Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Longitudinal Analysis of Memory T-Cell Responses in Survivors of Middle East Respiratory Syndrome.

BACKGROUND: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a zoonotic betacoronavirus. The development of effective vaccines and control measures requires a thorough understanding of the immune response to this viral infection. METHODS: We investigated cellular immune responses up to 5 years after infection in a cohort of 59 MERS survivors by performing enzyme-linked immunospot assay and intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with synthetic viral peptides. RESULTS: Memory T-cell responses were detected in 82%, 75%, 69%, 64%, and 64% of MERS survivors from 1-5 years post-infection, respectively. Although the frequency of virus-specific interferon gamma (IFN-γ)-secreting T cells tended to be higher in moderately/severely ill patients than in mildly ill patients during the early period of follow-up, there was no significant difference among the different clinical severity groups across all time points. While both CD4+ and CD8+ T cells were involved in memory T-cell responses, CD4+ T cells persisted slightly longer than CD8+ T cells. Both memory CD4+ and CD8+ T cells recognized the E/M/N proteins better than the S protein and maintained their polyfunctionality throughout the period examined. Memory T-cell responses correlated positively with antibody responses during the initial 3-4 years but not with maximum viral loads at any time point. CONCLUSIONS: These findings advance our understanding of the dynamics of virus-specific memory T-cell immunity after MERS-coronavirus infection, which is relevant to the development of effective T cell-based vaccines.

Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis.

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 ± 0.016, 0.053 ± 0.017, 0.043 ± 0.016, and 0.019 ± 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 ± 0.028 for the HRZE group and 0.154 ± 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483.

Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: A National Population-Based Cohort Study.

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.

Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis.

BACKGROUND: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid. METHODS: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions. RESULTS: Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 µg per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 µg per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 µg per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater. CONCLUSIONS: This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).

Comparison of Long Term Follow-up Chest CT Imaging in Adult and Pediatric Patients with Humidifier Disinfectant-related Lung Injury.

BACKGROUND: To compare the chest computed tomography (CT) images of children and adults in families with clusters of humidifier disinfectant-related lung injury (HDLI) after cessation of exposure to humidifier disinfectant (HD). METHODS: We reviewed medical records of 19 families with 43 patients (21 adults, 22 children) among families, which had at least one adult and one child with HDLI. Each family was exposed to the same HD exposure environment. RESULTS: In adults, centrilobular nodules were predominant (95.2%) in chronic HDLI findings after cessation of exposure to HD, however, in children, normal pattern was most prevalent on chest CT (45.5%), followed by centrilobular nodule (36.4%), bizarre lung cysts (36.4%), and reticulation (13.6%). CONCLUSION: Unlike the known chronic HDLI finding of adults, centrilobular nodules were only present in 36.4% of children. The frequency of bizarre lung cysts were significantly greater in children than that in adults after cessation of similar exposure to HD. Thus, bizarre lung cysts may be useful as another novel finding of chronic HDLI in children who have no history of pulmonary infection or other perinatal disorder such as hyaline membrane disease or other interstitial lung disease.

Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection.

BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus-reactive CD8+ T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4+ T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8+ T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8+ T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.

Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome.

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.

The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015.

BACKGROUND: In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient. CASE PRESENTATION: A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015. CONCLUSIONS: The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus.

Microevolution of Outbreak-Associated Middle East Respiratory Syndrome Coronavirus, South Korea, 2015.

During the 2015 Middle East respiratory syndrome coronavirus outbreak in South Korea, we sequenced full viral genomes of strains isolated from 4 patients early and late during infection. Patients represented at least 4 generations of transmission. We found no evidence of changes in the evolutionary rate and no reason to suspect adaptive changes in viral proteins.

A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results.

A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.

Differential expression of CD57 in antigen-reactive CD4+ T cells between active and latent tuberculosis infection.

The development of diagnostic tests that predict the progression of latent tuberculosis infection to active disease is pivotal for the eradication of tuberculosis. As an initial step to achieve this goal, our study's aim was to identify biomarkers that differentiate active from latent tuberculosis infection. We compared active and latent tuberculosis infection groups in terms of the precursor frequency, functional subset differentiation, and senescence/exhaustion surface marker expression of antigen-specific CD4(+) T cells, which were defined as dividing cells upon their encountering with Mycobacterium (M.) tuberculosis antigens. Among several parameters shown to have statistically significant differences between the two groups, the frequency of CD57-expressing cells could differentiate effectively between active disease and latent infection. Our results suggest that the expression of CD57 in M. tuberculosis-reactive CD4(+) T cells could be a promising candidate biomarker with which to identify individuals with latent tuberculosis infection prone to progression to active disease.

Linezolid for treatment of chronic extensively drug-resistant tuberculosis.

BACKGROUND: Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS: We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS: By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS: Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).

Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital.

Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012.

BACKGROUND: Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea. METHODS: New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed. RESULTS: The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ≥3 previous TB episodes, ≥1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ≥35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ≥50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history. CONCLUSIONS: Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00341601.

ECMO is associated with decreased hospital mortality in COVID-19 ARDS.

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020-December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36-0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11-0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups.

Exploring alternative biomaterials for diagnosis of pulmonary tuberculosis in HIV-negative patients by use of the GeneXpert MTB/RIF assay.

The utility of the GeneXpert MTB/RIF (Xpert) assay for detection of Mycobacterium tuberculosis in sputum samples has been extensively studied. However, the performance of the Xpert assay as applied to other readily accessible body fluids such as exhaled breath condensate (EBC), saliva, urine, and blood has not been established. We used the Xpert assay to test EBC, saliva, urine, and blood samples from HIV-negative, smear- and culture-positive pulmonary tuberculosis (TB) patients for the presence of M. tuberculosis. To compare the ability of the assay to perform bacterial load measurements on sputum samples with versus without sample processing, the assay was also performed on paired direct and processed sputum samples from each patient. The Xpert assay detected M. tuberculosis in none of the 26 EBC samples (sensitivity, 0.0%; 95% confidence interval [95% CI], 0.0%, 12.9%), 10 of the 26 saliva samples (sensitivity, 38.5%; 95% CI, 22.4%, 57.5%), 1 of 26 urine samples (sensitivity, 3.8%; 95% CI, 0.7%, 18.9%), and 2 of 24 blood samples (sensitivity, 8.3%; 95% CI, 2.3%, 25.8%). For bacterial load measurements in the different types of sputum samples, the cycle thresholds of the two M. tuberculosis-positive sputum types were well correlated (Spearman correlation of 0.834). This study demonstrates that the Xpert assay should not be routinely used to detect M. tuberculosis in EBC, saliva, urine, or blood samples from HIV-negative patients suspected of having pulmonary tuberculosis. As a test of bacterial load, the assay produced similar results when used to test direct versus processed sputum samples. Sputum remains the optimal sample type for diagnosing pulmonary tuberculosis in HIV-negative patients with the Xpert assay.

Comparison of maternal and neonatal survival exposed to humidifier disinfectants during perinatal periods: a case-series study.

A humidifier disinfectant (HD) has been prohibited by the government due to its serious effects on the human body. Several studies on the relationship between HD and lung diseases have been performed independently on children and adults. However, there have been no reports on the effects of HD exposure on pregnant women and their foetuses. Therefore, the present study was conducted to investigate the effects of HD exposure on the foetuses of women who encountered HD during pregnancy. A total of 56 cases were recruited from 2017 to 2019 through the Korea Environmental Industry & Technology Institute, and data obtained from the medical records included maternal date of birth, maternal date of death, maternal start and end date of HD exposure, maternal date of symptom onset, neonatal birthday, neonatal birthweight, gestational age, and neonatal survival status within 28 days. All data were retrospectively investigated through medical records. Of the 47 mothers, 20 (42.6%) mothers survived, and 27 (57.4%) mothers died. In the group of survivors, there was a shorter period of total HD use, period of HD use before pregnancy and period of HD use to onset of symptoms. Shorter durations of HD use resulted in higher survival rate of mothers. HD use caused an increase in gestational age surviving foetuses, and foetal mortality increased when clinical symptoms developed before birth.

Predictive Factors and Clinical Impacts of Delayed Isolation of Tuberculosis during Hospital Admission.

Delayed isolation of tuberculosis (TB) can cause unexpected exposure of healthcare workers (HCWs). This study identified the predictive factors and clinical impact of delayed isolation. We retrospectively reviewed the electronic medical records of index patients and HCWs who underwent contact investigation after TB exposure during hospitalization at the National Medical Center, between January 2018 and July 2021. Among the 25 index patients, 23 (92.0%) were diagnosed with TB based on the molecular assay, and 18 (72.0%) had a negative acid-fast bacilli smear. Sixteen (64.0%) patients were hospitalized via the emergency room, and 18 (72.0%) were admitted to a non-pulmonology/infectious disease department. According to the patterns of delayed isolation, patients were classified into five categories. Among 157 close-contact events in 125 HCWs, 75 (47.8%) occurred in Category A. Twenty-five (20%) HCWs had multiple TB exposures (n = 57 events), of whom 37 (64.9%) belonged to Category A (missed during emergency situations). After contact tracing, latent TB infection was diagnosed in one (1.2%) HCW in Category A, who was exposed during intubation. Delayed isolation and TB exposure mostly occurred during pre-admission in emergency situations. Effective TB screening and infection control are necessary to protect HCWs, especially those who routinely contact new patients in high-risk departments.