Establishment of Safety Monitoring System for Vaccines Not Included in the National Immunization Program in Korea.

BACKGROUND: In Korea, there are no surveillance programs for vaccines that are not included in the national immunization program (NIP), and vaccine safety monitoring in the adult population is inadequate. This study aimed to establish a safety monitoring system for non-NIP vaccines in adults. METHODS: Frequently administered non-NIP vaccines were selected. Individuals were included if they received at least one of the selected vaccines at a participating institution and provided informed consent. Solicited and unsolicited adverse events were monitored using questionnaires sent through text messages on days 1, 3, 7, 28, and 90 post-vaccination. Selected adverse events of special interest (AESIs) were monitored monthly by retrospective review of electronic medical records. Causality was assessed according to the Korea Disease Control and Prevention Agency guidelines. RESULTS: Four vaccines (tetanus-diphtheria-pertussis [Tdap], pneumococcal conjugate 13-valent [PCV13], live zoster vaccine [ZVL], and recombinant zoster vaccine [RZV]) were selected, and their safety profiles were monitored at four tertiary hospitals and 10 primary care clinics. The response rates of the questionnaires on post-vaccination days 1, 7, 28, and 90 were 99.2%, 93.6%, 81.0%, and 48.7%, respectively. Of 555 AESI identified over 10 months, 10 cases received one of the selected non-NIP vaccines within 90 days of the event. CONCLUSION: We are establishing the first safety monitoring system for selected non-NIP vaccines in Korea since September 2022 and report its progress as of July 2023. However, continuous government support is essential for its maintenance and improvement.

Interim Estimates of 2023-2024 Seasonal Influenza Vaccine Effectiveness Among Adults in Korea.

In the 2023-2024 season, the influenza epidemic in South Korea peaked earlier than in recent years. In this study, we aimed to estimate the interim vaccine effectiveness (VE) of the influenza vaccination to prevent influenza during the early season. From November 1, 2023, to December 31, 2023, we enrolled 2,632 subjects with influenza-like illness from eight hospitals participating in hospital-based influenza morbidity and mortality surveillance. A retrospective test-negative case-control study was conducted to estimate the VE. The results showed an adjusted VE of 22.5% (95% confidence interval [CI], 6.6 to 35.8) for the total population. The adjusted VE was 22.3% (95% CI, 6.1 to 35.7) for influenza A and 9.4% (95% CI, -51.3 to 45.7) for influenza A/H1N1. Full results of the analysis will be reported.

Effectiveness of Bivalent mRNA Booster Vaccine Against COVID-19 in Korea.

BACKGROUND: Bivalent booster mRNA vaccines containing the omicron-variant strains have been introduced worldwide in the autumn of 2022. Nevertheless, the omicron subvariants evoked another large coronavirus disease 2019 (COVID-19) pandemic wave in late 2022 and early 2023. METHODS: A retrospective, test-negative, case-control study was conducted to estimate the vaccine effectiveness (VE) of bivalent COVID-19 vaccines in 8 university hospitals between January and February 2023. The case and control groups were divided based on nasopharyngeal COVID-19 real-time polymerase chain reaction results and matched based on age, sex, hospital, and date (week) of the test performed. The VE of the BA.1- or BA.4/BA.5-based mRNA vaccines were estimated. VE was calculated using the 1-adjusted odds ratio from multivariable logistic regression. RESULTS: In total, 949 patients and 947 controls were enrolled in this study. VE for the BA.4/BA.5-based bivalent mRNA vaccine was 43% (95% confidence interval [CI], 17, 61%). In subgroup analysis based on age and underlying medical conditions, BA.4/BA.5-based bivalent mRNA vaccine was effective against old adults aged ≥ 65-years (VE, 55%; 95% CI, 23, 73%) and individuals with comorbidities (VE, 54%; 95% CI, 23, 73%). In comparison, the BA.1-based bivalent mRNA vaccine did not demonstrate statistically significant effectiveness (VE, 25%; 95% CI, -8, 49%). CONCLUSION: The BA.4/BA.5-based bivalent mRNA booster vaccine provided significant protection against COVID-19 in the Korean adults, especially in the older adults aged ≥ 65 years and in individuals with underlying medical conditions.

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.

Concurrent Subacute Thyroiditis and Graves' Disease After COVID-19: A Case Report.

