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1.
BMC Infect Dis ; 21(1): 952, 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-1412791

ABSTRACT

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.


Subject(s)
COVID-19 , Pneumonia , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Combinations , Humans , Infant, Newborn , Lopinavir/therapeutic use , Pneumonia/drug therapy , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2
2.
BMC Infect Dis ; 21(1): 952, 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-1406709

ABSTRACT

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.


Subject(s)
COVID-19 , Pneumonia , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Combinations , Humans , Infant, Newborn , Lopinavir/therapeutic use , Pneumonia/drug therapy , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2
3.
Clin Infect Dis ; 73(3): e550-e558, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338090

ABSTRACT

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Animals , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/drug therapy , Humans , Mice , Republic of Korea , Spike Glycoprotein, Coronavirus
4.
Clin Microbiol Infect ; 2021 Jun 14.
Article in English | MEDLINE | ID: covidwho-1312375

ABSTRACT

OBJECTIVES: We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients. METHODS: We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens. RESULTS: The seropositivity rate persisted for up to 4 years (50.7-56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT50, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection. DISCUSSION: The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.

5.
Tuberc Respir Dis (Seoul) ; 84(2): 115-124, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1159662

ABSTRACT

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.

6.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1065202

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
7.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-988082

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
8.
Infect Chemother ; 52(3): 369-380, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-918286

ABSTRACT

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.

9.
Infection & chemotherapy ; 2020.
Article in English | WHO COVID | ID: covidwho-696075

ABSTRACT

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.

10.
Korean J Intern Med ; 35(4): 788-792, 2020 07.
Article in English | MEDLINE | ID: covidwho-646087

ABSTRACT

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.


Subject(s)
Coronavirus Infections/diagnostic imaging , Lopinavir/therapeutic use , Pneumonia, Viral/diagnostic imaging , Ritonavir/therapeutic use , Adult , COVID-19 , Coronavirus Infections/drug therapy , Drug Combinations , Female , Humans , Male , Pandemics , Pneumonia, Viral/drug therapy , Radiography, Thoracic
11.
J Korean Med Sci ; 35(13): e142, 2020 Apr 06.
Article in English | MEDLINE | ID: covidwho-31389

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adult , Aged , Asymptomatic Diseases , C-Reactive Protein/analysis , COVID-19 , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Cough/etiology , Diarrhea/etiology , Fever/etiology , Humans , Lymphopenia/etiology , Male , Middle Aged , Oxygen Inhalation Therapy , Pharyngitis/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prodromal Symptoms , Radiography, Thoracic , Real-Time Polymerase Chain Reaction , Republic of Korea , Retrospective Studies , SARS-CoV-2 , Time Factors , Tomography, X-Ray Computed , Young Adult
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