Immune Responses After Vaccination With Primary 2-Dose ChAdOx1 Plus a Booster of BNT162b2 or Vaccination With Primary 2-Dose BNT162b2 Plus a Booster of BNT162b2 and the Occurrence of Omicron Breakthrough Infection.

BACKGROUND: Before the omicron era, health care workers were usually vaccinated with either the primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus a booster dose of BNT162b2 (BBB group) in Korea. METHODS: The two groups were compared using quantification of the surrogate virus neutralization test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well as the omicron breakthrough infection cases. RESULTS: There were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group. Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower in the CCB (SVNT-WT [before-after]: 72.02-97.61%, SVNT-O: 15.18-42.29%) group than in the BBB group (SVNT-WT: 89.19-98.11%, SVNT-O: 23.58-68.56%; all P < 0.001). Although the median IgG concentrations were different between the CCB and BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively, P < 0.001), they were not different between the two groups after the booster vaccination (7.246 vs. 7.979 AU/mL, respectively, P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group than in the CCB group (550.5 and 387.5 mIU/mL, respectively, P = 0.014). There was also a difference in the cumulative incidence curves over time (CCB group 50.0% vs. BBB group 41.8%; P = 0.045), indicating that breakthrough infection occurred faster in the CCB group. CONCLUSION: The cellular and humoral immune responses were low in the CCB group so that the breakthrough infection occurred faster in the CCB group than in the BBB group.

A study on changes in lung function, neutralizing antibodies, and symptoms of adult patients hospitalized with COVID-19.

Background/Aims: To identify changes in symptoms and pulmonary sequelae in patients with coronavirus disease 2019 (COVID-19). Methods: Patients with COVID-19 hospitalized at seven university hospitals in Korea between February 2020 and February 2021 were enrolled, provided they had ≥ 1 outpatient follow-up visit. Between January 11 and March 9, 2021 (study period), residual symptom investigations, chest computed tomography (CT) scans, pulmonary function tests (PFT), and neutralizing antibody tests (NAb) were performed at the outpatient visit (cross-sectional design). Additionally, data from patients who already had follow-up outpatient visits before the study period were collected retrospectively. Results: Investigation of residual symptoms, chest CT scans, PFT, and NAb were performed in 84, 35, 31, and 27 patients, respectively. After 6 months, chest discomfort and dyspnea persisted in 26.7% (4/15) and 33.3% (5/15) patients, respectively, and 40.0% (6/15) and 26.7% (4/15) patients experienced financial loss and emotional distress, respectively. When the ratio of later CT score to previous ones was calculated for each patient between three different time intervals (1-14, 15-60, and 61-365 days), the median values were 0.65 (the second interval to the first), 0.39 (the third to the second), and 0.20 (the third to the first), indicating that CT score decreases with time. In the high-severity group, the ratio was lower than in the low-severity group. Conclusions: In COVID-19 survivors, chest CT score recovers over time, but recovery is slower in severely ill patients. Subjects complained of various ongoing symptoms and socioeconomic problems for several months after recovery.

Immune Responses against the Omicron Variant of SARS-CoV-2 after a Third Dose of COVID-19 Vaccine in Patients Living with Human Immunodeficiency Virus (PLWH): Comparison with Healthcare Workers.

We compared immune responses against the omicron variant of SARS-CoV-2 after a third dose of the coronavirus disease 2019 (COVID-19) vaccine between people living with human immunodeficiency (PLWH) and healthcare workers (HCWs). In this prospective observational study, PLWH and HCWs vaccinated with at least two doses of vaccine were enrolled. We analyzed neutralizing responses using the GenScript SARS-CoV-2 surrogate virus neutralization test kit. Twenty-nine PLWH and 114 HCWs were included to analyze immune responses after the third vaccination. Most PLWH (86.2%) had fully suppressed viral loads and CD4 T cell counts were well-controlled (median 670.0 cells/µL). The neutralizing responses against the omicron variant in PLWH were not significantly different from those in HCWs (43.94% vs. 51.77%, p = 0.42). However, neutralizing responses against the omicron variant were significantly impaired by about 50% compared with wild type SARS-CoV-2 in PLWH (43.94% vs. 97.46%, p < 0.001) and HCWs (51.77% vs. 97.74%, p < 0.001). Although neutralizing responses against the omicron variant in well-controlled PLWH were comparable to those of HCWs, the responses were much lower than those against wild type in both PLWH and HCWs. Therefore, the risk of breakthrough SARS-CoV-2 infection due to the currently circulating omicron variant is still high despite three doses of vaccine in PLWH and will not differ from HCWs.

