms (mRNA: IRR 1.52, 95% CI 1.50–1.54; adenovirus: IRR 1.81, 95% CI 1.75–1.87; protein: IRR 1.82, 95% CI 1.72–1.92). In the dose stratified analysis, all three doses showed a consistent increased risk of autoimmune disease.

Conclusions: COVID-19 vaccination was associated with an increased short-term risk of autoimmune diseases across all platforms and doses.

Introduction: Few studies have reported the risk of clinical sequelae following COVID-19 infection in the Asia-Pacific region using multiregional data.

Aims: To obtain comprehensive evidence on the risk of clinical sequelae involving different organ systems over different time phases defined as short- (0-90 days), medium- (91-365 days) and long-term (after 365 days) period following COVID-19 infection using multi-regional databases from the Asia-Pacific regions.

Methods: A multi-regional retrospective cohort study was conducted using the electronic health records or claims data from five Asia Pacific regions, including Australia, New Zealand, Korea, Taiwan and Hong Kong. 1,169,866 individuals with COVID-19 infection and 2,553,944 comparators without infection were matched by propensity score and included in our study. Cox proportional regression was used to estimate the hazard ratio (HR) of various clinical sequelae, and all-cause mortality over short-, medium- and long-term phase following COVID-19 infection.

Results: Individuals with COVID-19 incurred a greater risk of all-cause mortality [Hazard ratio (HR) 12.78 (95%CI 3.65,44.72)] and clinical sequelae involving multiple organ systems over the short-term including respiratory [Interstitial Lung Disease: 6.01 (2.29,15.78)] and acute respiratory distress syndrome: 8.05 (5.08,12.74)] and cardiovascular disease: 1.89 (1.07, 3.33). The risk of clinical sequelae involving these organ systems largely subsided during the medium-term period [interstitial lung disease: 3.40 (1.11,10.46); all-cause mortality 2.42 (0.49, 11.87)] and long-term period [all-cause mortality 2.39 (0.33, 17.07)]. Patients aged over 65 years, or with a Charlson Comorbidity Index ≥4 have a higher risk of developing clinical sequelae compared to their respective counterparts.

Conclusions: From this multi-regional study among Asian-Pacific population, there is extensive short-term multi-organ involvement after COVID-19 infection. However, there is progressive reduction in the observed risk for most complications over the medium and long-term. The results were mainly consistent among all five Asian-Pacific regions included in our study.

Introduction: Post-COVID-19 syndrome (PCS) and post-COVID-19 vaccination syndrome (PCVS) present overlapping clinical features, potentially stemming from naturally acquired and vaccine-induced neutralising antibodies, respectively. The comparative long-term consequences of these conditions remain insufficiently characterised.
Aims: To systematically evaluate the prevalence of long-term consequences and quality of life (QoL) among individuals recovering from COVID-19 versus those receiving COVID-19 vaccination.
Methodology: A prospective cohort study enrolled 624 COVID-19-recovered and 407 COVID-19-vaccinated participants (without prior SARS-CoV-2 infection). Clinical manifestations (encompassing general, respiratory, cardiovascular, neurological, and digestive domains) and QoL (via EQ-5D-5L) were assessed at baseline, 6-, and 12-months following discharge or vaccination. Statistical analyses included calculation of odds ratios (OR) computed as COVID-recovered/COVID-19 vaccinated with 95% confidence intervals (CI) and significance testing (p-values).
Results: At baseline, COVID-19-recovered individuals exhibited a markedly higher prevalence of at least one long-term consequence (87.3% vs 52.8%, OR=0.162, CI 0.12–0.22). Although symptom prevalence declined over time, it remained elevated in the COVID-19-recovered group at 6 months (56.7% vs 39.8%, OR=0.546, CI 0.391–0.65) and 12 months (70.8% vs 58.5%, OR=0.58, CI 0.446–0.754). Fatigue, myalgia, and chest pain persisted at significantly higher rates among COVID-19-recovered individuals throughout all time points (p<0.05). Cognitive symptoms, including headache and impaired concentration, were also more prevalent at 12 months post-recovery (p<0.05). QoL scores were consistently lower in the COVID-19-recovered cohort compared to COVID-19-vaccinated individuals at baseline (0.85±0.05 vs 0.90±0.003, p < 0.001), 6 months (0.90±0.04 vs 0.93±0.06, p < 0.001), and 12 months (0.86±0.05 vs 0.88±0.06, p < 0.001).
Conclusions: Recovery from COVID-19 is associated with a significantly greater and more persistent symptom burden, as well as reduced QoL, compared to post-vaccination status. These findings underscore the necessity for ongoing surveillance and targeted interventions in COVID-19-recovered individuals.
Keywords: COVID-19 recovery, COVID-19 vaccination, Post-COVID-19 syndrome (PCS) and post-COVID-19 vaccination syndrome (PCVS), Long-term consequences, Quality of life