Effect of Wearing Personal Protective Equipment (PPE) for COVID-19Treatment on Blood Culture Contamination: Implication for Optimal PPE Strategies

The personal protective equipment (PPE) used to minimize exposure to hazards can hinder healthcare workers from performing sophisticated procedures. We retrospectively reviewed 77,535 blood cultures (202,012 pairs) performed in 28,502 patients from January 2020 to April 2022. The contamination rate of all blood cultures was significantly elevated in the coronavirus disease 2019 ward at 4.68%, compared to intensive care units at 2.56%, emergency rooms at 1.13%, hematology wards at 1.08%, and general wards at 1.07% (All of P < 0.001). This finding implies that wearing PPE might interfere with adherence to the aseptic technique. Therefore, a new PPE policy is needed that considers the balance between protecting healthcare workers and medical practices.

Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes of Staphylococcus aureus Bacteremia

Background@#Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. @*Methods@#Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. @*Results@#Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). @*Conclusion@#The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.

Evaluation of Seropositivity after Standard Doses of Vaccination against SARS-CoV-2 in Early Breast Cancer Patients Receiving Adjuvant Treatment

BackgroundCoronavirus disease 2019 (COVID-19) pandemic affected millions of individuals and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data is available on their efficacy in patients under active anti-cancer therapies. Materials and MethodsIn this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination in early breast cancer patients with concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. ResultsStandard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. ConclusionOur study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations. Implications for PracticeIn this article, we present rare data on the homogeneous population of patients with early breast cancer under active anti-cancer treatments. The patients showed adequate serologic responses against SARS-CoV-2 virus after standard doses of vaccination without serious adverse events in concurrence with active adjuvant anti-cancer therapy. The patients receiving concurrent cytotoxic chemotherapy, however, have significantly lower serum anti-spike antibody titers than those under non-cytotoxic anti-cancer treatments or without treatments. Selection of the COVID-19 vaccines should be based on personalized risk stratification considering the use of concurrent cytotoxic chemotherapy and the patients medical circumstances. Booster doses of vaccination could be considered for the vulnerable population, such as elderly with comorbidities and the single standard dose of vaccination.

Clinical Impact of Empirical Antibiotic Therapy in Patients With Coronavirus Disease 2019 Requiring Oxygen Therapy

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically.However, the prognostic impact of empirical antibiotic therapy has not been evaluated.We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.

Breakthrough COVID-19 Infection During the Delta Variant Dominant Period: Individualized Care Based on Vaccination Status Is Needed

Background@#The clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon. @*Methods@#We retrospectively analyzed hospitalized COVID-19 patients during a delta variantdominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status. @*Results@#A total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients. @*Conclusion@#In the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.

Kinetics of Neutralizing Antibody Responses Against SARS-CoV-2 Delta Variant in Patients Infected at the Beginning of the Pandemic

We investigated the kinetics of the neutralizing antibody responses to the severe acute respiratory syndrome-coronavirus-2 delta variant over the course of 1 year in 16 patients infected at the beginning of the pandemic. In patients with severe disease, neutralizing responses to the delta variant were detectable, albeit at lower levels than responses to the wild type. Neutralizing responses to the delta variant were undetectable, however, in asymptomatic persons. This finding implies that the vaccination strategy for persons with past natural infection should depend on the severity of the previous infection.

Changes in Anxiety Level and Personal Protective Equipment Use Among Healthcare Workers Exposed to COVID-19

Background@#The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). @*Methods@#An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. @*Results@#The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available.Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. @*Conclusion@#Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.

How We Have Treated Severe to Critically Ill Patients With Coronavirus Disease 2019 in Korea

Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, and the coronavirus disease 2019 (COVID-19) pandemic currently continues.In response to this unprecedented pandemic, several researchers and medical staff have struggled to find appropriate treatments for COVID-19. Patients with mild symptoms can recuperate with symptomatic care, however establishing treatment for severe to critically ill patients who can have a high mortality has been essential. Accordingly, the guidelines for COVID-19 treatment have evolved through numerous trials and errors and have been relatively well established to date. In the Republic of Korea, several evidence-based guidelines for COVID-19 treatment were released and revised, reflecting various research and regional medical conditions. To date, approximately 3 years after the beginning of the COVID-19 pandemic, we are reflecting on the changes in the guidelines thus far and have summarized the treatment experience of severe to critically ill patients with COVID-19. The Korean guidelines for COVID-19 treatment have been updated continuously as the National Institutes of Health (NIH) guidelines have changed. Dexamethasone is currently used as the backbone for the treatment of severe to critically ill patients with COVID-19, and remdesivir, baricitinib, and tocilizumab can be added depending on a patient’s situation. In addition, venous thromboembolism prophylaxis is one of the important adjunctive therapies for patients with severe COVID-19. In the clinical field, treatment of severely ill patients with COVID-19 based on guidelines is widely practiced by medical staff and established currently.

