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1.
Soc Psychiatry Psychiatr Epidemiol ; 2020 Sep 10.
Article in English | MEDLINE | ID: covidwho-754675

ABSTRACT

PURPOSE: This study was conducted to evaluate the status of depression and anxiety of healthcare workers and to explore the risk factors during the outbreak of COVID-19 in China. METHODS: A cross-sectional study was designed using convenience sampling to obtain a sample of healthcare workers. A structured questionnaire was designed to collect the information of the basic characteristics, workload, and the health condition. Burnout, coping style, anxiety, and depression were measured by specific scales. Multiple logistic regression model was performed to explore the risk factors of anxiety or depression. RESULTS: There were 902 questionnaires received between February 9, 2020 and February 11, 2020. The proportion of healthcare workers with symptoms of moderate/severe anxiety and moderate/severe depression were 16.63% and 18.29%, respectively. There were 24.50% healthcare workers experiencing moderate/severe anxiety and depression at the same time. The increased workload, respiratory symptoms, digestive symptoms, having done specific test(s) related to COVID-19, having family member needs to be taken care of, negative coping style, and job burnout were the independent risk factors of anxiety. Furthermore, the increased workload, respiratory symptoms, digestive symptoms, having done specific test(s) related to COVID-19, negative coping style, and job burnout were the independent risk factors of depression. CONCLUSION: More attention should be paid to the mental health of frontline healthcare workers at the outbreak of COVID-19 in China. Taking steps to reduce the intensity of the work and burnout will be effective to stabilize the mental state of them.

2.
J Neurogastroenterol Motil ; 26(3):397-409, 2020.
Article | WHO COVID | ID: covidwho-722244

ABSTRACT

Background/Aims Lipopolysaccharide (LPS) is the key factor inducing mucosal and systemic inflammation in various intestinal and parenteral diseases, which could initially disrupt the epithelial barrier function EphrinA1/ephA2 is speculated to increase the epithelial permeability for its “repulsive interaction” between adjacent cells This study aim to investigate the role of ephrinA1/ephA2 in LPS-induced epithelial hyperpermeability Methods In vivo model challenged with oral LPS in C57BL/6 mice and in vitro model exposed to LPS in Caco2 monolayer were established The barrier function was assessed including expression of tight junction proteins (occludin and claudin-1), transepithelial electrical resistance, and permeability to macromolecules (fluorescein isothiocyanate-labeled fluorescent dextran 4 kDa [FD4]) Moreover, the expression and phosphorylation of ephrinA1/ephA2 were quantified, and its roles in the process of epithelial barrier disruption were confirmed via stimulating ephA2 with ephrinA1-Fc chimera (ephrinA1-Fc) and inactivating ephA2 with ephA2-Fc chimera (ephA2-Fc), or ephA2 monoclonal antibody (ephA2-mab), as well as inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059 Results LPS induced significant barrier dysfunction with dismissed occludin and claudin-1 expression, reduced transepithelial electrical resistance and increased FD4 permeability, accompanied by upregulated ephrinA1/ephA2 pathway and phosphorylation of ephA2 receptor Furthermore, ephA2-Fc, and ephA2-mab ameliorated LPS-induced epithelial hyperpermeability, which was also inhibited by PD98059 Additionally, ephrinA1-Fc led to apparent epithelial leakage in Caco2 monolayer by promoting the phosphorylation of ERK1/2, which could be obviously blocked by ephA2-mab and PD98059 Conclusion EphrinA1/ephA2 promotes epithelial hyperpermeability with an ERK1/2-dependent pathway, which involves in LPS-induced intestinal barrier dysfunction