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves' disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Community-Acquired Pneumococcal Pneumonia in Highly Vaccinated Population: Analysis by Serotypes, Vaccination Status, and Underlying Medical Conditions.

BACKGROUND: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. METHODS: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. RESULTS: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). CONCLUSION: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.

Incidence and Healthcare Burden of Pertussis among Older Adults with and without Pre-Existing Chronic Obstructive Pulmonary Disease or Asthma in South Korea.

A retrospective cohort study was conducted to examine trends in the incidence and burden of pertussis among adults ≥50 years in South Korea, with/without pre-existing chronic obstructive pulmonary disease (COPD) or asthma. The nationwide Health Insurance Review and Assessment Service (HIRA) database was used to identify patients ≥50 years diagnosed with pertussis (2009-2018). Mean annual incidence of pertussis per 100 000 persons and overall mean incidence rate ratios (IRR) were calculated for patients with pre-existing COPD or asthma versus those with neither. Incremental healthcare costs (all-cause and pertussis-related) and healthcare utilisation (number of outpatient visits, emergency room visits, and number and length of hospitalisations) up to 12 months after, compared to 3 months before pertussis diagnosis, were also measured for each group (matched on sex, age, and Charlson Comorbidity Index). Of 1011 pertussis cases, 175 had asthma, 96 had COPD (not mutually exclusive), and 796 had neither. Overall mean pertussis incidence was 2.5, 3.4, and 0.5 for adults with pre-existing COPD, asthma, and those with neither. IRR (95% confidence interval) of pertussis for adults with pre-existing COPD and asthma was 4.9 (4.0-|6.1) and 6.7 (5.7-7.9). Both COPD-pertussis and asthma-pertussis groups had higher mean incremental all-cause costs and length of hospitalisations than the general-pertussis group 3 months following pertussis diagnosis. In conclusion, individuals ≥50 years in South Korea with pre-existing COPD or asthma were at an increased risk of being diagnosed with pertussis and had higher healthcare resource utilisation than those without these conditions.

Effectiveness of Pneumococcal Vaccination Against Pneumococcal Pneumonia Hospitalization in Older Adults: A Prospective, Test-Negative Study.

BACKGROUND: Despite use of the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) over the last decade, the disease burden of pneumococcal pneumonia is still high. We evaluated the field effectiveness of PCV13, PPSV23, and sequential vaccination against pneumococcal pneumonia in older adults. METHODS: This prospective multicenter study was conducted in adults aged ≥65 years hospitalized with community-acquired pneumonia (CAP) between September 2015 and August 2017. The case-control test-negative design was used to estimate vaccine effectiveness (VE) against pneumococcal CAP. RESULTS: Of 1525 cases with CAP hospitalization, 167 (11.0%) were identified as pneumococcal CAP. In the elderly aged ≥65 years, the adjusted VE of pneumococcal vaccines against pneumococcal CAP was statistically insignificant: 40.0% (95% confidence interval [CI], -10.8% to 67.5%) for PCV13 and 11.0% (95% CI, -26.4% to 37.3%) for PPSV23. However, in the younger subgroup (aged 65-74 years), sequential PCV13/PPSV23 vaccination showed the highest adjusted VE of 80.3% (95% CI, 15.9%-95.4%), followed by single-dose PCV13 (adjusted VE, 66.4% [95% CI, .8%-88.6%]) and PPSV23 (adjusted VE, 18.5% [95% CI, -38.6% to 52.0%]). CONCLUSIONS: Sequential PCV13/PPSV23 vaccination is most effective for preventing pneumococcal CAP among the elderly aged 65-74 years.

Duration of Humoral Immunity and Cross-Neutralizing Activity Against the Alpha, Beta, and Delta Variants After Wild-Type Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Prospective Cohort Study.

A prospective cohort study was conducted for adults with a diagnosis of with coronavirus disease 2019 (COVID-19). Convalescent blood samples were obtained 4, 6, and 11 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The seropositivity of anti-spike antibody was maintained in all patients (100%) until 11 months after COVID-19 diagnosis. Neutralizing antibody levels against wild-type SARS-CoV-2 gradually decreased but remained positive in >50% of patients 11 months after diagnosis: in 98.5% (67 of 68) at 4 months, 86.8% (46 of 53) at 6 months, and 58.8% (40 of 68) at 11 months. However, cross-neutralizing activity against the Beta and Delta variants was attenuated 2.53-fold and 2.93-fold, respectively, compared with the wild-type strain.

