Chest CT Findings of COVID-19 Patients with Mild Clinical Symptoms at a Single Hospital in Korea.

Purpose: To retrospectively evaluate the chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) in patients with mild clinical symptoms at a single hospital in South Korea. Materials and Methods: CT scans of 87 COVID-19 patients [43 men and 44 women; median age: 41 years (interquartile range: 26.1-51.0 years)] with mild clinical symptoms (fever < 38℃ and no dyspnea) were evaluated. Results: CT findings were normal in 39 (44.8%) and abnormal in 48 (55.2%) patients. Among the 48 patients with lung opacities, 17 (35.4%) had unilateral disease and 31 (64.6%) had bilateral disease. One (2.1%) patient showed subpleural distribution, 9 (18.8%) showed peribronchovascular distribution, and 38 (79.2%) showed subpleural and peribronchovascular distributions. Twenty-two (45.8%) patients had pure ground-glass opacities (GGOs) with no consolidation, 17 (35.4%) had mixed opacities dominated by GGOs, and 9 (18.8%) had mixed opacities dominated by consolidation. No patients demonstrated consolidation without GGOs. Conclusion: The most common CT finding of COVID-19 in patients with mild clinical symptoms was bilateral multiple GGO-dominant lesions with subpleural and peribronchovascular distribution and lower lung predilection. The initial chest CT of almost half of COVID-19 patients with mild clinical symptoms showed no lung parenchymal lesions. Compared to relatively severe cases, mild cases were more likely to manifest as unilateral disease with pure GGOs or GGO-dominant mixed opacities and less likely to show air bronchogram.

High Circulating Levels of Neutrophil Extracellular Traps Parameters Predicting Poor Outcome in COVID-19.

OBJECTIVE: Exploration of biomarkers to predict the severity of COVID-19 is important to reduce mortality. Upon COVID-19 infection, neutrophil extracellular traps (NET) are formed, which leads to a cytokine storm and host damage. Hence, the extent of NET formation may reflect disease progression and predict mortality in COVID-19. METHODS: We measured 4 NET parameters - cell-free double stranded DNA (cell-free dsDNA), neutrophil elastase, citrullinated histone H3 (Cit-H3), and histone - DNA complex - in 188 COVID-19 patients and 20 healthy controls. Survivors (n=166) were hospitalized with or without oxygen supplementation, while non-survivors (n=22) expired during in-hospital treatment. RESULTS: Cell-free dsDNA was significantly elevated in non-survivors in comparison with survivors and controls. The survival rate of patients with high levels of cell-free dsDNA, neutrophil elastase, and Cit-H3 was significantly lower than that of patients with low levels. These three markers significantly correlated with inflammatory markers (absolute neutrophil count and C-reactive protein). CONCLUSION: Since the increase in NET parameters indicates the unfavourable course of COVID-19 infection, patients predisposed to poor outcome can be rapidly managed through risk stratification by using these NET parameters.

Pneumonia-targeted lopinavir/ritonavir-based treatment for patients with COVID-19: an early-period retrospective single center observational study.

BACKGROUND: Robust evidenced treatment strategy for Coronavirus disease 2019 (COVID-19) has not been established yet. Early, targeted, comprehensive management approach can be essential. METHODS: A lopinavir/ritonavir (LPV/r)-based antiviral treatment was administered to the patients with computed tomography (CT)-documented pneumonia. Medical records of patients with COVID-19, previously discharged or hospitalized for ≥ 21 days at the Seoul Medical Center from January 29 to April 15, 2020 were reviewed to analyze clinical and virological outcomes. Patients were divided into two groups (PCR-Negative conversion group vs. Non-negative conversion group and requiring oxygen group vs. Non-requiring oxygen group). RESULTS: In total, 136 patients with a mean age of 41.8 ± 18.2 years were included with median 3-day delay of hospitalization after illness. Thirteen (9.56%) were initially asymptomatic, and 5 (3.67%) were persistently asymptomatic. Eighty-five (62.5%) had CT-documented pneumonia, 94% of whom received LPV/r treatments. A total of 53 patients (38.97%) had negative polymerase chain reaction (PCR) results within 28 days. Eight (9.4%) out of 85 pneumonic patients received oxygen supplementation. Patients with initial lower respiratory symptoms showed significant delay in PCR negative conversion (> 28 days) (odds ratio [OR] 0.166; 95% confidence interval [CI] 0.067-0.477; P < 0.001). However, antiviral treatment for pneumonic patients was significantly related with early conversion within 28 days (OR 3.049; 95% CI 1.128-8.243; P = 0.028). Increasing age increased the likelihood of oxygen supplementation requirement in the pneumonic patient group (OR 1.108; 95% CI 1.021-1.202; P = 0.014). CONCLUSIONS: Early, pneumonia targeted LPV/r-based antiviral therapy resulted in a significantly higher probability of negative conversion of PCR within 28 days compared to symptomatic treatment.

Effects of early corticosteroid use in patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. METHODS: This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. RESULTS: Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. CONCLUSIONS: Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Factors Associated with Worsening Oxygenation in Patients with Non-severe COVID-19 Pneumonia.

