Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. METHODS: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. RESULTS: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03-13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26-14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). CONCLUSION: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine.

Background: Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide; however, the longevity of vaccine effectiveness is not known. Objective: We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. Methods: SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). Results: A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5-2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8-4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0-1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. Conclusions: The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine

Background Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide;however, the longevity of vaccine effectiveness is not known. Objective We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. Methods SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). Results A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5–2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8–4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0–1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. Conclusions The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Aseptic Meningitis Following Second Dose of an mRNA Coronavirus Disease 2019 Vaccine in a Healthy Male: Case Report and Literature Review.

Vaccines are one of the most important strategies against pandemics or epidemics involving infectious diseases. With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there have been global efforts for rapid development of coronavirus disease 2019 (COVID-19) vaccine and vaccination is being performed globally on a massive scale. With rapid increase in vaccination, rare adverse events have been reported. Well-known neurological adverse events associated with COVID-19 vaccination include Guillain-Barré syndrome, myelitis, and encephalitis. However, COVID-19 vaccine-related aseptic meningitis has rarely been reported. A 32-year-old healthy man visited our hospital with a complaint of headache for 1 week. He had received the second dose of the BNT162b2 mRNA COVID-19 vaccine 2 weeks before the onset of headache. Since the initial cerebrospinal fluid (CSF) profile suggested viral meningitis, we started treatment with an antiviral agent. However, the symptoms and follow-up CSF profile on day 7 of hospitalization showed no improvement and SARS-CoV-2 IgG antibodies were detected in the CSF. We suspected aseptic meningitis associated with the vaccination and intravenous methylprednisolone (500 mg/day) was administered for 3 days. The symptoms improved and the patient was discharged on day 12 of hospitalization.

Clinical Characteristics and Risk Factors for Severe Disease of Coronavirus Disease 2019 in a Low Case Fatality Rate Region in Korea.

BACKGROUND: Jeju island had the seventh highest incidence rate of coronavirus disease 2019 (COVID-19) but showed the lowest case fatality rate among 17 provinces of Korea, which may be associated with comorbidities and geographic differences. This study aimed to analyze the epidemiological and clinical characteristics of patients with COVID-19 and evaluate the risk factors for severe COVID-19 in Jeju island, Korea. MATERIALS AND METHODS: All patients with COVID-19 admitted between February 20, 2020, and June 19, 2021, at a single center were retrospectively enrolled in this study. The severity of illness was defined using five categories (asymptomatic, mild, moderate, severe, and critical) according to the National Institute of Health criteria. Then, patients with severe and critical illness were grouped into a severe group, whereas patients with asymptomatic, mild, and moderate illness were grouped into a non-severe group. Multivariate logistic regression analysis was performed using risk factors that were found to be significantly associated with the severe group. RESULTS: This study included 348 patients with a median age was 57 years, and 37.5% were aged 60 or older. Among them, 43.4% were male and 10.9% were asymptomatic, whereas 41.4%, 33.9%, 12.9%, and 1.1% had mild, moderate, severe, and critical illness. The all-cause mortality of patients with COVID-19 was 0.28% (1/348). Among confirmed patients with COVID-19, exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was mainly within Jeju island (75.9%). The mean body mass index was 24.09 ± 4.04 kg/m², the median comorbidity index score was low in each group (0 in asymptomatic; 1 in mild; 1 in moderate; 1 in severe; and 2 in critical group, P <0.548). In the multivariable analysis, male sex [odds ratio (OR), 6.37; 95% confidence interval (CI), 2.69 - 15.13; P <0.001], ≥65 years of age (OR, 2.68; 95% CI, 1.18 - 6.10; P <0.019), chronic pulmonary disease (OR, 6.10; 95% CI, 1.40 - 26.61; P = 0.016), and length of fever duration (OR, 1.33; 95% CI, 1.19 - 1.49; P <0.001) were independently associated with severe COVID-19. CONCLUSION: The most relevant risk factors of COVID-19 severity were male sex, older age, underlying chronic lung diseases, and duration of fever during hospitalization. The risk factors for severe COVID-19 were not significantly different from those reported in other studies. However, a lower proportion of the older population among confirmed SARS-CoV-2 cases might contribute to the lower fatality rate than the national rate.