Correlates of burnout among healthcare workers during the COVID-19 pandemic in South Korea.

Burnout is a form of negative emotional and physical response to job stress. This study aimed to investigate the prevalence of burnout among healthcare workers responding to the coronavirus disease 2019 (COVID-19) outbreak in Korea and to explore correlates of burnout among healthcare workers. A nationwide questionnaire-based survey was conducted from December 1, 2020, to January 29, 2021 on 1425 healthcare workers who worked in one of the 16 healthcare facilities designated for COVID-19 care, in public health centers, or as paramedics in Korea. Burnout was assessed using 16 Korean-adapted items based on the Oldenburg Burnout Inventory (OLBI). Data were collected using a structured questionnaire and analyzed using the R version 4.1.1 software program. OLBI results indicate clinically exhaustion in 84.5% (1204/1425) and clinically disengagement in 91.1% (1298/1425), and 77.3% (1102/1425) met the score criteria for both the exhaustion and disengagement subscales for burnout. Burnout rate was significantly increased in the group with chronic fatigue symptoms (Fatigue Severity Scale ≥ 3.22) after the outbreak of COVID-19 (OR, 3.94; 95% CI 2.80-5.56), in the female group (OR, 2.05; 95% CI 1.46-2.86), in the group with physical symptoms (Patient Health Questionnaire-15 ≥ 10) after the outbreak of COVID-19 (OR, 2.03; 95% CI 1.14-3.60), in the group with a higher Global Assessment of Recent Stress scale (OR, 1.71; 95% CI 1.46-2.01), in the group with post-traumatic stress symptoms (Primary Care Post-Traumatic Stress Disorder-5 ≥ 2) (OR, 1.47; 95% CI 1.08-2.01), and in the younger age group(OR, 1.45; 95% CI 1.22-1.72). The chronic fatigue symptoms were correlated with cumulative days of care (OR, 1.18; 95% CI 1.02-1.37). The physical symptoms were correlated with average contact hours with COVID-19 patients per day (OR, 1.34; 95% CI 1.17-1.54), and cumulative days of care (OR, 1.21; 95% CI 1.06-1.38). Most Korean healthcare workers suffered from burnout related to excessive workload during the COVID-19 pandemic. During a widespread health crisis like COVID-19, it is necessary to regularly check the burnout status in healthcare workers and reduce their excessive workload by supplementing the workforce and providing appropriate working hours sufficient rest hours.

COVID-19 Outbreak in Daegu City, Korea and Response to COVID-19: How Have We Dealt and What Are the Lessons?

The first coronavirus disease 2019 (COVID-19) outbreak in Daegu city was overcome by efforts, including; 1) prompt isolation and quarantine action by local government with cooperative help from expert groups and the central government, 2) high-intensity social distancing and active cooperation of citizens, 3) admission of asymptomatic and mild patients in 'residential treatment centers', and 4) use of a telephone scoring system for the allocation of patients, with a mortality rate of 2.5%. A continuous suppression policy with test, tracing, and treatment (3 Ts) was implemented as an active response to the initial outbreaks in Korea. With the introduction of vaccines and therapeutic agents, the COVID-19 crisis had improved. Recently, the omicron variant was responsible for most domestic outbreaks, albeit with a low mortality rate (0.1%). Since the omicron outbreak, a damage mitigation policy has been implemented, focusing on protecting vulnerable groups. In the future, preparation including below are needed; 1) improving the national public health emergency response system, 2) strengthening the crisis response capacity of local governments, 3) cooperation between public healthcare and private healthcare, and 4) establishing a resilient medical response system.

Machine learning models to predict the maximum severity of COVID-19 based on initial hospitalization record.