The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70.

BACKGROUND: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. METHODS: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. RESULTS: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. CONCLUSIONS: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

COVID-19 Vaccination in Korea: Past, Present, and the Way Forward.

Since its first emergence in late 2019, severe acute respiratory syndrome coronavirus-2 has claimed more than 6.5 million lives worldwide and continues to infect hundreds of thousands of people daily. To combat this once-in-a-century disaster, several vaccines have been developed at unprecedented speeds. Novel vaccine platforms (messenger ribonucleic acid vaccines and adenoviral vector vaccines) have played a major role in the current pandemic. In Korea, six vaccines, including a domestically developed recombinant vaccine, have been approved. As in other countries, vaccines have been proven to be safe and highly effective in Korea. However, rare serious adverse events and breakthrough infections have undermined public trust in the vaccines, even while the benefits of vaccination far outweigh the risks. The rise of the omicron variant and the subsequent increase in excess mortality demonstrated that while vaccines are a key component of the pandemic response, it alone can fail without non-pharmaceutical interventions like masking and social distancing. The pandemic of coronavirus disease has revealed both the strengths and weaknesses of our healthcare system and pandemic preparedness. When the next pandemic arrives, improved risk communication and vaccine development should be prioritized. To enable timely vaccine development, it is essential to make strategic and sufficient investments in vaccine research and development.

COVID-19 Vaccination Rates in Patients With Chronic Medical Conditions: A Nationwide Cross-Sectional Study.

As most individuals acquire immunity to severe acute respiratory syndrome coronavirus 2, South Korea declared a return to normalcy a few months ago. However, epidemic waves continue because of endlessly emerging variants and waning immunity. Health authorities are focusing on those at high risk of severe coronavirus disease 2019 to minimize damage to public health and the economy. In this regard, we investigated the vaccination rates in patients with various chronic medical conditions by examining the national health insurance claims data and the national immunization registry. We found that patients with chronic medical conditions, especially those of higher severity, such as malignancy, had vaccination rates approximately 10-20% lower than those of the general population. Public health authorities and healthcare providers should try to vaccinate these patients to avoid preventable morbidity and mortality.

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.

Relative Effectiveness of COVID-19 Vaccination in Healthcare Workers: 3-Dose Versus 2-Dose Vaccination.

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself.

Longitudinal Assessment of Antisevere Acute Respiratory Syndrome Coronavirus 2 Immune Responses for Six Months Based on the Clinical Severity of Coronavirus Disease 2019.

BACKGROUND: There is insufficient data on the longevity of immunity acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We aimed to evaluate the duration of SARS-CoV-2-specific humoral and cellular immunity according to the clinical severity of coronavirus disease 2019 (COVID-19). The study population comprised asymptomatic (n = 14), symptomatic/nonpneumonic (n = 42), and pneumonic (n = 41) patients. RESULTS: The anti-SARS-CoV-2 immunoglobulin class G and neutralizing antibody (NAb) titers lasted until 6 months after diagnosis, with positivity rates of 66.7% and 86.9%, respectively. Older age, prolonged viral shedding, and accompanying pneumonia were more frequently found in patients with sustained humoral immunity. Severe acute respiratory syndrome coronavirus 2-specific T-cell response was strongly observed in pneumonic patients and prominent in individuals with sustained humoral immunity. CONCLUSIONS: In conclusion, most (>85%) patients carry NAb until 6 months after diagnosis of SARS-CoV-2 infection, providing insights for establishing vaccination strategies against COVID-19.

Polyarthralgia and Myalgia Syndrome after ChAdOx1 nCOV-19 Vaccination.

Since February 26, 2021, when vaccination against coronavirus disease 2019 (COVID-19) began in South Korea, patients who visited the Korea University Guro Hospital with suspected adverse events after COVID-19 vaccination were monitored actively with interest. We encountered five unusual cases of polyarthralgia and myalgia syndrome in patients who received the ChAdOx1 nCOV-19 (AstraZeneca) vaccine. The patients (median age 67 years) were not previously diagnosed with arthropathy and rheumatologic diseases. They developed fever, myalgia, joint pain, and swelling three to seven days after vaccination. The symptoms persisted for up to 47 days despite antipyretic treatment. Arthralgia occurred in multiple joints, including small and large joints. A whole-body Technetium-99m methylene diphosphonate bone scan revealed unusual uptakes in the affected joints. Non-steroidal anti-inflammatory drugs with or without prednisolone relieved the symptoms of all patients. Further monitoring is required to clarify the long-term prognosis of this syndrome.