Immunogenicity against the Omicron Variant after mRNA-Based COVID-19 Booster Vaccination in Medical Students Who Received Two Primary Doses of the mRNA-1273 Vaccine.

We evaluated the immune response against the Omicron variant after mRNA-based COVID-19 booster vaccination in medical students. We prospectively enrolled medical students who received two primary doses of the mRNA-1273 vaccine. The neutralizing response and the SARS-CoV-2-specific T-cell response was evaluated. A total of 56 serum samples were obtained before booster vaccination. Nineteen students (33.9%) developed COVID-19 two months after booster vaccination. Of 56 students, 35 students (12 infected and 23 uninfected) were available for blood sampling four months after booster vaccination. In comparison with uninfected students, infected students showed a significantly higher level of SARS-CoV-2-specific IgG (5.23 AU/mL vs. 5.12 AU/mL, p < 0.001) and rate of neutralizing response (96.22% vs. 27.18%, p < 0.001) four months after booster vaccination. There was no significant difference in the SARS-CoV-2-specific T-cell response. Among 23 infection-naive students, the neutralizing response was significantly higher in those who received the mRNA-1273 booster than in those who received the BNT162b2 booster (69.07% vs. 26.43%, p = 0.02). In our study, booster vaccination with mRNA-1273 instead of BNT162b2 was significantly associated with a higher neutralizing response.

Treatment delay and outcomes of ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention during the COVID-19 era in South Korea.

BACKGROUND/AIMS: Little is known about the clinical characteristics and treatment outcomes of ST-segment elevation myocardial infarction (STEMI) in Korea during the coronavirus disease 2019 (COVID-19) era. We aimed to evaluate the clinical characteristics and treatment outcomes of patients with STEMI in the COVID-19 era. METHODS: A total of 588 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were included in this study. The patients were categorized into the COVID-19 (from January 20, 2020 to December 31, 2020) and control groups (from January 20, 2019 to December 31, 2019). RESULTS: The COVID-19 group showed pre-hospital and in-hospital delays than the control group. The control group underwent more thrombus aspiration and had a higher proportion of left main coronary artery diseases, while the COVID-19 group had a higher proportion of multivessel diseases with a marked increase in the number and total length of stents than the control group. As for the prescribed medications, the COVID-19 group was administered more beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins than the control group. The clinical outcomes were comparable between the groups, except for higher incidences of atrioventricular block and temporary pacemaker implantation in the COVID-19 group. CONCLUSION: Reperfusion after STEMI treatment during the COVID-19 period was delayed; therefore, efforts should be made to improve on reperfusion.

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.

Relationship between SARS-CoV-2 antibody titer and the severity of COVID-19.

BACKGROUND: It remains unclear whether high titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies aggravate clinical manifestations in patients or whether severe clinical manifestations result in high antibody titers. Thus, we investigated the cause-effect relationship between SARS-CoV-2 antibody titers and disease severity. METHODS: We prospectively enrolled patients admitted with the diagnosis of coronavirus disease-19 (COVID-19) from February 2020 to August 2020. We measured SARS-CoV-2 antibody titers, namely anti-receptor-binding domain (RBD) antibody and neutralizing antibody (NAb), from blood samples and calculated the chest radiograph (CXR) scores of the patients to evaluate the severity of COVID-19. RESULTS: Overall, 40 patients with COVID-19 were enrolled. Pneumonia was observed in more than half of the patients (25/40, 60%). SARS-CoV-2 antibody titers were higher in patients who were aged >60 years (anti-RBD antibodies, P = 0.003 and NAb, P = 0.009), presented with pneumonia (P = 0.006 and 0.007, respectively), and required oxygen therapy (P = 0.003 and 0.004, respectively) than in those who were not. CXR scores peaked (at 15-21 days after the onset of symptoms) statistically significantly earlier than SARS-CoV-2 antibody titers (at 22-30 days for NAb and at 31-70 days for anti-RBD antibody). There was a close correlation between the maximum CXR score and the maximum SAR-CoV-2 antibody titer. CONCLUSIONS: Based on the comparison of the peak time of SARS-CoV-2 antibody titers with the CXR score after symptom onset, we suggest that severe clinical manifestations result in high titers of SARS-CoV-2 antibodies.

Case Report: Acute Fulminant Myocarditis and Cardiogenic Shock After Messenger RNA Coronavirus Disease 2019 Vaccination Requiring Extracorporeal Cardiopulmonary Resuscitation.

