Comparative safety analysis of mRNA and adenoviral vector COVID-19 vaccines: a nationwide cohort study using an emulated target trial approach.

OBJECTIVE: This nationwide cohort study compared the incidence of adverse events of special interest (AESIs) between adenoviral vector-based (ChAdOx1) and mRNA-based (BNT162b2 or mRNA-1273) coronavirus disease 2019 (COVID-19) vaccines. METHODS: A targeted trial emulation study was conducted using data from the National Health Insurance Service database. Vaccinees aged 18-85 years who had received at least one dose of ChAdOx1 or an mRNA-based vaccine were identified. The 42-day risks of AESIs were calculated. RESULTS: A total of 1 767 539 ChAdOx1 vaccinees were matched exactly with mRNA vaccinees according to their risk factors. The 42-day risks of adverse events were low (∼0 to 176 events per 100 000 persons in both vaccine groups), and the incidence rates of AESIs were comparable between the two platforms, except for a higher occurrence of acute cardiac injury (incidence rate ratio [IRR], 1.22; 95% CI, 1.10-1.35), myocarditis or pericarditis (IRR, 2.14; 95% CI, 1.14-4.04), and arrhythmia (IRR, 1.46; 95% CI, 1.24-1.71) in mRNA vaccinees. The incidence of Guillain-Barré syndrome (IRR, 0.20; 95% CI, 0.06-0.69), vasovagal syncope (IRR, 0.77; 95% CI, 0.62-0.97), radiculopathy (IRR = 0.59, 95% CI, 0.41-0.84), and aseptic arthritis (IRR, 0.81; 95% CI, 0.70-0.93) was significantly lower in mRNA-based vaccinees compared with ChAdOx1 vaccinees. DISCUSSION: A remarkable platform-dependent difference was observed in the safety profiles of COVID-19 vaccines, particularly for myocarditis or pericarditis and Guillain-Barré syndrome. However, the overall risk of AESIs was low for both vaccine platforms.

Herpes Zoster Reactivation After mRNA and Adenovirus-Vectored Coronavirus Disease 2019 Vaccination: Analysis of National Health Insurance Database.

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). METHODS: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

COVID-19 vaccine type-dependent differences in immunogenicity and inflammatory response: BNT162b2 and ChAdOx1 nCoV-19.

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1ß levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.

Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated. METHOD: This prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs. RESULTS: Fifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3-4 weeks, 55.7 ± 2.4 U/mL at 5-8 weeks, and 81.3 ± 2.5 U/mL at 10-12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5-8 weeks, and 124.4 ± 2.6 at 10-12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/106 peripheral blood mononuclear cell was 25.0 (5.0-29.2) at baseline, 60.0 (23.3-178.3) at 5-8 weeks, and 35.0 (13.3-71.7) at 10-12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1-2, and resolved within two days. CONCLUSION: Single-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5-8 weeks and rather decrease at 10-12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible.

The Practice Guideline for Vaccinating Korean Patients with Autoimmune Inflammatory Rheumatic Disease.

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

Complicated infective endocarditis: a case series.

BACKGROUND: Infective endocarditis is associated with not only cardiac complications but also neurologic, renal, musculoskeletal, and systemic complications related to the infection, such as embolization, metastatic infection, and mycotic aneurysm. CASE PRESENTATION: We report three cases (the first patient is Chinese and the other two are Koreans) of complicated infective endocarditis; two of the cases were associated with a mycotic aneurysm, and one case was associated with a splenic abscess. One case of a patient with prosthetic valve endocarditis was complicated by intracerebral hemorrhage caused by mycotic aneurysm rupture. A second case of a patient with right-sided valve endocarditis associated with a central catheter was complicated by an abdominal aortic mycotic aneurysm. The third patient had a splenic infarction and abscess associated with infected cardiac thrombi. CONCLUSIONS: Complicated infective endocarditis is rare and is associated with cardiac, neurologic, renal, musculoskeletal, and systemic complications related to infection, such as embolization, metastatic infection, and mycotic aneurysm. Infective endocarditis caused by Staphylococcus aureus is more frequently associated with complications. Because the mortality rate increases when complications develop, aggressive antibiotic therapy and surgery, combined with specific treatments for the complications, are necessary.

Do All Patients Require Prophylactic Drainage After Gastrectomy for Gastric Cancer? The Experience of a High-Volume Center.