Background: As the worldwide spread of coronavirus disease 2019 (COVID-19) continues for a long time, early prediction of the maximum severity is required for effective treatment of each patient. Objective: This study aimed to develop predictive models for the maximum severity of hospitalized COVID-19 patients using artificial intelligence (AI)/machine learning (ML) algorithms. Methods: The medical records of 2,263 COVID-19 patients admitted to 10 hospitals in Daegu, Korea, from February 18, 2020, to May 19, 2020, were comprehensively reviewed. The maximum severity during hospitalization was divided into four groups according to the severity level: mild, moderate, severe, and critical. The patient's initial hospitalization records were used as predictors. The total dataset was randomly split into a training set and a testing set in a 2:1 ratio, taking into account the four maximum severity groups. Predictive models were developed using the training set and were evaluated using the testing set. Two approaches were performed: using four groups based on original severity levels groups (i.e., 4-group classification) and using two groups after regrouping the four severity level into two (i.e., binary classification). Three variable selection methods including randomForestSRC were performed. As AI/ML algorithms for 4-group classification, GUIDE and proportional odds model were used. For binary classification, we used five AI/ML algorithms, including deep neural network and GUIDE. Results: Of the four maximum severity groups, the moderate group had the highest percentage (1,115 patients; 49.5%). As factors contributing to exacerbation of maximum severity, there were 25 statistically significant predictors through simple analysis of linear trends. As a result of model development, the following three models based on binary classification showed high predictive performance: (1) Mild vs. Above Moderate, (2) Below Moderate vs. Above Severe, and (3) Below Severe vs. Critical. The performance of these three binary models was evaluated using AUC values 0.883, 0.879, and, 0.887, respectively. Based on results for each of the three predictive models, we developed web-based nomograms for clinical use (http://statgen.snu.ac.kr/software/nomogramDaeguCovid/). Conclusions: We successfully developed web-based nomograms predicting the maximum severity. These nomograms are expected to help plan an effective treatment for each patient in the clinical field.

Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea.

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Estimation of SARS-CoV-2 Neutralizing Activity and Protective Immunity in Different Vaccine Types Using Three Surrogate Virus Neutralization Test Assays and Two Semiquantitative Binding Assays Targeting the Receptor-Binding Domain.

Estimating neutralizing activity in vaccinees is crucial for predicting the protective effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the plaque reduction neutralization test (PRNT) requires a biosafety level 3 facility, it would be advantageous if surrogate virus neutralization test (sVNT) assays and binding assays could predict neutralizing activity. Here, five different assays were evaluated with respect to the PRNT in vaccinees: three sVNT assays from GenScript, Boditech Med, and SD Biosensor and two semiquantitative binding assays from Roche and Abbott. The vaccinees were subjected to three vaccination protocols: homologous ChAdOx1, homologous BNT162b2, and heterologous administration. The ability to predict a 50% neutralizing dose (ND50) of ≥20 largely varied among the assays, with the binding assays showing substantial agreement (kappa, ~0.90) and the sVNT assays showing relatively poor performance, especially in the ChAdOx1 group (kappa, 0.33 to 0.97). The ability to predict an ND50 value of ≥118.25, indicating a protective effect, was comparable among different assays. Applying optimal cutoffs based on Youden's index, the kappa agreements were greater than 0.60 for all assays in the total group. Overall, relatively poor performance was demonstrated in the ChAdOx1 group, owing to low antibody titers. Although there were intra-assay differences related to the vaccination protocols, as well as interassay differences, all assays demonstrated fair performance in predicting the protective effect using the new cutoffs. This study demonstrates the need for a different cutoff for each assay to appropriately determine a higher neutralizing titer and suggests the clinical feasibility of using various assays for estimation of the protective effect. IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic continues to last, despite high COVID-19 vaccination rates. As many people experience breakthrough infection after prior infection and/or vaccination, estimating the neutralization activity and predicting the protective effect are major issues of concern. However, since standard neutralization tests are not available in most clinical laboratories, it would be beneficial if commercial assays could predict these aspects. In this study, we evaluated the performance of three sVNT assays and two semiquantitative binding assays targeting the receptor-binding domain with respect to the PRNT. Our results suggest that these assays could be used for predicting the protective effect by adjusting the cutoffs.

Kinetics of vaccine-induced neutralizing antibody titers and estimated protective immunity against wild-type SARS-CoV-2 and the Delta variant: A prospective nationwide cohort study comparing three COVID-19 vaccination protocols in South Korea.

Introduction: Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy. Methods: We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant. Results: We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2-99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7-100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0-87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT). Conclusion: Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.

Kinetics of neutralizing antibodies against SARS-CoV-2 infection according to sex, age, and disease severity.