Recently, myocarditis following messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination has become an important social issue worldwide. According to the reports so far, myocarditis related to mRNA COVID-19 vaccination is rare and usually associated with a benign clinical course without intensive care or any sequelae of fulminant myocarditis. Here, we report a case of acute fulminant myocarditis and cardiogenic shock after the mRNA COVID-19 vaccination, requiring extracorporeal cardiopulmonary resuscitation. Clinicians should keep in mind the possibility of progression to fulminant myocarditis in patients who presented with suggestive symptoms or signs of myocarditis after the COVID-19 vaccination.

SARS-CoV-2-Specific Antibody and T Cell Response Kinetics According to Symptom Severity.

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.

Systemic Adverse Events and Use of Antipyretics Predict the Neutralizing Antibody Positivity Early after the First Dose of ChAdOx1 Coronavirus Disease Vaccine.

Vaccination is considered crucial for the eradication of the coronavirus disease (COVID-19). In our medical center in Korea, most health care workers (HCWs) were vaccinated with the ChAdOx1 COVID-19 vaccine. After vaccination, many HCWs complained of adverse events (AEs). However, it remains unclear whether the production of neutralizing antibodies (NAb) was affected. Therefore, here, we aimed to evaluate AEs and early NAb production in relatively healthy Asians who received the ChAdOx1 vaccine and determine the effect of AEs and antipyretics on early NAb production against COVID-19. Of the 182 Korean HCWs who received the first dose of ChAdOx1 vaccine, 172 (94.5%) experienced ≥1 adverse events and 148 (81.3%) tested positive for NAb 33-40 days after the vaccination. NAb-positive vaccine recipients reported systemic AEs and consumed acetaminophen more frequently than NAb-negative recipients. We identified an association between antibody response and COVID-19 vaccine-related AEs. In conclusion, most ChAdOx1 vaccine recipients reported AEs in our medical center.

Risk factors for isolation of multi-drug resistant organisms in coronavirus disease 2019 pneumonia: A multicenter study.

OBJECTIVES: Superimposed multi-drug resistant organisms (MDROs) co-infection can be associated with worse outcomes in patients with severe coronavirus disease 2019 (COVID-19), even if these patients were managed with strict airborne and contact precautions. Identifying risk factors for isolation of MDROs is critical to COVID-19 treatment. METHODS: All eligible adult patients with confirmed COVID-19 pneumonia from 10 hospitals in the Republic of Korea between February 2020 and May 2020 were retrospectively enrolled. Using this cohort, epidemiology and risk factors for isolation of MDROs were evaluated. RESULTS: Of 152 patients, 47 with microbial culture results were included. Twenty isolates of MDROs from 13 (28%) patients were cultured. Stenotrophomonas maltophilia (5 isolates) was the most common MDRO, followed by methicillin-resistant staphylococcus aureus (4 isolates). MDROs were mostly isolated from sputum samples (80%, 16/20). The median time from hospitalization to MDRO isolation was 28 days (interquartile range, 18-38 days). In-hospital mortality was higher in patients with MDRO isolation (62% vs 15%; P = .001). Use of systemic corticosteroids after diagnosis of COVID-19 (adjusted odds ratio [aOR]: 15.07; 95% confidence interval [CI]: 2.34-97.01; P = .004) and long-term care facility (LTCF) stay before diagnosis of COVID-19 (aOR: 6.09; 95% CI: 1.02-36.49; P = .048) were associated with MDRO isolation. CONCLUSIONS: MDROs were isolated from 28% of COVID-19 pneumonia patients with culture data and 8.6% of the entire cohort. Previous LTCF stay and adjunctive corticosteroid use were risk factors for the isolation of MDROs. Strict infection prevention strategies may be needed in these COVID-19 patients with risk factors.

Impact of social distancing on the spread of common respiratory viruses during the coronavirus disease outbreak.