Clinical and immunological signatures of severe COVID-19 in previously healthy patients with clonal hematopoiesis

Identifying additional risk factors for COVID-19 severity in numerous previously healthy patients without canonical clinical risk factors remains challenging. In this study, we investigate whether clonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes various inflammatory responses, may exert COVID-19 severity. We examine the clinical impact of CHIP in 143 laboratory-confirmed COVID-19 patients. Both stratified analyses and logistic regression including the interaction between canonical risk factors and CHIP show that CHIP is an independent risk factor for severe COVID-19, especially in previously healthy patients. Analyses of 60,310 single-cell immune transcriptome profiles identify distinct immunological signatures for CHIP (+) severe COVID-19 patients, particularly in classical monocytes, with a marked increase in pro-inflammatory cytokine responses and potent IFN-{gamma} mediated hyperinflammation signature. We further demonstrate that the enhanced expression of CHIP (+) specific IFN-{gamma} response genes is attributed to the CHIP mutation-dependent epigenetic reprogramming of poised or bivalent cis-regulatory elements. Our results highlight a unique immunopathogenic mechanism of CHIP in the progression of severe COVID-19, which could be extended to elucidate how CHIP contributes to a variety of human infectious diseases.

Surface-aerosol stability and pathogenicity of diverse MERS-CoV strains from 2012 - 2018

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a coronavirus that infects both humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. While some mutations found in camel-derived MERS-CoV strains have been characterized, the majority of natural variation found across MERS-CoV isolates remains unstudied. Here we report on the environmental stability, replication kinetics and pathogenicity of several diverse isolates of MERS-CoV as well as SARS-CoV-2 to serve as a basis of comparison with other stability studies. While most of the MERS-CoV isolates exhibited similar stability and pathogenicity in our experiments, the camel derived isolate, C/KSA/13, exhibited reduced surface stability while another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that while betacoronaviruses may have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the importance of continual, global viral surveillance.

Is it feasible and effective to provide faculty development programs online for clinical teachers? / 한국의학교육

Purpose@#Seoul National University College of Medicine operates a faculty development program for clinical teachers at multiple affiliated teaching hospitals. In 2020, the program was moved online due to coronavirus disease 2019. The purpose of this study was to determine whether it is feasible and effective to provide faculty development programs online in terms of clinical teachers’ participation and satisfaction in comparison with offline programs. @*Methods@#Clinical teachers participated in the clinical teaching methods programs offline in 2019 and online in 2020. We analyzed participation rate and satisfaction level. All surveys items were rated on a 5-point Likert scale. We also interviewed instructors about the advantages and drawbacks of the online program. @*Results@#The participation rate of the online program (89.5%) was significantly higher than that of the offline program (67.8%). The overall satisfaction level for the online program (4.37) was similar to that for the offline program (4.50). @*Conclusion@#Faculty development programs online are feasible and effective in medical education. We need to design training content that fits online programs, consider various online training methods to reinforce the strengths of online programs, and support participants to make good use of these programs.

Work Restrictions for Healthcare Personnel with Potential In-hospital Exposure to SARS-CoV-2: Experience at a Tertiary Hospital

Applying work restrictions for asymptomatic healthcare personnel (HCP) with potential exposure to coronavirus disease 2019 (COVID-19) is recommended to prevent transmission from potentially contagious HCP to patients and other HCP. However, it can lead to understaffing, which threatens the safety of both patients and HCP. We evaluated 203 COVID-19 exposure events at a single tertiary hospital from January 2020 to June 2021. A total of 2,365 HCP were potentially exposed, and work restrictions were imposed on 320 HCP, leading to the loss of 3,311 working days. However, only one of the work-restricted HCP was confirmed with COVID-19. During the study period, the work restriction measures might be taken excessively compared to their benefit, so establishing more effective standards for work restriction is required.

