Targeting YAP Activity and Glutamine Metabolism Cooperatively Suppresses Tumor Progression by Preventing Extracellular Matrix Accumulation.

Cancer cells use multiple mechanisms to evade the effects of glutamine metabolism inhibitors. The pathways that govern responses to alterations in glutamine availability within the tumor may represent therapeutic targets for combinatorial strategies with these inhibitors. Here, we showed that targeting glutamine utilization stimulated Yes-associated protein (YAP) signaling in cancer cells by reducing cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent phosphorylation of large tumor suppressor (LATS). Elevated YAP activation induced extracellular matrix (ECM) deposition by increasing secretion of connective tissue growth factor (CTGF) that promoted production of fibronectin and collagen by surrounding fibroblasts. Consequently, inhibiting YAP synergized with inhibition of glutamine utilization to effectively suppress tumor growth in vivo, along with a concurrent decrease in ECM deposition. Blocking ECM remodeling also augmented the tumor suppressive effects of the glutamine utilization inhibitor. Collectively, these data reveal mechanisms by which targeting glutamine utilization increases ECM accumulation and identify potential strategies to reduce ECM levels and increase the efficacy of glutamine metabolism inhibitors.

Inappropriate Peak Inspiratory Flow Rate in the Patients with Stable Chronic Obstructive Pulmonary Disease in Korea.

Background: Inhalation therapy efficacy hinges on proper peak inspiratory flow rate (PIFR) attainment, yet the prevalence of inappropriate PIFR among patients with chronic obstructive pulmonary disease (COPD) remains unstudied in Korea. This study aimed to assess the prevalence of inappropriate PIFR, its correlation with COPD assessment test (CAT) scores, and factors associated with suboptimal PIFR. Methods: We enrolled 108 patients with COPD who had been using the same inhaler for at least one year without exacerbations. PIFR was measured using an inspiratory flow meter (In-Check™ DIAL G16). Demographic, clinical, pulmonary function, and CAT score data were collected. Inappropriate was defined as PIFR < 60L/min for dry power inhaler (DPI) users or > 90L/min for aerosol device users. Results: The cohort comprised 87 (80.6%) men, mean age 71.0 ± 8.5 years, with mean post-bronchodilator forced expiratory volume in one second of 69.1 ± 1.8% predicted. Twenty-nine (26.9%) used aerosol devices, 76 (70.4%) used DPIs, and three (2.8%) used both. Inappropriate PIFRs were found in 17.2% of aerosol device users and 42.1% of DPI users. CAT scores were significantly higher in inappropriate PIFR group than appropriate PIFR group (11.2 ± 7.7 vs 7.5 ± 4.9, P = 0.003). In DPI users, female, shorter height, lower body weight and MVV (maximal voluntary ventilation) were associated with inappropriate PIFR. Conclusions: Prevalence of inappropriate PIFR among patients with COPD is 17.2% for aerosol device users and 42.1% for DPI users. Suboptimal PIFR correlates with female gender, shorter stature, lower weight and MVV in DPI users.

Pneumonia Prevalence Upon Chest Radiography According to Vaccination Status Among Patients Under 50 Years of Age With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is effective in preventing the disease transmission and progression. However, the relatively mild disease course of the omicron variant and the decrease in antibodies over time after vaccination raise questions about the effectiveness of vaccination, especially in young people. We compared the prevalence of pneumonia and chest X-ray severity score according to vaccination status among patients < 50 years old with COVID-19. METHODS: From January 17 to March 17, 2022, 579 patients with COVID-19, who were < 50 years old and had a known vaccination history in our institution, were all included in this study. All patients underwent initial chest radiography, and follow-up chest radiographs were obtained every two days until discharge. Pneumonia was scored from the radiographs using the Brixia scoring system. The scores of the six lung zones were added for a total score ranging from 0 to 18. Patients were divided into four groups according to 10-year age intervals. Differences between groups were analyzed using the χ² or Fisher's exact tests for categorical variables and the Kruskal-Wallis test or analysis of variance for continuous variables. RESULTS: Among patients aged 12-19 years, the prevalence of pneumonia did not differ depending on vaccination status (non-vaccinated vs. vaccinated, 1/47 [2.1%] vs. 1/18 [5.6%]; P = 0.577). Among patients in their 20s, the prevalence of pneumonia was significantly higher among non-vaccinated patients than among vaccinated patients (8/28, 28.6% vs. 7/138, 5.1%, P < 0.001), similar to patients in their 40s (32/52 [61.5%] vs. 18/138 [13.0%]; P < 0.001). The chest X-ray severity score was also significantly higher in non-vaccinated patients than that in vaccinated patients in their 20s to their 40s (P < 0.001), but not among patients aged 12-19 years (P = 0.678). CONCLUSION: In patients aged 20-49 years, vaccinated patients had a significantly lower prevalence of pneumonia and chest X-ray severity score than non-vaccinated patients.