During the coronavirus disease (COVID-19) pandemic, social distancing was effective in controlling disease spread across South Korea. The impact of national social distancing on the spread of common respiratory virus infections has rarely been investigated. We evaluated the weekly proportion of negative respiratory virus polymerase chain reaction (PCR) test results and weekly positive rates of each respiratory virus during the social distancing period (10th-41st weeks of 2020) and the corresponding period in different years, utilizing the national respiratory virus surveillance dataset reported by the Korean Center for Disease Control and Prevention. The proportions of negative respiratory virus PCR test results increased up to 87.8% and 86.1% during level 3 and level 2 of the social distancing period, respectively. The higher the level of social distancing, the higher the proportion of negative respiratory virus PCR test results. During the social distancing period, the mean weekly positive rates for parainfluenza virus, influenza virus, human coronavirus, and human metapneumovirus were significantly lower than those during the same period in 2015-2019 (0.1% vs. 9.3%, P <0.001; 0.1% vs. 7.2%, P <0.001; 0.4% vs. 2.3%, P <0.001; and 0.2% vs. 5.3%, P <0.001, respectively). The mean positive rate for rhinovirus/enterovirus during level 3 social distancing was lower than that in the same period in 2015-2019 (8.5% vs. 19.0%, P <0.001), but the rate during level 1 social distancing was higher than that in the same period in 2015-2019 (38.3% vs. 19.4%, P <0.001). The national application of social distancing reduced the spread of common respiratory virus infections during the COVID-19 pandemic.

Evaluation of rapid SARS-CoV-2 antigen tests, AFIAS COVID-19 Ag and ichroma COVID-19 Ag, with serial nasopharyngeal specimens from COVID-19 patients.

We evaluated the diagnostic accuracy of two newly developed, point-of-care, rapid antigen tests (RATs) for detecting SARS-CoV-2, the AFIAS COVID-19 Ag and the ichromaTM COVID-19 Ag, and investigated antigen kinetics. A total of 200 serially collected nasopharyngeal (NP) specimens from 38 COVID-19 patients and 122 specimens from negative controls were analyzed. Diagnostic sensitivity and specificity were assessed in comparison to molecular test results and subdivided according to targeted genes (E, RdRP, and N) and days post-symptom onset (PSO). For the kinetics evaluation, cut-off-indices from serial NP specimens were used according to the number of days PSO. Both RATs showed sensitivity of 91.3‒100% for specimens with cycle threshold (Ct) < 25. The specificity of AFIAS was 98.7‒98.9% and that of ichromaTM was 100.0%. The kappa values of AFIAS and ichromaTM for the molecular testing of specimens with Ct < 25 (RdRP) were 0.97 and 1.00, respectively. The sensitivity of AFIAS and ichromaTM for all genes was lower for specimens collected at 8‒14 PSO than for those collected before 7-days PSO. The kinetics profiles showed that antigen levels gradually decreased from ≤ 7-days PSO to > 22-days PSO. Both RATs showed excellent specificity and acceptable sensitivity for NP specimens with higher viral loads and for specimens collected within 7-days PSO. Hence, they have the potential to become useful tools for the early detection of SARS-CoV-2. However, because of concerns about false negativity, RATs should be used in conjunction with molecular tests.

Clinical and radiological findings of adult hospitalized patients with community-acquired pneumonia from SARS-CoV-2 and endemic human coronaviruses.

Endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are members of the family Coronaviridae. Comparing the findings of the infections caused by these viruses would help reveal the novel characteristics of SARS-CoV-2 and provide insight into the unique pathogenesis of SARS-CoV-2 infection. This study aimed to compare the clinical and radiological characteristics of SARS-CoV-2 and endemic HCoVs infection in adult hospitalized patients with community-acquired pneumonia (CAP). This study was performed at a university-affiliated tertiary hospital in the Republic of Korea, between January 1, 2015, and July 31, 2020. A total of 109 consecutive patients who were over 18 years of age with confirmed SARS-CoV-2 and endemic HCoVs were enrolled. Finally, 19 patients with SARS-CoV-2 CAP were compared to 40 patients with endemic HCoV CAP. Flu-like symptoms such as cough, sore throat, headache, myalgia, and prolonged fever were more common in SARS-CoV-2 CAP, whereas clinical findings suggestive of bacterial pneumonia such as dyspnea, leukocytosis with left shift, and increased C-reactive protein were more common in endemic HCoV CAP. Bilateral peripherally distributed ground-glass opacities (GGOs) were typical radiologic findings in SARS-CoV-2 CAP, whereas mixed patterns of GGOs, consolidations, micronodules, and pleural effusion were observed in endemic HCoV CAP. Coinfection was not observed in patients with SARS-CoV-2 CAP, but was observed in more than half of the patients with endemic HCoV CAP. There were distinctive differences in the clinical and radiologic findings between SARS-CoV-2 and endemic HCoV CAP. Further investigations are required to elucidate the mechanism underlying this difference. Follow-up observations are needed to determine if the presentation of SARS-CoV-2 CAP changes with repeated infection.

Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: a population-based cohort study.

OBJECTIVES: Early in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ. METHODS: We conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, χ2, and Student's t-tests. RESULTS: As of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200-400 mg/day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86). CONCLUSIONS: HCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.