Antibody Responses One Year after Mild SARS-CoV-2 Infection

Understanding the long-term kinetics of antibodies in coronavirus disease 2019 (COVID-19) is essential in interpreting serosurvey data. We investigated the antibody response one year after infection in 52 mildly symptomatic patients with severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection, using three commercial immunoassays and a surrogate virus neutralization test (sVNT) kit. Anti-N pan-immunoglobulin (Ig), anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the antibody could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients.

Clinical Application of the Standard Q COVID-19 Ag Test for the Detection of SARS-CoV-2 Infection

We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test.We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8–32.0%) and 100% (95% CI, 95.3–100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7–46.1%), and 41.1% (95% CI, 21.6–64.0%), respectively.

Is it feasible and effective to provide faculty development programs online for clinical teachers? / 한국의학교육

Purpose@#Seoul National University College of Medicine operates a faculty development program for clinical teachers at multiple affiliated teaching hospitals. In 2020, the program was moved online due to coronavirus disease 2019. The purpose of this study was to determine whether it is feasible and effective to provide faculty development programs online in terms of clinical teachers’ participation and satisfaction in comparison with offline programs. @*Methods@#Clinical teachers participated in the clinical teaching methods programs offline in 2019 and online in 2020. We analyzed participation rate and satisfaction level. All surveys items were rated on a 5-point Likert scale. We also interviewed instructors about the advantages and drawbacks of the online program. @*Results@#The participation rate of the online program (89.5%) was significantly higher than that of the offline program (67.8%). The overall satisfaction level for the online program (4.37) was similar to that for the offline program (4.50). @*Conclusion@#Faculty development programs online are feasible and effective in medical education. We need to design training content that fits online programs, consider various online training methods to reinforce the strengths of online programs, and support participants to make good use of these programs.

Work Restrictions for Healthcare Personnel with Potential In-hospital Exposure to SARS-CoV-2: Experience at a Tertiary Hospital

Applying work restrictions for asymptomatic healthcare personnel (HCP) with potential exposure to coronavirus disease 2019 (COVID-19) is recommended to prevent transmission from potentially contagious HCP to patients and other HCP. However, it can lead to understaffing, which threatens the safety of both patients and HCP. We evaluated 203 COVID-19 exposure events at a single tertiary hospital from January 2020 to June 2021. A total of 2,365 HCP were potentially exposed, and work restrictions were imposed on 320 HCP, leading to the loss of 3,311 working days. However, only one of the work-restricted HCP was confirmed with COVID-19. During the study period, the work restriction measures might be taken excessively compared to their benefit, so establishing more effective standards for work restriction is required.

Antibody Responses One Year after Mild SARS-CoV-2 Infection

Understanding the long-term kinetics of antibodies in coronavirus disease 2019 (COVID-19) is essential in interpreting serosurvey data. We investigated the antibody response one year after infection in 52 mildly symptomatic patients with severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection, using three commercial immunoassays and a surrogate virus neutralization test (sVNT) kit. Anti-N pan-immunoglobulin (Ig), anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the antibody could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients.

Clinical Application of the Standard Q COVID-19 Ag Test for the Detection of SARS-CoV-2 Infection

We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test.We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8–32.0%) and 100% (95% CI, 95.3–100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7–46.1%), and 41.1% (95% CI, 21.6–64.0%), respectively.

Can reactogenicity predict immunogenicity after COVID-19 vaccination?

Background/Aims@#This study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. @*Methods@#Adverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics. @*Results@#The median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group. @*Conclusions@#Local and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.

Prevalence of Multidrug-Resistant Tuberculosis in HIV/Tuberculosis Co-Infected Patients / 감염과화학요법

Tuberculosis (TB) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Patients with multidrug-resistant (MDR)-TB have poor outcomes.This study aimed to determine the prevalence of MDR-TB in HIV/TB co-infected patients in the Korea. We reviewed the medical records of HIV/TB co-infected patients at two university hospitals between January 1998 and December 2020. During the study period, a total of 87 HIV/TB co-infected patients were identified, and drug susceptibility test results were available for 44 of them. The prevalence of MDR-TB in the study population was 15.9% (7/44, 95% confidence interval, 5.1 - 26.7).