3.
Scand J Gastroenterol ; 55(9): 1049-1056, 2020 09.
Article in English | MEDLINE | ID: covidwho-694647

ABSTRACT

BACKGROUND AND AIMS: Diarrhea was not uncommon in patients with coronavirus disease 2019 (COVID-19), but the significance remains undetermined. METHODS: This retrospective study included 157 diarrhea cases form 564 hospitalized COVID-19 patients who were admitted to Wuhan Union Hospital from January 20 to February 29, 2020. Clinical characteristics, the course and the outcome of patients with diarrhea were analyzed. The correlation between diarrhea and fecal presence of coronavirus was also determined. RESULTS: The overall morbidity of diarrhea was 27.8% (157/564) in COVID-19 patients. Among them, 38 cases presented only with diarrhea, and 119 cases in both diarrhea and respiratory symptoms. Patients with diarrhea and respiratory symptoms had higher levels of inflammatory activity, longer hospital stay (27.5 vs. 23.0 vs. 22.0 days, p = .029) and higher odds ratio of mortality (3.2 times and 2.2 times, respectively) than those with diarrhea only or respiratory symptoms only. However, patients with diarrhea had longer time from onset to admission (14.5 days vs. 11.0 days, p = .04), higher positive viral RNA in stool (80.0% vs. 52.4%, p = .016) than those with both diarrhea and respiratory symptoms. CONCLUSIONS: Diarrhea caused by high enteric viral burden may lead to long course and poor outcome in COVID-19 patients. The patients with diarrhea and respiratory symptoms were prone to serious condition, and had worse outcomes. However, the patients with diarrhea alone showed mild illness but delayed health-seeking.

4.
J Dig Dis ; 2020 Jul 26.
Article in English | MEDLINE | ID: covidwho-670044

ABSTRACT

OBJECTIVE: Abnormal liver function has been noticed as common extra pulmonary organ damage of the coronavirus disease 2019 (COVID-19). Severe patients had a higher probability and progression of liver injury compared with non-severe patients. We aimed to investigate the prognostic value of liver injury in COVID-19 patients. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazard ratio models were used to find the variables that have an effect on survival. RESULTS: Among enrolled 502 patients, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein (CRP), creatinine, troponin (TnI), D-dimer, lactose dehydrogenase (LDH) and creatine kinase (CK). Compared to patients with normal liver functions, those with abnormal liver functions had higher mortality rate (28.9% vs 9.0%, P<0.001), higher ratio of male patients (65.1% vs 40.8%, P<0.001) and higher chance of SIRS development (53.5% vs 41.3%, P=0.007). Among patients with abnormal liver functions, liver damage grade 2 patients (both ALT/AST and ALP/GGT abnormal) had higher ratio of male patients, neutrophil count, PCT, D-dimer and mortality rate. Multivariate Cox regression analyses suggested that grade of liver damage (HR:1.377, 95%CI:1.000-1.896, P=0.049) was an independent predictor of death. CONCLUSIONS: COVID-19 patients with abnormal liver functions have a higher mortality. Liver damage is an independent prognostic factor of COVID-19. This article is protected by copyright. All rights reserved.

6.
J Gastroenterol Hepatol ; 2020 Jun 29.
Article in English | MEDLINE | ID: covidwho-661233

ABSTRACT

BACKGROUND AND AIM: Dynamic changes of immunocyte subsets and inflammatory profiles in coronavirus disease 2019 (COVID-19) patients with gastrointestinal symptoms were undetermined. METHODS: A single-center retrospective analysis of 409 severe, hospitalized COVID-19 patients from 20 January to 29 February 2020 was performed. The longitudinal characteristics of immune inflammatory cytokines in patients with/without diarrhea were analyzed. The relations of diarrhea and immuno-inflammatory factors with illness course and clinical outcomes were further explored. RESULTS: Diarrhea was more common and more serious with longer duration (4.9 ± 1.5 vs 4.2 ± 1.5 days, P = 0.039) and higher frequency (5.5 ± 2.1 vs 4.0 ± 2.0 times/day, P = 0.001) in deceased patients than in the survivors. Also, diarrhea patients were more inclined to develop multi-organ damage: survivors have longer illness course (media 41.0 vs 36.0 days, P = 0.052) and hospital stays (media 27.0 vs 23.0 days, P = 0.041), and the deceased patients had higher mortality (33.0% vs 22.6%, P = 0.045) and earlier death (media 20.0 vs 25.0 days, P = 0.038). Progressively, neutrophilia and lymphopenia, especially the declined CD8+ T cells, were demonstrated in diarrhea patients relative to the non-diarrhea cases. The inflammatory cytokines including IL-6, IL-10, and TNF-α were intensively increased in patients with diarrhea. The multivariable logistic analysis showed longer duration of diarrhea (P = 0.036), higher neutrophil counts (P = 0.011), and lower lymphocyte counts (P < 0.001) were independent risk factors of in-hospital death. The proportional hazards model indicated that longer duration of diarrhea (P = 0.002), higher frequency of diarrhea (P = 0.058), higher neutrophil counts (P = 0.001), lower lymphocyte counts (P = 0.035), and decreased proportion of CD8+ T cells (P < 0.001) were independently associated with longer illness course of the survivors. CONCLUSIONS: Diarrhea patients were more likely to present with neutrophilia, lymphopenia, and cytokine storm and to develop multi-organ damage. The inflammatory patterns were independent factors associated with illness course of the survivors and in-hospital death of severe COVID-19.