BACKGROUND: This study aimed to determine the parameters for worsening oxygenation in non-severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This retrospective cohort study included cases of confirmed COVID-19 pneumonia in a public hospital in South Korea. The worsening oxygenation group was defined as that with SpO2 ≤94% or received oxygen or mechanical ventilation (MV) throughout the clinical course versus the non-worsening oxygenation group that did not experience any respiratory event. Parameters were compared, and the extent of viral pneumonia from an initial chest computed tomography (CT) was calculated using artificial intelligence (AI) and measured visually by a radiologist. RESULTS: We included 136 patients, with 32 (23.5%) patients in the worsening oxygenation group; of whom, two needed MV and one died. Initial vital signs and duration of symptoms showed no difference between the two groups; however, univariate logistic regression analysis revealed that a variety of parameters on admission were associated with an increased risk of a desaturation event. A subset of patients was studied to eliminate potential bias, that ferritin ≥280 µg/L (p=0.029), lactate dehydrogenase ≥240 U/L (p=0.029), pneumonia volume (p=0.021), and extent (p=0.030) by AI, and visual severity scores (p=0.042) were the predictive parameters for worsening oxygenation in a sex-, age-, and comorbid illness-matched case-control study using propensity score (n=52). CONCLUSION: Our study suggests that initial CT evaluated by AI or visual severity scoring as well as serum markers of inflammation on admission are significantly associated with worsening oxygenation in this COVID-19 pneumonia cohort.

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Clinical Experience with Use of Remdesivir in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2: a Case Series.

BACKGROUND: A novel antiviral agent, remdesivir (RDV), is a promising candidate treatment for coronavirus disease 2019 (COVID-19) in the absence of any proven therapy. MATERIALS AND METHODS: This retrospective case series included 10 patients with a clinically and laboratory confirmed diagnosis of severe COVID-19 pneumonia who had received RDV for 5 days (n = 5) or 10 days (n = 5) in the Phase III clinical trial of RDV (GS-US-540-5773) conducted by Gilead Sciences. The clinical and laboratory data for these patients were extracted. RESULTS: One patient in the 10-day group received RDV for only 5 days because of nausea and elevated liver transaminases. No patient had respiratory comorbidity. Seven patients had bilateral lesions and three had unilateral lesions on imaging. All patients had received other medications for COVID-19, including lopinavir/ritonavir and hydroxychloroquine, before administration of RDV. Five patients required supplemental oxygen and one required mechanical ventilation. All patients showed clinical and laboratory evidence of improvement. Half of the patients developed elevated liver transaminases and three had nausea. There were no adverse events exceeding grade 2. CONCLUSION: Our experience indicates that RDV could be a therapeutic option for COVID-19. A well-designed randomized controlled clinical trial is now needed to confirm the efficacy of RDV in patients with COVID-19.

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.

Clinical Experience with Use of Remdesivir in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2: a Case Series

BACKGROUND: A novel antiviral agent, remdesivir (RDV), is a promising candidate treatment for coronavirus disease 2019 (COVID-19) in the absence of any proven therapy. MATERIALS AND METHODS: This retrospective case series included 10 patients with a clinically and laboratory confirmed diagnosis of severe COVID-19 pneumonia who had received RDV for 5 days (n = 5) or 10 days (n = 5) in the Phase III clinical trial of RDV (GS-US-540-5773) conducted by Gilead Sciences. The clinical and laboratory data for these patients were extracted. RESULTS: One patient in the 10-day group received RDV for only 5 days because of nausea and elevated liver transaminases. No patient had respiratory comorbidity. Seven patients had bilateral lesions and three had unilateral lesions on imaging. All patients had received other medications for COVID-19, including lopinavir/ritonavir and hydroxychloroquine, before administration of RDV. Five patients required supplemental oxygen and one required mechanical ventilation. All patients showed clinical and laboratory evidence of improvement. Half of the patients developed elevated liver transaminases and three had nausea. There were no adverse events exceeding grade 2. CONCLUSION: Our experience indicates that RDV could be a therapeutic option for COVID-19. A well-designed randomized controlled clinical trial is now needed to confirm the efficacy of RDV in patients with COVID-19.

Four cases of coronavirus disease 2019 in the early stage of pandemic of South Korea: a single public hospital experience.

In view of this pandemic, as of February 2020, South Korea has the second highest number of confirmed cases in the world. Herein, we report four confirmed coronavirus disease 2019 (COVID-19) cases in the early stage of the pandemic in South Korea and describe the identification, diagnosis, clinical course, and management, including one patient's initial mild symptoms at presentation and their progression to pneumonia on day 21 of illness. Within 48 hours of hospitalization, all four patients underwent evaluation for initial laboratory parameters, COVID-19 polymerase chain reaction (PCR), and chest computed tomography (CT) findings. All four mild COVID-19 patients were discharged, and they were re-examined 14 days after discharge. Despite all four of them being asymptomatic, one patient was re-admitted after confirmation of COVID-19 through PCR viral nucleic acid detection. She could be discharged after 7 days with two subsequent negative COVID-19 PCR at 24-hour intervals. Patients with mild COVID-19 generally have normal follow-up chest CT scans after discharge, even if the early chest CT definitely indicates pneumonia. Re-hospitalized patients with COVID-19 PCR positive results after discharge were not related to her initial chest CT, lab, symptoms compared other three patients.

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.

BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.