Knowledge of the factors affecting the difference in kinetics and longevity of the neutralizing antibody (nAb) response to SARS-CoV-2 is necessary to properly prioritize vaccination. In the present study, from March to December 2020, of the 143 patients who recovered from COVID-19, 87 underwent study visits scheduled every 3 months. Patient demographics and blood samples were collected followed by a plaque reduction neutralization test to analyze nAb titers. A linear mixed model was used to compare the effects of sex, age, and disease severity over time. Results demonstrated a gradual reduction in nAb titers over time with a significant decrease from 6 to 9 months post-COVID-19 infection (p < 0.001). In time-to-sex, age, and disease severity comparisons, reduction in nAb titers over time was unaffected by sex (p = 0.167), age (p = 0.188), or disease severity (p = 0.081). Additionally, the nAb titer was 1.46 times significantly higher in those aged ≥ 50 years than in those aged < 50 years (p = 0.036) irrespective of time Moreover, the nAb titer was 2.41 times higher in the moderate or above than that in the below moderate disease severity group (p < 0.001). However, no significant differences were observed in terms of sex (p = 0.300). Given the reduction in nAbs over time, maintaining protective neutralizing antibodies regardless of sex, age, or disease severity is needed.

Clinical Application of a Solid-Phase Assay for SARS-CoV-2 IgG to Predict a Neutralizing Antibody Titer.

BACKGROUND: To assess protective immunity among a general population against severe acute respiratory syndrome coronavirus 2, the correlation of the commercially available solid-phase assay (SPA) for SARS-CoV-2 IgG with a neutralization assay must be investigated. METHODS: Both the neutralization assay and SPA were performed on samples of 143 recovered coronavirus disease 2019 (COVID-19) patients. SARS-CoV-2 IgG was measured using two SPAs for the chemiluminescence immunoassay principle with different target proteins: nucleocapsid and spike protein (Architect i2000SR [Abbott] and Liaison XL [DiaSorin], respectively). The plaque reduction neutralization test (PRNT) was conducted to obtain titers for the neutralizing antibody. RESULTS: All patients had PRNT titers ranging from 10 to 2,560. Spike Ab SPA had greater sensitivity than nucleocapsid Ab SPA (81.1% [116/143] and 70.6% [101/143], respectively, p = 0.003). The values measured for both SPAs had a positive correlation with the PRNT titers (both R = 0.77, p < 0.001). To predict a high PRNT titer (≥ 160), cutoff values of two SPAs were adjusted based on receiver-operating characteristics curve analysis. The nucleocapsid Ab SPA (cutoff index of 4.17) attained 90.3% sensitivity and 75.9% specificity, whereas the spike Ab SPA (cutoff value of 109 unit/mL) attained 87.1% sensitivity and 89.3% specificity. Therefore, the spike Ab SPA had greater specificity than the nucleocapsid Ab SPA (p = 0.003). CONCLUSIONS: The qualitative SPA for nucleocapsid Ab, as well as the quantitative SPA for spike Ab, had a modest positive correlation with the neutralization assay. However, spike Ab SPA was more suitable for neutralizing capacity.

Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial.

Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19-85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19-55 years; stage II, 240 healthy adults aged 19-85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Healthcare Workforce Response to The Coronavirus Disease Outbreak in Daegu, Korea: A Multi-Center, Cross-Sectional Survey.

BACKGROUND: Securing an available healthcare workforce is critical to respond to coronavirus disease 2019 (COVID-19); however, research investigating Korea's COVID-19 staffing response is rare. To present the fundamental data of healthcare staff in response to the surge in COVID-19 cases, we investigated the healthcare workforce response in Daegu, South Korea, which experienced the first largest outbreak of COVID-19 outside of China. MATERIALS AND METHODS: In response to the COVID-19 outbreak, this retrospective cross-sectional study analyzed data on the scale and characteristics of healthcare workers (HCWs). Additionally, it analyzed the clinical and epidemiological characteristics of HCWs infected with COVID-19 in six major teaching hospitals (five tertiary and one secondary) in Daegu from January 19 to April 30, 2020. RESULTS: During this study period, only 1.3% (n = 611) of the total hospitalized patients (n = 48,807) were COVID-19 inpatients, but they occupied 6.0% (n = 303) of the total hospital beds (n = 5,056), and 23.7% (n = 3,471) of all HCWs (n = 14,651) worked in response to COVID-19. HCWs participating in COVID-19-related works comprised 50.6% (n = 1,203) of doctors (n = 2,379), 26.3% (n = 1,571) of nurses (n = 5,982), and 11.4% (n = 697) of other HCWs (n = 6,108). Only 0.3% (n = 51) of HCWs (n = 14,651) developed COVID-19 infections from community-acquired (66.7%) or hospital-acquired (29.4%). Nurses were affected predominantly (33.3%), followed by doctors (9.8%), caregivers (7.8%), radiographers (5.9%), and others (45.1%), including nurse aides and administrative, facility maintenance, telephone appointment centers, and convenience store staff. All HCWs infected with COVID-19 recovered completely. The 32.7% (n = 333) of individuals (n = 1,018) exposed to HCWs who had COVID-19 were quarantined, and only one case of secondary transmission among them occurred. CONCLUSION: The COVID-19 pandemic has necessitated significant staffing and facility usage, which is disproportionate to the relatively low number of COVID-19 inpatients, imposing a substantial burden on healthcare resources. Therefore, beyond the current reimbursement level of the Korean National Health Insurance, a new type of rewarding system is needed to prepare hospitals for the emerging outbreaks of infectious diseases. Keeping HCWs safe from COVID-19 is crucial for maintaining the healthcare workforce during a sudden massive outbreak. Further studies are needed to determine the standards of required HCWs through detailed research on the working hours and intensity of HCWs responding to COVID-19.