8.
Epidemiol Infect ; 148: e146, 2020 07 07.
Article in English | MEDLINE | ID: covidwho-635047

ABSTRACT

Corona Virus Disease 2019 (COVID-19) has presented an unprecedented challenge to the health-care system across the world. The current study aims to identify the determinants of illness severity of COVID-19 based on ordinal responses. A retrospective cohort of COVID-19 patients from four hospitals in three provinces in China was established, and 598 patients were included from 1 January to 8 March 2020, and divided into moderate, severe and critical illness group. Relative variables were retrieved from electronic medical records. The univariate and multivariate ordinal logistic regression models were fitted to identify the independent predictors of illness severity. The cohort included 400 (66.89%) moderate cases, 85 (14.21%) severe and 113 (18.90%) critical cases, of whom 79 died during hospitalisation as of 28 April. Patients in the age group of 70+ years (OR = 3.419, 95% CI: 1.596-7.323), age of 40-69 years (OR = 1.586, 95% CI: 0.824-3.053), hypertension (OR = 3.372, 95% CI: 2.185-5.202), ALT >50 µ/l (OR = 3.304, 95% CI: 2.107-5.180), cTnI >0.04 ng/ml (OR = 7.464, 95% CI: 4.292-12.980), myohaemoglobin>48.8 ng/ml (OR = 2.214, 95% CI: 1.42-3.453) had greater risk of developing worse severity of illness. The interval between illness onset and diagnosis (OR = 1.056, 95% CI: 1.012-1.101) and interval between illness onset and admission (OR = 1.048, 95% CI: 1.009-1.087) were independent significant predictors of illness severity. Patients of critical illness suffered from inferior survival, as compared with patients in the severe group (HR = 14.309, 95% CI: 5.585-36.659) and in the moderate group (HR = 41.021, 95% CI: 17.588-95.678). Our findings highlight that the identified determinants may help to predict the risk of developing more severe illness among COVID-19 patients and contribute to optimising arrangement of health resources.


Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Blood Cell Count , Blood Chemical Analysis , Child , China/epidemiology , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Electronic Health Records , Female , Humans , Kaplan-Meier Estimate , Kidney Function Tests , Liver Function Tests , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Retrospective Studies , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed , Young Adult
9.
JPEN J Parenter Enteral Nutr ; 2020 Jul 01.
Article in English | MEDLINE | ID: covidwho-624490

ABSTRACT

BACKGROUND: The nutrition status of coronavirus disease 2019 patients is unknown. This study evaluates clinical and nutrition characteristics of severely and critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigates the relationship between nutrition risk and clinical outcomes. METHODS: A retrospective, observational study was conducted at West Campus of Union Hospital in Wuhan. Patients confirmed with SARS-CoV-2 infection by a nucleic acid-positive test and identified as severely or critically ill were enrolled in this study. Clinical data and outcomes information were collected and nutrition risk was assessed using Nutritional Risk Screening 2002 (NRS). RESULTS: In total, 413 patients were enrolled in this study, including 346 severely and 67 critically ill patients. Most patients, especially critically ill patients, had significant changes in nutrition-related parameters and inflammatory markers. As for nutrition risk, the critically ill patients had significantly higher proportion of high NRS scores (P < .001), which were correlated with inflammatory and nutrition-related markers. Among 342 patients with NRS score ≥3, only 84 (of 342, 25%) received nutrition support. Critically ill patients and those with higher NRS score had a higher risk of mortality and longer stay in hospital. In logistic regression models, 1-unit increase in NRS score was associated with the risk of mortality increasing by 1.23 times (adjusted odds ratio, 2.23; 95% CI, 1.10-4.51; P = .026). CONCLUSIONS: Most severely and critically ill patients infected with SARS-CoV-2 are at nutrition risk. The patients with higher nutrition risk have worse outcome and require nutrition therapy.