Outcomes of the electromagnetic navigation bronchoscopy using forceps for lung lesion suspected malignancy: A retrospective study.

Many studies have reported electromagnetic navigation bronchoscopy (ENB) diagnostic yields and the importance of size and computed tomography (CT) bronchus sign. This study aimed to determine the diagnostic yield of ENB alone, using forceps biopsy and cytology. We analyzed the factors associated with yield and complications according to gross specimen size. This retrospective study included patients who underwent ENB using forceps for suspected lung lesions on CT between January 2020 and December 2022 in South Korea. Factors related to the ENB diagnostic yield and complications were evaluated, and the impacts of gross specimen size and cytology were analyzed. A total of 276 patients were analyzed. The final diagnostic yield was 75.5% after excluding indeterminate cases. Sensitivity and specificity were 74.2% and 100%, respectively. Pneumothorax developed in 1.4% (4/276) of cases, with no grade 3 or higher bleeding. Univariable analysis showed that the number of biopsies and the size of the gross specimen were related to the diagnosis. Multivariable analyses showed that a larger lesion size on CT was a significant factor for diagnosis. The gross size of the specimens was not significantly associated with epinephrine use. ENB had acceptable diagnostic yield and safety for diagnosing lung lesions with suspected malignancy. Obtaining more tissue through biopsy may not increase bleeding or pneumothorax complications. Identifying patients with lesion characteristics, including CT bronchus sign, would help increase ENB diagnostic yield.

Development of lung cancer risk prediction models based on F-18 FDG PET images.

OBJECTIVE: We aimed to evaluate whether the degree of F-18 fluorodeoxyglucose (FDG) uptake in the lungs is associated with an increased risk of lung cancer and to develop lung cancer risk prediction models using metabolic parameters on F-18 FDG positron emission tomography (PET). METHODS: We retrospectively included 795 healthy individuals who underwent F-18 FDG PET/CT scans for a health check-up. Individuals who developed lung cancer within 5 years of the PET/CT scan were classified into the lung cancer group (n = 136); those who did not were classified into the control group (n = 659). The healthy individuals were then randomly assigned to either the training (n = 585) or validation sets (n = 210). Clinical factors including age, sex, body mass index (BMI), and smoking history were collected. The standardized uptake value ratio (SUVR) and metabolic heterogeneity (MH) index were obtained for the bilateral lungs. Logistic regression models including clinical factors, SUVR, and MH index were generated to quantify the probability of lung cancer development using a training set. The prediction models were validated using a validation set. RESULTS: The lung SUVR and lung MH index in the lung cancer group were significantly higher than in the control group (p < 0.001 and p < 0.001, respectively). In the combined prediction model 1, age, sex, BMI, smoking history, and lung SUVR were significantly associated with lung cancer development (age: OR 1.07, p < 0.001; male: OR 2.08, p = 0.015; BMI: OR 0.93, p = 0.057; current or past smoker: OR 5.60, p < 0.001; lung SUVR: OR 1.13, p < 0.001). In the combined prediction model 2, age, sex, BMI, smoking history, and lung MH index showed a significant association with lung cancer development (age: OR 1.06, p < 0.001; male: OR 1.87, p = 0.045; BMI: OR 0.93, p = 0.010; current or past smoker: OR 4.78, p < 0.001; lung MH index: OR 1.33, p < 0.001). In the validation data, combined prediction models 1 and 2 exhibited very good discrimination [area under the receiver operator curve (AUC): 0.867 and 0.901, respectively]. CONCLUSIONS: The metabolic parameters on F-18 FDG PET are related to an increased risk of lung cancer. Metabolic parameters can be used as biomarkers to provide information independent of the clinical parameters, related to lung cancer risk.

