Corticosteroid outcome may be dependent of duration of use in severe COVID-19.

BACKGROUND/AIMS: For patients hospitalized with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, the evidence of the optimal duration of corticosteroid is limited. This study aims to identify whether long-term use of corticosteroids is associated with decreased mortality. METHODS: Between February 10, 2020 and October 31, 2021, we analyzed consecutive hospitalized patients with COVID-19 with severe hypoxemia. The patients were divided into short-term (≤ 14 days) and long-term (> 14 days) corticosteroid users. The primary outcome was 60-day mortality. We performed propensity score (PS) analysis to mitigate the effect of confounders and conducted Kaplan-Meier curve analysis. RESULTS: There were 141 (52%) short-term users and 130 (48%) long-term corticosteroid users. The median age was 68 years and the median PaO2/FiO2 at admission was 158. Of the patients, 40.6% required high-flow nasal cannula, 48.3% required mechanical ventilation, and 11.1% required extracorporeal membrane oxygenation. The overall 60-day mortality rate was 23.2%, and that of patients with hospital-acquired pneumonia (HAP) was 22.9%. The Kaplan-Meier curve for 60- day survival in the PS-matched cohort showed that corticosteroid for > 14 days was associated with decreased mortality (p = 0.0033). There were no significant differences in bacteremia and HAP between the groups. An adjusted odds ratio for the risk of 60-day mortality in short-term users was 5.53 (95% confidence interval, 1.90-18.26; p = 0.003). CONCLUSION: For patients with severe COVID-19, long-term use of corticosteroids was associated with decreased mortality, with no increase in nosocomial complications. Corticosteroid use for > 14 days can benefit patients with severe COVID-19.

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

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

Clinical outcomes of and risk factors for secondary infection in patients with severe COVID-19: a multicenter cohort study in South Korea.

Background/Aims: Secondary infection with influenza virus occurs in critically ill patients and is associated with substantial morbidity and mortality; however, there is limited information about it in patients with severe coronavirus disease 2019 (COVID-19). Thus, we investigated the clinical outcomes of and risk factors for secondary infections in patients with severe COVID-19. Methods: This study included patients with severe COVID-19 who were admitted to seven hospitals in South Korea between February 2020 to February 2021. Multivariate logistic regression analyses were performed to assess factors associated with the risk of secondary infections. Results: Of the 348 included patients, 104 (29.9%) had at least one infection. There was no statistically significant difference in the 28-day mortality (17.3% vs. 12.3%, p = 0.214), but in-hospital mortality was higher (29.8% vs. 15.2%, p = 0.002) in the infected group than in the non-infected group. The risk factors for secondary infection were a high frailty scale (odds ratio [OR], 1.314; 95% confidence interval [CI], 1.123 to 1.538; p = 0.001), steroid use (OR, 3.110; 95% CI, 1.164 to 8.309; p = 0.024), and the application of mechanical ventilation (OR, 4.653; 95% CI, 2.533 to 8.547; p < 0.001). Conclusions: In-hospital mortality was more than doubled in patients with severe COVID-19 and secondary infections. A high frailty scale, the use of steroids and application of mechanical ventilation were risk factors for secondary infection.

Impact of COVID-19 Pandemic on Management and Outcomes in Patients with Septic Shock in the Emergency Department.

This study aimed to determine the impact of modifications in emergency department (ED) practices caused by the coronavirus disease 2019 (COVID-19) pandemic on the clinical outcomes and management of patients with septic shock. We performed a retrospective study. Patients with septic shock who presented to the ED between 1 January 2018 and 19 January 2020 were allocated to the pre-COVID-19 group, whereas those who presented between 20 January 2020 and 31 December 2020 were assigned to the post-COVID-19 group. We used propensity score matching to compare the sepsis-related interventions and clinical outcomes. The primary outcome measure was in-hospital mortality. Of the 3697 patients included, 2254 were classified as pre-COVID-19 and 1143 as post-COVID-19. A total of 1140 propensity score-matched pairings were created. Overall, the in-hospital mortality rate was 25.5%, with no statistical difference between the pre- and post-COVID-19 groups (p = 0.92). In a matched cohort, the post-COVID-19 group had delayed lactate measurement, blood culture test, and infection source control (all p < 0.05). There was no significant difference in time to antibiotics (p = 0.19) or vasopressor administration (p = 0.09) between the groups. Although sepsis-related interventions were delayed during the COVID-19 pandemic, there was no significant difference in the in-hospital mortality between the pre- and post-COVID-19 groups.