One Year Follow-Up of COVID-19 Related Symptoms and Patient Quality of Life: A Prospective Cohort Study.

PURPOSE: Globally, concerns have grown regarding the long-term effects of novel coronavirus disease (COVID-19) infection. Therefore, we evaluated the long-term course of persistent symptoms and patient quality of life. MATERIALS AND METHODS: This prospective cohort study was conducted at a single tertiary university hospital from August 31, 2020 to March 29, 2021 with adult patients followed at 6 and 12 months after acute COVID-19 symptom onset or diagnosis. Clinical characteristics, self-reported symptoms, EuroQol 5 dimension 5 level (EQ5D-5L) index scores, Korean version of the Patient Health Questionnaire-9 (PHQ-9), Korean version of the Posttraumatic Stress Disorder Checklist-5 (PCL-5-K), and Generalized Anxiety Disorder-7 (GAD-7) were investigated. Symptom persistent or non-persistent groups were defined according to persistency of COVID-19 related symptoms or signs after acute COVID-19 infection, respectively. RESULTS: Of all 235 patients, 170 (64.6%) patients were eligible for analysis. The median age was 51 (interquartile range, 37-61) years old, and 102 patients were female (60.0%). After 12 months from acute COVID-19 infection, in total, 83 (48.8%) patients still suffered from COVID-19-related symptoms. The most common symptoms included amnesia (24.1%), insomnia (14.7%), fatigue (13.5%), and anxiety (12.9%). Among the five EQ5D-5L categories, the average value of anxiety or depression was the most predominant. PHQ-9 and PCL-5-K scores were statistically higher in the COVID-19-related symptom persistent group than the non-persistent group (p=0.001). However, GAD-7 scores showed no statistical differences between the two groups (p=0.051). CONCLUSION: Neuropsychiatric symptoms were the major COVID-19-related symptoms after 12 months from acute COVID-19 infection, reducing quality of life.

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity.

OBJECTIVES: We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups. METHODS: We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey. RESULTS: We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti-receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52-12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03-1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01-3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND50, 2367.74 [95% CI, 1970.03-2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88-2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16-470.59]; p < 0.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the Delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND50, 872.01 [95% CI, 685.33-1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78-434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 144.05-296.34]). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group. DISCUSSION: Heterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile.

Workload of Healthcare Workers During the COVID-19 Outbreak in Korea: A Nationwide Survey.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea. METHODS: A nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients. RESULTS: Public medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6], P = 0.006). Infectious Diseases physicians are mostly (80%) involved among attending physicians. The number of nurses per patient (median [interquartile range, IQR]) in tertiary-care hospitals was higher than in public medical centers (4.6 [3.4-5] vs. 1.1 [0.8-2.1], P = 0.089). The median number of nurses per patient for COVID-19 patients was higher than the highest national standard in South Korea (3.8 vs. 2 for critical care). All participating healthcare facilities were also operating screening centers, for which a median of 2 doctors, 5 nurses, and 2 administrating staff were necessary. CONCLUSION: As the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.

Regdanvimab in patients with mild-to-moderate SARS-CoV-2 infection: A propensity score-matched retrospective cohort study.