Microwave-Assisted Dendropanax morbifera Extract for Cosmetic Applications.

Recently, utilizing natural bioactive compounds for active ingredients in cosmetics has become a growing worldwide trend. More and more studies aim to identify the sources of herbal ingredients for applications in the pharmaceutical and cosmetic fields. Additionally, in order to optimize the safety of natural ingredients, choosing an environmentally friendly extraction method also plays an important role. In this work, an eco-friendly extraction technique for Dendropanax morbifera using microwave treatment and microwave-assisted Dendropanax morbifera extract (MA-DME) was investigated. The results indicate that higher yields of MA-DME were obtained than with conventional methods and that D. morbifera's antioxidant properties were enhanced. Moreover, we found that MA-DME exhibited extraordinary antioxidant, anti-aging, and skin-whitening activities. We suggest MA-DME as a potential cosmeceutical ingredient than could be utilized for comprehensive protection of human skin.

Comparison of the Characteristics of Asymptomatic and Presymptomatic Patients with Coronavirus Disease 2019 in the Republic of Korea.

PURPOSE: This retrospective study aimed to evaluate the baseline characteristics of asymptomatic patients with coronavirus disease 2019 at admission and to follow-up their clinical manifestations and radiological findings during hospitalization. METHODS: Patients with coronavirus disease 2019 who were asymptomatic at admission were divided into two groups-those with no symptoms until discharge (group A) and those who developed symptoms after admission (group B). Patients who could not express their own symptoms were excluded. RESULTS: Overall, 127 patients were enrolled in the study, of whom 19 and 108 were assigned to groups A and B, respectively. The mean age and median C-reactive protein level were higher in group B than in group A. All patients in group A and one-third of patients in group B had normal initial chest radiographs; 15.8% and 48.1% of patients in groups A and B, respectively, had pneumonia during hospitalization. One patient in group B, whose condition was not severe at the time of admission, deteriorated due to aggravated pneumonia and was transferred to a tertiary hospital. CONCLUSION: We summarize the clinical characteristics during hospitalization of patients with coronavirus disease 2019 who were purely asymptomatic at the time of admission. The majority of asymptomatic patients with coronavirus disease 2019 were discharged without significant events during hospitalization. However, it may be difficult to predict subsequent events from initial chest radiographs or oxygen saturation at admission.

Clinical course of COVID-19 patients treated with ECMO: A multicenter study in Daegu, South Korea.

BACKGROUND: The COVID-19 pandemic has caused an epidemic of critical patients, some of whom have been treated with extracorporeal membrane oxygenation (ECMO). This purpose of study is to describe the clinical course of COVID-19 patients treated with ECMO. METHODS: A multicentered study of critical patients with COVID-19 treated at six hospitals in Daegu was conducted between January and April 2020. RESULTS: Among the 80 patients receiving mechanical ventilation support, 19 (24%) were treated with ECMO included (median age 63.0 years). Eight of the 19 patients (42%) were weaned off ECMO (9.8 days, IQR 7.0-13.7). Among them, four patients were also weaned off mechanical ventilation (33.4 days, IQR 29.3 - 35.7), three were still receiving mechanical ventilation (50.9 days), and one expired after ECMO weaning. According to the univariate analysis, the factor that was associated with successful ECMO weaning was vitamin B12 treatment (p = 0.028). CONCLUSIONS: During the COVID-19 epidemic, ECMO weaning and mortality rates were 42% and 58%, respectively.