In-hospital mortality prediction using frailty scale and severity score in elderly patients with severe COVID-19.

BACKGROUND: Elderly patients with coronavirus disease 2019 (COVID-19) have a high disease severity and mortality. However, the use of the frailty scale and severity score to predict in-hospital mortality in the elderly is not well established. Therefore, in this study, we investigated the use of these scores in COVID-19 cases in the elderly. METHODS: This multicenter retrospective study included severe COVID-19 patients admitted to seven hospitals in Republic of Korea from February 2020 to February 2021. We evaluated patients' Acute Physiology and Chronic Health Evaluation (APACHE) II score; confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older (CURB-65) score; modified early warning score (MEWS); Sequential Organ Failure Assessment (SOFA) score; clinical frailty scale (CFS) score; and Charlson comorbidity index (CCI). We evaluated the predictive value using receiver operating characteristic (ROC) curve analysis. RESULTS: The study included 318 elderly patients with severe COVID-19 of whom 237 (74.5%) were survivors and 81 (25.5%) were non-survivors. The non-survivor group was older and had more comorbidities than the survivor group. The CFS, CCI, APACHE II, SOFA, CURB-65, and MEWS scores were higher in the non-survivor group than in the survivor group. When analyzed using the ROC curve, SOFA score showed the best performance in predicting the prognosis of elderly patients (area under the curve=0.766, P<0.001). CFS and SOFA scores were associated with in-hospital mortality in the multivariate analysis. CONCLUSIONS: The SOFA score is an efficient tool for assessing in-hospital mortality in elderly patients with severe COVID-19.

ROX index and SpO2/FiO2 ratio for predicting high-flow nasal cannula failure in hypoxemic COVID-19 patients: A multicenter retrospective study.

BACKGROUND: The ratio of oxygen saturation (ROX) index, defined as the ratio of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate, can help identify patients with hypoxemic respiratory failure at high risk for intubation following high-flow nasal cannula (HFNC) initiation; however, whether it is effective for predicting intubation in coronavirus disease 2019 (COVID-19) patients receiving HFNC remains unknown. Moreover, the SpO2/FiO2 ratio has been assessed as a prognostic marker for acute hypoxemic respiratory failure. This study aimed to determine the utility of the ROX index and the SpO2/FiO2 ratio as predictors of failure in COVID-19 patients who received HFNC. METHODS: This multicenter study was conducted in seven university-affiliated hospitals in Korea. Data of consecutive hospitalized patients diagnosed with COVID-19 between February 10, 2020 and February 28, 2021 were retrospectively reviewed. We calculated the ROX index and the SpO2/FiO2 ratio at 1 h, 4 h, and 12 h after HFNC initiation. The primary outcome was HFNC failure defined as the need for subsequent intubation despite HFNC application. The receiver operating characteristic curve analysis was used to evaluate discrimination of prediction models for HFNC failure. RESULTS: Of 1,565 hospitalized COVID-19 patients, 133 who received HFNC were analyzed. Among them, 63 patients (47.4%) were successfully weaned from HFNC, and 70 (52.6%) were intubated. Among patients with HFNC failure, 32 (45.7%) died. The SpO2/FiO2 ratio at 1 h after HFNC initiation was an important predictor of HFNC failure (AUC 0.762 [0.679-0.846]). The AUCs of SpO2/FiO2 ratio at 4 h and ROX indices at 1 h and 4 h were 0.733 (0.640-0.826), 0.697 (0.597-0.798), and 0.682 (0.583-0.781), respectively. Multivariable analysis showed that the patients aged ≥70 years are 3.4 times more likely to experience HFNC failure than those aged <70 years (HR 3.367 [1.358-8.349], p = 0.009). The SpO2/FiO2 ratio (HR 0.983 [0.972-0.994], p = 0.003) at 1 h was significantly associated with HFNC failure. CONCLUSIONS: The SpO2/FiO2 ratio following HFNC initiation was an acceptable predictor of HFNC failure. The SpO2/FiO2 ratio may be a good prognostic marker for predicting intubation in COVID-9 patients receiving HFNC.

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

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

Lower Driving Pressure and Neuromuscular Blocker Use Are Associated With Decreased Mortality in Patients With COVID-19 ARDS.