BACKGROUND: Regdanvimab (CT-P59) is a neutralizing antibody authorized in Republic of Korea for the treatment of adult patients with moderate or mild-COVID-19 who are not on supplemental oxygen and have high risk of progressing to severe disease (age ≥ 50 years or comorbidities). This study evaluated the clinical efficacy, safety and medical utilization/costs associated with real-world regdanvimab therapy. METHODS: This non-interventional, retrospective cohort study included adult patients with confirmed mild-to-moderate SARS-CoV-2 infection. Patients treated with regdanvimab were compared with controls who had received other therapies. The primary endpoint was the proportion of patients progressing to severe/critical COVID-19 or death due to SARS-CoV-2 infection up to Day 28. Propensity score matching was applied to efficacy analyses. RESULTS: Overall, 552 patients were included in the Safety and Efficacy Sets (regdanvimab, n = 156; control, n = 396) and 274 patients in the propensity score-matched (PSM) Efficacy Set (regdanvimab, n = 113; control, n = 161). In the PSM Set, the risk of severe/critical COVID-19 or death was significantly lower in the regdanvimab group (7.1% vs 16.1%, P = 0.0263); supplemental oxygen was required by 8.0% and 18.6% of patients in the regdanvimab and control groups, respectively (P = 0.0128). There were no unexpected safety findings in the regdanvimab group. Medical utilization analysis showed an overall cost reduction with regdanvimab compared with control treatments. CONCLUSIONS: Regdanvimab significantly reduced the proportion of patients progressing to severe/critical disease or dying of SARS-CoV-2 infection. This study shows the potential benefits of regdanvimab in reducing disease severity and improving medical utility in patients with COVID-19.

Inflammatory Markers and Cytokines in Moderate and Critical Cases of COVID-19.

BACKGROUND: Inflammatory responses have been suggested to be associated with coronavirus disease 2019 (COVID-19). This study investigated the inflammatory markers and cytokines in COVID-19 according to its severity. METHODS: We enrolled 49 patients with COVID-19, who were classified as either moderate or critical cases. Serum or plasma interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) levels were measured. RESULTS: Lactate dehydrogenase, ferritin, C-reactive protein, and procalcitonin levels were significantly higher in the critical group than in the moderate group (p < 0.001). IL-6 and TNF-α levels were significantly higher in the critical group, with elevated IL-6 levels from the first to third weeks after confirmed PCR (p < 0.05). CONCLUSIONS: Inflammatory markers and cytokines were increased in COVID-19 and closely related to the severity of the disease. We recommend early active monitoring of IL-6 levels along with inflammatory markers for severe COVID-19.

New Scoring System for Predicting Mortality in Patients with COVID-19.

PURPOSE: We aimed to develop a novel mortality scoring system for inpatients with COVID-19 based on simple demographic factors and laboratory findings. MATERIALS AND METHODS: We reviewed and analyzed data from patients who were admitted and diagnosed with COVID-19 at 10 hospitals in Daegu, South Korea, between January and July 2020. We randomized and assigned patients to the development and validation groups at a 70% to 30% ratio. Each point scored for selected risk factors helped build a new mortality scoring system using Cox regression analysis. We evaluated the accuracy of the new scoring system in the development and validation groups using the area under the curve. RESULTS: The development group included 1232 patients, whereas the validation group included 528 patients. In the development group, predictors for the new scoring system as selected by Cox proportional hazards model were age ≥70 years, diabetes, chronic kidney disease, dementia, C-reactive protein levels >4 mg/dL, infiltration on chest X-rays at the initial diagnosis, and the need for oxygen support on admission. The areas under the curve for the development and validation groups were 0.914 [95% confidence interval (CI) 0.891-0.937] and 0.898 (95% CI 0.854-0.941), respectively. According to our scoring system, COVID-19 mortality was 0.4% for the low-risk group (score 0-3) and 53.7% for the very high-risk group (score ≥11). CONCLUSION: We developed a new scoring system for quickly and easily predicting COVID-19 mortality using simple predictors. This scoring system can help physicians provide the proper therapy and strategy for each patient.