Policy Review and Modeling Analysis of Mitigation Measures for Coronavirus Disease Epidemic Control, Health System, and Disease Burden, South Korea.

We reviewed the timeline of key policies for control of the coronavirus disease epidemic and determined their impact on the epidemic and hospital burden in South Korea. Using a discrete stochastic transmission model, we estimated that multilevel policies, including extensive testing, contact tracing, and quarantine, reduced contact rates by 90% and rapidly decreased the epidemic in Daegu and nationwide during February‒March 2020. Absence of these prompt responses could have resulted in a >10-fold increase in infections, hospitalizations, and deaths by May 15, 2020, relative to the status quo. The model suggests that reallocation of persons who have mild or asymptomatic cases to community treatment centers helped avoid overwhelming hospital capacity and enabled healthcare workers to provide care for more severely and critically ill patients in hospital beds and negative-pressure intensive care units. As small outbreaks continue to occur, contact tracing and maintenance of hospital capacity are needed.

Clinical features and prognostic factors of critically ill patients with COVID-19 in Daegu, South Korea: A multi-center retrospective study.

ABSTRACT: To describe the clinical and demographic characteristics of critically ill patients with COVID-19 in Daegu, South Korea, and to explore the risk factors for in-hospital mortality in these patients.Retrospective cohort study of 110 critically ill patients with COVID-19 admitted to the ICU in Daegu, South Korea, between February 18 and April 5, 2020. The final date of follow-up was April 20, 2020.A total of 110 patient medical records were reviewed. The median age was 71 years (interquartile range [IQR] = 63-78 years). During the study period, 47 patients (42.7%) died in the hospital. The most common SARS-CoV-2 infection related complication was acute respiratory distress syndrome (ARDS) in 95 patients (86.4%). Of the 79 patients (71.8%) who received invasive mechanical ventilation, 46 (58.2%) received neuromuscular blockade injection, and 19 (24.1%) received ECMO treatment. All patients received antibiotic injection, 99 patients (90%) received hydroxychloroquine, 96 patients (87.3%) received lopinavir-ritonavir antiviral medication, and 14 patients (12.7%) received other antiviral agents, including darunavir-cobicistat and emtricitabine-tenofovir. In the multivariable logistic regression model, the odds ratio of in-hospital death was higher with APACHE II score (OR = 1.126; 95% CI = 1.014-1.252; P  = .027).The in-hospital mortality rate of critically ill patients with COVID-19 was approximately 40%. Higher APACHE II score at admission was an independent risk factor for death in these patients.

COVID-19: Comparing the applicability of shared room and single room occupancy.

To curb the COVID-19 pandemic, isolation measures are required. Shared room occupancy is recommended when isolation rooms are insufficient. However, there is little evidence of the applicability of shared and single room occupancy for patients with COVID-19 to determine whether shared room occupancy is feasible. COVID-19-infected patients admitted to the Daegu Dongsan Hospital of Keimyung University from 21 February 2020 to 20 April 2020 were enrolled in the study and randomly assigned to hospital rooms. Clinical symptoms, underlying diseases and epidemiological data of patients were analysed after dividing participants into a shared room occupancy group (group A) and a single room occupancy group (group B). Outcomes analysed included microbiological cure rates, time to clinical symptom improvement, time to defervescence and negative-to-positive conversion rates of polymerase chain reaction (PCR) results during hospitalization. A total of 666 patients were included in this study, 535 and 131 patients in groups A and B, respectively. Group B included more underlying conditions, such as pregnancy and solid organ transplantation, and was more closely associated with severe pneumonia during hospitalization. Besides, no statistically significant differences between the two groups in terms of negative PCR rates at HD 7 and 14, conversion rates of PCR results from negative-to-positive, as well as time to the improvement of clinical symptoms, and time to defervescence were observed. Our results suggest that the shared room occupancy of patients with mild symptoms could be an alternative to single room occupancy during the COVID-19 pandemic.

Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality.

Although the lungs are major targets for COVID-19 invasion, other organs-such as the kidneys-are also affected. However, the renal complications of COVID-19 are not yet well explored. This study aimed to identify the incidence of acute kidney injury (AKI) in patients with COVID-19 and to evaluate its impact on patient outcomes. This retrospective study included 704 patients with COVID-19 who were hospitalized at two hospitals in Daegu, Korea from February 19 to March 31, 2020. AKI was defined according to the serum creatinine criteria in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The final date of follow-up was May 1, 2020. Of the 704 patients, 28 (4.0%) developed AKI. Of the 28 patients with AKI, 15 (53.6%) were found to have AKI stage 1, 3 (10.7%) had AKI stage 2, and 10 (35.7%) had AKI stage 3. Among these patients, 12 (42.9%) recovered from AKI. In the patients with AKI, the rates of admission to intensive care unit (ICU), administration of mechanical ventilator (MV), and in-hospital mortality were significantly higher than in patients without AKI. Multivariable analysis revealed that old age (Hazard ratio [HR] = 4.668, 95% confidence interval [CI] = 1.250-17.430, p = 0.022), high neutrophil-to-lymphocyte ratio (HR = 1.167, 95% CI = 1.078-1.264, p < 0.001), elevated creatinine kinase (HR = 1.002, 95% CI = 1.001-1.004, p = 0.007), and severe AKI (HR = 12.199, 95% CI = 4.235-35.141, p < 0.001) were independent risk factors for in-hospital mortality. The Kaplan-Meier curves showed that the cumulative survival rate was lowest in the AKI stage 3 group (p < 0.001). In conclusion, the incidence of AKI in patients with COVID-19 was 4.0%. Severe AKI was associated with in-hospital death.

Lessons from a COVID-19 hospital, Republic of Korea.

OBJECTIVE: To document the experiences of converting a general hospital to a coronavirus disease 2019 (COVID-19) designated hospital during an outbreak in Daegu, Republic of Korea. METHODS: The hospital management formed an emergency task force team, whose role was to organize the COVID-19 hospital. The task force used different collaborative channels to redistribute resources and expertise to the hospital. Leading doctors from the departments of infectious diseases, critical care and pulmonology developed standardized guidelines for treatment coherence. Nurses from the infection control team provided regular training on donning and doffing of personal protective equipment and basic safety measures. FINDINGS: Keimyung University Daegu Dongsan hospital became a red zone hospital for COVID-19 patients on 21 February 2020. As of 29 June 2020, 1048 COVID-19 patients had been admitted to the hospital, of which 22 patients died and five patients were still being treated in the recovery ward. A total of 906 health-care personnel worked in the designated hospital, of whom 402 were regular hospital staff and 504 were dispatched health-care workers. Of these health-care workers, only one dispatched nurse acquired COVID-19. On June 15, the hospital management and Daegu city government decided to reconvert the main building to a general hospital for non-COVID-19 patients, while keeping the additional negative pressure rooms available, in case of resurgence of the disease. CONCLUSION: Centralized coordination in frontline hospital operation, staff management, and patient treatment and placement allowed for successful pooling and utilization of medical resources and manpower during the COVID-19 outbreak.

Intensive Care Unit Capacity and Its Associated Risk Factors During the COVID-19 Surge in the Republic of Korea: Analysis Using Nationwide Health Claims Data.