BACKGROUND: The impact of mechanical ventilation parameters and management on outcomes of patients with coronavirus disease 2019 (COVID-19) ARDS is unclear. METHODS: This multi-center observational study enrolled consecutive mechanically ventilated patients with COVID-19 ARDS admitted to one of 7 Korean ICUs between February 1, 2020-February 28, 2021. Patients who were age < 17 y or had missing ventilation parameters for the first 4 d of mechanical ventilation were excluded. Multivariate logistic regression was used to identify which strategies or ventilation parameters that were independently associated with ICU mortality. RESULTS: Overall, 129 subjects (males, 60%) with a median (interquartile range) age of 69 (62-78) y were included. Neuromuscular blocker (NMB) use and prone positioning were applied to 76% and 16% of subjects, respectively. The ICU mortality rate was 37%. In the multivariate analysis, higher dynamic driving pressure (ΔP) values during the first 4 d of mechanical ventilation were associated with increased mortality (adjusted odds ratio 1.16 [95% CI 1.00-1.33], P = .046). NMB use was associated with decreased mortality (adjusted odds ratio 0.27 [95% CI 0.09-0.81], P = .02). The median tidal volume values during the first 4 d of mechanical ventilation and the ICU mortality rate were significantly lower in the NMB group than in the no NMB group. However, subjects who received NMB for ≥ 6 d (vs < 6 d) had higher ICU mortality rate. CONCLUSIONS: In subjects with COVID-19 ARDS receiving mechanical ventilation, ΔP during the first 4 d of mechanical ventilation was independently associated with mortality. The short-term use of NMB facilitated lung-protective ventilation and was independently associated with decreased mortality.

Comparison of Clinical Characteristics and Outcomes of Younger and Elderly Patients with Severe COVID-19 in Korea: A Retrospective Multicenter Study.

Old age is associated with disease severity and poor prognosis among coronavirus disease 2019 (COVID-19) cases; however, characteristics of elderly patients with severe COVID-19 are limited. We aimed to assess the clinical characteristics and outcomes of patients hospitalized with severe COVID-19 at tertiary care centers in South Korea. This retrospective multicenter study included patients with severe COVID-19 who were admitted at seven hospitals in South Korea from 2 February 2020 to 28 February 2021. The Cox regression analyses were performed to assess factors associated with the in-hospital mortality. Of 488 patients with severe COVID-19, 318 (65.2%) were elderly (≥65 years). The older patient group had more underlying diseases and a higher severity score than the younger patient group. The older patient group had a higher in-hospital mortality rate than the younger patient group (25.5% versus 4.7%, p-value < 0.001). The in-hospital mortality risk factors among patients with severe COVID-19 included age, acute physiology and chronic health evaluation II score, presence of diabetes and chronic obstructive lung disease, high white blood cell count, low neutrophil-lymphocyte ratio and platelet count, do-not-resuscitate order, and treatment with invasive mechanical ventilation. In addition to old age, disease severity and examination results must be considered in treatment decision-making.

COVID-19-related outcomes in immunocompromised patients: A nationwide study in Korea.

BACKGROUND: Given the rapid increased in confirmed coronavirus disease 2019 (COVID-19) and related mortality, it is important to identify vulnerable patients. Immunocompromised status is considered a risk factor for developing severe COVID-19. We aimed to determine whether immunocompromised patients with COVID-19 have an increased risk of mortality. METHOD: The groups' baseline characteristics were balanced using a propensity score-based inverse probability of treatment weighting approach. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for the risks of in-hospital mortality and other outcomes according to immunocompromised status using a multivariable logistic regression model. We identified immunocompromised status based on a diagnosis of malignancy or HIV/AIDS, having undergone organ transplantation within 3 years, prescriptions for corticosteroids or oral immunosuppressants for ≥30 days, and at least one prescription for non-oral immunosuppressants during the last year. RESULTS: The 6,435 COVID-19 patients (≥18 years) included 871 immunocompromised (13.5%) and 5,564 non-immunocompromised (86.5%). Immunocompromised COVID-19 patients were older (60.1±16.4 years vs. 47.1±18.7 years, absolute standardized mean difference: 0.738). The immunocompromised group had more comorbidities, a higher Charlson comorbidity index, and a higher in-hospital mortality rate (9.6% vs. 2.3%; p < .001). The immunocompromised group still had a significantly higher in-hospital mortality rate after inverse probability of treatment weighting (6.4% vs. 2.0%, p < .001). Multivariable analysis adjusted for baseline imbalances revealed that immunocompromised status was independently associated with a higher risk of mortality among COVID-19 patients (adjusted odds ratio [aOR]: 2.09, 95% CI: 1.62-2.68, p < .001). CONCLUSIONS: Immunocompromised status among COVID-19 patients was associated with a significantly increased risk of mortality.