Significance and Associated Factors of Long-Term Sequelae in Patients after Acute COVID-19 Infection in Korea.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic has progressed, there has been a growing awareness of the long-term impacts of the COVID-19 infection. However, until recently, there was no published study that investigated COVID-19-related sequelae and related factors for greater than six months from the onset of COVID-19 symptoms or the time of COVID-19 diagnosis in Korea. MATERIALS AND METHODS: Online survey and statistical analysis were conducted by Kyungpook National University Hospital on 5,252 patients diagnosed as COVID-19 between February 18, 2020 and March 14, 2020. Responders aged between 16 and 70 years were included. Long-term sequelae were defined as persistent symptoms or signs ≥ 6 months after acute COVID-19 infection. The survey was conducted from September 8, 2020 to September 10, 2020. Clinical characteristics and self-reported clinical sequelae of the responders were analyzed to investigate the prevalence and factors associated with sequelae using descriptive and multivariate logistic regression analysis. RESULTS: The median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 195 (interquartile range [IQR] 191 - 200) days. The response rate was 17.1% (900 out of 5,252). The median age was 31 (IQR 24.0 - 47.0) years old, and 627 responders were female (69.7%). Regarding the disease severity, 29 (3.2%) were asymptomatic, 763 (84.8%) mild, 86 (9.6%) moderate, 17 (1.9%) severe, and 5 (0.6%) critical. In total, 591 (65.7%) responders suffered from COVID-19-related long-term sequelae and 78 (8.6%) responders were receiving outpatient treatment for COVID-19-related long-term sequelae. The most common symptoms identified during the isolation period were anosmia and ageusia at 44.5% and 43.5%, respectively. Fatigue was the most common long-term sequelae, accounting for 253 (26.2%) responders, followed by concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression, which accounted for over 20%. Female gender was identified as the factor associated with mental and psychological long-term sequelae (P <0.05). CONCLUSION: The results showed that the rate of COVID-19-related long-term sequelae was 65.7%. The most common long-term sequela was fatigue. The risk factor identified was female gender. It was found that the long-term sequelae had various manifestations, including mental and psychological aspects. To improve the care of COVID-19 recovered patients with COVID-19-related long-term sequelae, the participation of a comprehensive and an interdisciplinary group of researchers is required.

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality.

BACKGROUND: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials. METHODS: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints). RESULTS: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; P = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95; P = .03). CONCLUSIONS: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.

Rapid diagnostic testing for antimicrobial stewardship: Utility in Asia Pacific.

Rapid diagnostic testing (RDT) can provide prompt, accurate identification of infectious organisms and be a key component of antimicrobial stewardship (AMS) programs. However, their use is less widespread in Asia Pacific than western countries. Cost can be prohibitive, particularly in less resource-replete settings. A selective approach is required, possibly focusing on the initiation of antimicrobials, for differentiating bacterial versus viral infections and identifying locally relevant tropical diseases. Across Asia Pacific, more data are needed on RDT use within AMS, focusing on the impact on antimicrobial usage, patient morbidity and mortality, and cost effectiveness. Moreover, in the absence of formal guidelines, regional consensus statements to guide clinical practice are warranted. These will provide a regionally relevant definition for RDT; greater consensus on its role in managing infections; advice on implementation and overcoming barriers; and guidance on optimizing human resource capacity. By addressing these issues, the outcomes of AMS programs should improve.

Neutralizing Antibody Responses to SARS-CoV-2 in Korean Patients Who Have Recovered from COVID-19.

PURPOSE: Neutralizing antibodies (NAbs) have been considered effective in preventing and treating viral infections. However, until now, the duration and clinical implications of antibody-mediated nature immunity in Koreans have remained unknown. Therefore, we examined NAbs levels and clinical characteristics in recovered coronavirus disease 2019 (COVID-19) patients. MATERIALS AND METHODS: Blood samples were collected from 143 adult patients who had been diagnosed with and had recovered from COVID-19 from February to March in 2020 at a tertiary-care university-affiliated hospital in Daegu, Korea. A plaque reduction neutralization test was conducted to analyze NAb titers. Individualized questionnaires were used to identify patient clinical information. RESULTS: The median number of days from symptom onset to the blood collection date was 109.0 (104.0; 115.0). The NAb titers ranged from 10 to 2560. The median NAb titer value was 40. Of the 143 patients, 68 (47.6%) patients had NAb titers ≥80, and 31 (21.7%) patients had NAb titers ≥160. The higher the age or disease severity, the higher the NAb titer. In univariate logistic regression, statistically significant predictors of high NAb titers (≥80) were age, myalgia, nausea or vomiting, dyspnea, and disease severity (p<0.05). Multivariable logistic regression showed that age ≥50 years (p=0.013) and moderate or higher disease severity (p<0.001) were factors associated with high NAb titers (≥80). None of the patients had reinfection of COVID-19. CONCLUSION: All recovered patients were found to have NAbs regardless of the NAb titers maintained by natural immunity. Age and disease severity during COVID-19 infection were associated with high NAb titers.