OBJECTIVE: To identify risk factors for intensive care unit (ICU) admission and mechanical ventilator usage among confirmed coronavirus disease (COVID-19) patients and estimate the effects of mitigation efforts on ICU capacity in Korea. PATIENTS AND METHODS: Data on profiles and medical history of all confirmed COVID-19 patients in the past 1 year were extracted from the Korean National Health Insurance System's claims database to assess risk factors for ICU admission and ventilator use. We used a time-series epidemic model to estimate the ICU census in Daegu from the reported hospital data. FINDINGS: Multivariate regression analysis revealed male sex, old age, and residing in Daegu city as significant risk factors for ICU admission. The number of patients requiring ICU admission exceeded the bed capacity across all Daegu hospitals before March 9, 2020, and therefore, critically ill patients were transferred to nearby hospitals outside Daegu. This finding was consistent with our prediction that the ICU census in Daegu would peak on March 16, 2020, at 160 through mitigation efforts, without which it would have reached 300 by late March 2020. CONCLUSION: Older age and male sex were risk factors for ICU admission. In addition, the geographic location of the hospital seems to contribute to the severity of the COVID-19 patients admitted to the ICU and to the ICU capacity.

The Implication of Cardiac Injury Score on In-hospital Mortality of Coronavirus Disease 2019.

BACKGROUNDS: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. METHODS: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. RESULTS: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). CONCLUSION: The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.

Adverse Initial CT Findings Associated with Poor Prognosis of Coronavirus Disease.

BACKGROUND: The predictors of poor prognosis in patients with coronavirus disease 2019 (COVID-19) using computed tomography (CT) have not been investigated in a large cohort. Therefore, the purpose of this study was to investigate the adverse initial CT features to predict poor prognosis in COVID-19. METHODS: From February to April 2020, 281 COVID-19 patients who underwent CT at the time of admission were included. We divided the patients into the severe and non-severe disease groups. The severe group included patients with severe pneumonia or critical events. Intensive care unit admission or death were the critical events in this study. We compared the clinical and CT findings between the severe and non-severe groups and investigated the prognostic factors and critical events of the severe group using the regression analysis. RESULTS: Among the 281 patients, 36 (12.8%) patients were in the severe group and 245 (87.2%) patients were in the non-severe group. Critical events occurred in 10 patients (3.6%). In the severe group, patients showed significantly more pneumonia with consolidation, crazy-paving appearance, pleural effusion, and higher CT scores than those in the non-severe group (all, P < 0.05). In the multivariate regression, pleural effusion (odds ratio [OR], 8.96; 95% confidence interval [CI], 1.81-44.42; P = 0.007), CT score > 5 (OR, 3.70; 95% CI, 1.44-9.53; P = 0.007), old age (> 77 years, OR, 9.96; 95% CI, 3.78-26.28; P < 0.001), and elevated C-reactive protein (OR, 4.15; 95% CI, 1.62-10.6; P = 0.003) were significant prognostic factors of severe disease. CT score > 5 (OR, 7.29; 95% CI, 1.37-38.68; P = 0.020), pleural effusion (OR, 5.67; 95% CI, 1.04-30.8; P = 0.045) and old age (OR, 8.6; 95% CI, 1.80-41.0; P = 0.007) were also significant predictors of critical events. CONCLUSION: Pleural effusion and the extent of pneumonia on initial CT scans are associated with poor prognosis in patients with COVID-19.

Use of Darunavir-Cobicistat as a Treatment Option for Critically Ill Patients with SARS-CoV-2 Infection.

We retrospectively reviewed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who were admitted to an intensive care unit in Daegu, South Korea. The outcomes of patients who did (cases) or did not (controls) receive darunavir-cobicistat (800-150 mg) therapy were compared. Fourteen patients received darunavir-cobicistat treatment, and 96 received other antiviral therapy (controls). Overall, the darunavir-cobicistat group comprised patients with milder illness, and the crude mortality rate of all patients in the darunavir-cobicistat group was lower than that in the controls [odds ratio (OR) 0.20, 95% confidence interval (CI) 0.04-0.89, p=0.035]. After 1:2 propensity-score matching, there were 14 patients in the darunavir-cobicistat group, and 28 patients in the controls. In propensity score-matched analysis, the darunavir-cobicistat group had lower mortality than the controls (OR 0.07, 95% CI 0.01-0.52, p=0.009). In conclusion, darunavir-cobicistat therapy was found to be associated with a significant survival benefit in critically ill patients with SARS-CoV-2 infection.