Late Failure of High-Flow Nasal Cannula May Be Associated with High Mortality in COVID-19 Patients: A Multicenter Retrospective Study in the Republic of Korea.

The aim of this study was to determine whether the late failure of high-flow nasal cannula (HFNC) is associated with mortality in patients with coronavirus disease 2019 (COVID-19). This multicenter study included seven university-affiliated hospitals in the Republic of Korea. We collected the data of patients hospitalized with COVID-19 between 10 February 2020 and 28 February 2021. Failure of HFNC was defined as the need for mechanical ventilation despite HFNC application. According to the time of intubation, HFNC failure was divided into early failure (within 48 h) and late failure (after 48 h). During the study period, 157 patients received HFNC and 133 were eligible. Among them, 70 received mechanical ventilation. The median time from HFNC initiation to intubation of the early failure group was 4.1 h (interquartile range [IQR]: 1.1-13.5 h), and that of the late failure group was 70.9 h (IQR: 54.4-145.4 h). Although the ratio of pulse oximetry/fraction of inspired oxygen (ROX index) within 24 h of HFNC initiation tended to be lower in the early failure group than in the late failure group, the ROX index before two hours of intubation was significantly lower in the late failure group (odds ratio [OR], 5.74 [IQR: 4.58-6.98] vs. 4.80 [IQR: 3.67-5.97], p = 0.040). The late failure of HFNC may be associated with high mortality in COVID-19 patients with acute respiratory failure.

Biomarkers Associated with Failure of Liberation from Oxygen Therapy in Severe COVID-19: A Pilot Study.

This study aimed to investigate whether clinical and laboratory biomarkers can identify patients with COVID-19 who are less likely to be liberated from oxygen therapy. This was a retrospective study comparing 18 patients in the weaning failure group with 38 patients in the weaning success group. Weaning failure was defined as death or discharge with an oxygen device before day 28 after hospital admission or requiring oxygen support as of day 28. The median quick Sequential Organ Failure Assessment (qSOFA) score was significantly higher and the median SpO2/FiO2 was significantly lower in the weaning failure group. The laboratory biomarkers, procalcitonin (PCT) and D-dimer, were significantly higher in the weaning failure group, as were the biomarkers of endothelial injury, such as angiopoietin-2 (Ang-2) and Ang-2/Ang-1, and tumor necrosis factor-α (TNF-α). Patients' qSOFA scores, SpO2/FiO2, and PCT, D-dimer, Ang-2, Ang-2/Ang-1, endocan (4-day and 7-day increases), and TNF-α levels predicted weaning failure; 7-day endocan levels were the best predictor of weaning failure with an AUC of 0.81 (95% CI, 0.67-0.94). We identified clinical and laboratory parameters, including plasma biomarkers of endothelial injury, that may be considered as biomarkers for predicting failure of liberation from oxygen therapy in patients with severe COVID-19.

Dexamethasone may improve severe COVID-19 via ameliorating endothelial injury and inflammation: A preliminary pilot study.

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.

Risk factors associated with the need for oxygen therapy in patients with COVID-19.