BACKGROUND: Although our previous randomized controlled trial showed that there was no difference in postoperative complications after gastric cancer surgery between patients with and without a prophylactic drains (PDs), PDs are commonly used by most surgeons and at most institutions. However, these results have not yet been validated elsewhere. The purpose of this study was to analyze the incidence, characteristics, and risk factors for a postoperative percutaneous catheter drainage (PCD) procedure after gastric cancer surgery when PDs were not used. METHODS: We reviewed data from 1989 patients who underwent gastrectomy with lymphadenectomy for gastric cancer with curative intent from January 2012 to December 2013. RESULTS: The incidence of PCD in the abdomen was 1.8 % (22/1249) and 9.1 % (67/740) in patients with and without PD, respectively. In the without-PD group, age [odds ratio (OR) 1.032; p = 0.013], male gender (OR for female 0.38; p = 0.005), open surgery (OR for minimally invasive surgery 0.16; p = 0.013), and longer operative time (OR 1.01; p < 0.001) were independent risk factors for postoperative PCD in the abdomen. In the without-PD group, no microbes were detected in the peritoneal fluid obtained by PCD in 72.1 % (44/61) of patients who underwent PCD, and the most commonly identified organisms were Escherichia coli and Candida albicans. CONCLUSION: Not using a PD increased the risk of PCD postoperatively, but no microbes in peritoneal fluid were detected in the most patients. Selective use of PD in patients during gastric cancer surgery may be possible using our risk factor analysis.

Epidemiologic differences of four major respiratory viruses between children, adolescents, and adults in Korea.

The purpose of this study was to investigate the epidemiology of four major respiratory viruses among the Korean population. This retrospective study was conducted over four years, from January 2005 to December 2008. Among a total of 23,806 specimens, 5512 virus isolates underwent culture for influenza A and B viruses (IFA/B), parainfluenza virus (PIV), respiratory syncytial virus (RSV), and adenovirus (ADV). Patients were divided into two groups: children/adolescents and adults. The viruses detected in specimens from children/adolescents included PIV (7.8%), RSV (7.3%), ADV (4.0%), IFA (2.9%), and IFB (2.2%). In adults, IFB (5.6%), IFA (4.4%), RSV (1.1%), PIV (0.5%), and ADV (0.2%) were detected, thus demonstrating two distinct patterns of virus infection. Influenza viruses had similar seasonal patterns and periods of infection among children/adolescents and adults; however, the isolation rate in adults was slightly higher than that in children and adolescents. Correlation coefficient analysis based on weekly seasonal patterns indicated that influenza viruses were detected a week earlier in children than in adults. RSV, PIV, and ADV did not show similar trends between the two age groups due to low detection rates and sporadic isolations among adult patients. Of note, different respiratory viruses should be considered depending on patient age when a clinical respiratory viral infection is suspected. Furthermore, in the case of influenza, a preceding epidemic among a pediatric population could be useful to predict a subsequent epidemic among adults.

Etiology and clinical outcomes of acute respiratory virus infection in hospitalized adults.

BACKGROUND: Etiologies and clinical profiles of acute respiratory viral infections need to be clarified to improve preventive and therapeutic strategies. MATERIALS AND METHODS: A retrospective observational study at a single, university-affiliated center was performed to evaluate the respiratory viral infection etiologies in children compared to that in adults and to document the clinical features of common viral infections for adults from July 2009 to April 2012. RESULTS: The common viruses detected from children (2,800 total patients) were human rhinovirus (hRV) (31.8%), adenovirus (AdV) (19.2%), respiratory syncytial virus (RSV) A (17.4%), RSV B (11.7%), and human metapneumovirus (hMPV) (9.8%). In comparison, influenza virus A (IFA) had the highest isolation rate (28.5%), followed by hRV (15.5%), influenza virus B (IFB) (15.0%), and hMPV (14.0%), in adults (763 total patients). Multiple viruses were detected in single specimens from 22.4% of children and 2.0% of adults. IFA/IFB, RSV A/B, and hMPV exhibited strong seasonal detection and similar circulating patterns in children and adults. Adult patients showed different clinical manifestations according to causative viruses; nasal congestion and rhinorrhea were more common in hRV and human coronavirus (hCoV) infection. Patients with RSV B, hRV, or AdV tended to be younger, and those infected with RSV A and hMPV were likely to be older. Those with RSV A infection tended to stay longer in hospital, enter the intensive care unit more frequently, and have a fatal outcome more often. The bacterial co-detection rate was 26.5%, and those cases were more likely to have lower respiratory tract involvement (P = 0.001), longer hospital stay (P = 0.001), and higher mortality (P = 0.001). CONCLUSIONS: The etiologic virus of an acute respiratory infection can be cautiously inferred based on a patient's age and clinical features and concurrent epidemic data. Large-scale prospective surveillance studies are required to provide more accurate information about respiratory viral infection etiology, which could favorably influence clinical outcomes.