Developing a Framework for Pandemic COVID-19 Vaccine Allocation: a Modified Delphi Consensus Study in Korea.

BACKGROUND: This study presents a framework for determining the allocation and distribution of the limited amount of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: After analyzing the pandemic strategies of the major organizations and countries and with a literature review conducted by a core panel, a modified Delphi survey was administered to 13 experts in the fields of vaccination, infectious disease, and public health in the Republic of Korea. The following topics were discussed: 1) identifying the objectives of the vaccination strategy, 2) identifying allocation criteria, and 3) establishing a step-by-step vaccination framework and prioritization strategy based on the allocation criteria. Two rounds of surveys were conducted for each topic, with a structured questionnaire provided via e-mail in the first round. After analyzing the responses, a meeting with the experts was held to obtain consensus on how to prioritize the population groups. RESULTS: The first objective of the vaccination strategy was maintenance of the integrity of the healthcare system and critical infrastructure, followed by reduction of morbidity and mortality and reduction of community transmission. In the initial phase, older adult residents in care homes, high-risk health and social care workers, and personal support workers who work in direct contact with coronavirus disease 2019 (COVID-19) patients would be prioritized. Expansion of vaccine supply would allow immunization of older adults not included in phase 1, followed by healthcare workers not previously included and individuals with comorbidities. Further widespread vaccine supply would ensure availability to the extended adult age groups (50-64 years old), critical workers outside the health sector, residents who cannot socially distance, and, eventually, the remaining populations. CONCLUSION: This survey provides the much needed insight into the decision-making process for vaccine allocation at the national level. However, flexibility in adapting to strategies will be essential, as new information is constantly emerging.

Early Safety Monitoring of COVID-19 Vaccines in Healthcare Workers.

Hospital-based surveillance for adverse events was conducted on healthcare workers after they received the first dose of coronavirus disease 2019 (COVID-19) vaccine. Among the two new platform vaccines (messenger RNA- and adenoviral vector-based vaccines), the rates of systemic adverse events were significantly higher among adenovirus-vectored vaccine recipients. Fatigue (87.6% vs. 53.8%), myalgia (80.8% vs. 50.0%), headache (72.0% vs. 28.8%), and fever (≥ 38.0°C, 38.7% vs. 0%) were the most common adverse events among adenovirus-vectored vaccine recipients, but most symptoms resolved within 2 days. Both types of COVID-19 vaccines were generally safe, and serious adverse events rarely occurred.

Matrix Metalloproteinase-13 in Atherosclerotic Plaque Is Increased by Influenza A Virus Infection.

BACKGROUND: Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear. METHODS: We examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. RESULTS: We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.

Paradoxical long-term impact of maternal influenza infection on neonates and infants.

BACKGROUND: Pregnant women are at high risk of influenza-related morbidity and mortality. In addition, maternal influenza infection may lead to adverse birth outcomes. However, there is insufficient data on long-term impact of maternal influenza infection. METHODS: This study was conducted to assess the impact of maternal influenza infection on birth outcomes and long-term influence on infants by merging the Korea National Health Insurance (KNHI) claims database and National Health Screening Program for Infants and Children (NHSP-IC). Mother-offspring pairs were categorized by maternal influenza infection based on the ICD-10 code. RESULTS: Multivariate analysis revealed that maternal influenza infection significantly increased the risk of preterm birth (OR 1.408) and low birth weight (OR 1.198) irrespective of gestational age. The proportion of low birth weight neonates was significantly higher in influenza-infected women compared to those without influenza. However, since the fourth health screening (30-80 months after birth), the fraction of underweight was no longer different between children from influenza-infected and non-infected mothers, whereas the rates of overweight increased paradoxically in those born to mothers with influenza infection. CONCLUSIONS: Maternal influenza infection might have long-term effects on the health of children and adolescents even after infancy.