ABSTRACT: Respiratory failure is the major cause of death in patients with coronavirus disease (COVID-19). Data on factors affecting the need for oxygen therapy in early-stage COVID-19 are limited. This study aimed to evaluate the factors associated with the need for oxygen therapy in patients with COVID-19.This is a retrospective study of consecutive COVID-19 patients who were hospitalized between February 27 and June 28, 2020, in South Korea. Logistic regression analyses were performed to identify the factors associated with the need for oxygen therapy.Of the 265 patients included in the study, 26 (9.8%) received oxygen therapy, and 7 of these patients (29.2%) were transferred to a step-up facility, and 3 (11.5%) died. The median age of all patients was 46 years (IQR, 30-60 years), and the median modified early warning score at admission was 1 (IQR, 1-2). In a multivariate logistic regression analysis, being a current smoker (odds ratio [OR] 7.641, 95% confidence interval [CI] 1.686-34.630, P = .008), heart rate (OR 1.053, 95% CI 1.010-1.097, P = .014), aspartate aminotransferase values (OR 1.049, 95% CI 1.008-1.092, P = .020), blood urea nitrogen levels (OR 1.171, 95% CI 1.073-1.278, P < .001), and chest radiographic findings (OR 3.173, 95% CI 1.870-5.382, P < .001) were associated with oxygen therapy.In patients with less severe COVID-19, the need for oxygen therapy is affected by smoking and elevated values of aspartate aminotransferase and blood urea nitrogen. Further research is warranted on the risk factors for deterioration in COVID-19 to efficiently allocate medical resources.

Frequency of putative enteric zoster diagnosed using saliva samples in patients with abdominal pain: a prospective study.

BACKGROUND: Varicella-zoster virus (VZV) infects and establishes latency in neurons in the ganglia of the cranial nerve, dorsal root and enteric ganglia. VZV reactivation in enteric neurons (enteric zoster) can cause non-specific abdominal pain and/or serious gastrointestinal dysfunction without cutaneous manifestations. Detection of VZV DNA in saliva may be useful for identifying enteric zoster. We evaluated the frequency of putative enteric zoster based on the presence of salivary VZV DNA in patients with acute abdominal pain. METHODS: Adult patients who visited the emergency room due to moderate to severe acute abdominal pain were prospectively enrolled at a tertiary hospital between May 2019 and November 2019. Abdominopelvic computed tomography (APCT) was performed in all patients. We also evaluated the presence of salivary VZV DNA in patients with confirmed coronavirus disease-19 (COVID-19) who were under stressful conditions. Saliva samples were collected from all studied patients. Enteric zoster was suspected based on the presence of salivary VZV DNA, detected using real-time polymerase chain reaction (PCR). RESULTS: Fifty patients with moderate to severe abdominal pain were enrolled. Five of 50 patients exhibited positive VZV-DNA PCR results. APCT revealed that among these five patients, two had pancreatic head cancer, two had small bowel obstruction after intra-abdominal surgery, and one had no remarkable findings. However, all 14 patients with COVID-19 showed negative salivary VZV-DNA PCR results. CONCLUSIONS: Approximately 10% of patients with moderate to severe acute abdominal pain showed positivity for salivary VZV DNA. Further studies are warranted on whether antiviral therapy based on salivary VZV-DNA PCR results may relieve abdominal pain in the studied patient population. TRIAL REGISTRATION: clinicaltrial.gov, number NCT03862092.

Association of Renin-angiotensin-aldosterone System Inhibitors With Coronavirus Disease 2019 (COVID-19)- Related Outcomes in Korea: A Nationwide Population-based Cohort Study.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors may facilitate host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or attenuate organ injury via RAAS blockade. We aimed to assess the associations between prior use of RAAS inhibitors and clinical outcomes among Korean patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide population-based cohort study using the Korean Health Insurance Review and Assessment database. Claim records were screened for 69 793 individuals who were tested for COVID-19 until 8 April 2020. Adjusted odds ratios (ORs) were used to compare the clinical outcomes between RAAS inhibitor users and nonusers. RESULTS: Among 5179 confirmed COVID-19 cases, 762 patients were RAAS inhibitor users and 4417 patients were nonusers. Relative to nonusers, RAAS inhibitor users were more likely to be older, male, and have comorbidities. Among 1954 hospitalized patients with COVID-19, 377 patients were RAAS inhibitor users, and 1577 patients were nonusers. In-hospital mortality was observed for 33 RAAS inhibitor users (9%) and 51 nonusers (3%) (P < .001). However, after adjustment for age, sex, Charlson comorbidity index, immunosuppression, and hospital type, the use of RAAS inhibitors was not associated with a higher risk of mortality (adjusted OR, 0.88; 95% confidence interval, 0.53-1.44; P = .60). No significant differences were observed between RAAS inhibitor users and nonusers in terms of vasopressor use, modes of ventilation, extracorporeal membrane oxygenation, renal replacement therapy, and acute cardiac events. CONCLUSIONS: Our findings suggest that prior use of RAAS inhibitors was not independently associated with mortality among COVID-19 patients in Korea.