10.
Hepatology ; 2020 Jun 30.
Article in English | MEDLINE | ID: covidwho-622536

ABSTRACT

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan, China. Although it has been reported that some COVID-19 patients showed elevated liver biochemistries, there are few studies regarding clinical features and prognosis of these patients. In this multicenter, retrospective study, we collected data on laboratory-confirmed COVID-19 patients from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. The data on demographics, comorbidities, clinical symptoms, laboratory examinations on admission, complications, treatment, and outcome were collected. A total of 482 patients were enrolled in this study. Of those, 142 (29.5%) patients showed abnormal liver biochemistries on admission, and patients with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) accounted for 67.6%, 69.0%, and 16.2%, respectively. Those with abnormal liver biochemistries showed higher percentages of severe cases and comorbidities and were more likely to have dyspnea, chest distress or pain, and increased hemoglobin (Hb) on admission. Higher rates of complications and mortality and worse recovery when discharged were observed in patients with abnormal AST or TBIL. The multivariable regression analysis showed that chest distress or pain (odds ratio [OR], 1.765; P = 0.018), dyspnea (OR, 2.495; P = 0.001), elevated C-reactive protein [CRP] level (OR, 1.007; P = 0.008), elevated white blood count (WBC) (OR, 1.139; P = 0.013), and elevated Hb concentration (OR, 1.024; P = 0.001) were independent factors associated with elevated liver biochemistries in COVID-19 patients. Conclusion: Elevated liver biochemistries were common in COVID-19 patients. Patients with hypoxia or severe inflammation are more likely to experience increased liver biochemistries on admission. Those with abnormal AST or TBIL on admission are more likely to suffer from severe complications and death.

11.
Pharmacol Res ; 160: 105036, 2020 Jun 18.
Article in English | MEDLINE | ID: covidwho-603906

ABSTRACT

OBJECTIVES: The current diagnosis and medicines approach in coronavirus disease 2019 (COVID-19) does not reflect the heterogeneous characteristics of this disease. This study aims to find a new antiviral combination regimen by investigating the frequency of clinically relevant and objectively identified comorbidities, and the clustering of these clinical syndromes and varying results of treatment with antiviral drugs in patients hospitalized with severe COVID-19. METHODS: This study recruited 151 severe COVID-19 infection cases diagnosed in our hospital examination and illustrated the clinical potential during a consecutive 25-day medication period. Potential differences in disease severity and clinical characteristics, hematological profile, and current pharmacologic treatments (single agent, double or triple combinations, and the combined antiviral drugs plus Lianhua Qingwen) among comorbidity clusters were explored. RESULTS: Although disease severity was comparable among three clusters, it was markedly different in terms of laboratory test status. Coagulable abnormality was mainly present in cluster 1 and cluster 2. Other indicators were normal, except for a significant increase of neutrophils presented in cluster 2. Patients showed the most complicated haematological results in cluster 3, including severe coagulation abnormalities, leukocytosis, neutrophilic granulocytosis, and lymphopenia. Our results for the first time suggest that a quadruple combination therapy (Ribavirin, Lopinavir/ritonavir, Umifenovir, and Lianhua Qingwen) can be considered as a preferred treatment approach to severe COVID-19 patients. After treatment, abnormal coagulation and leukocyte had markedly improved with a better prognosis. CONCLUSION: This study expands the understanding of the co-occurrence of combination therapy in patients with COVID-19, which provides the probability of developing novel combined therapy. Furthermore, explore clinical trials of variable antivirus treatments based on subgroup analyses or on using subgroups in the selection criteria would be the next step.

12.
Am J Respir Crit Care Med ; 201(11): 1380-1388, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-436947

ABSTRACT

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Adult , Age Factors , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , China/epidemiology , Comorbidity , Coronavirus Infections/mortality , Critical Illness , Female , Hospital Mortality , Humans , Incidence , Lung/pathology , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Pleural Effusion/virology , Pneumonia, Viral/mortality , Tomography, X-Ray Computed
14.
Am J Respir Crit Care Med ; 201(11): 1380-1388, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-47397

ABSTRACT

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Adult , Age Factors , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , China/epidemiology , Comorbidity , Coronavirus Infections/mortality , Critical Illness , Female , Hospital Mortality , Humans , Incidence , Lung/pathology , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Pleural Effusion/virology , Pneumonia, Viral/mortality , Tomography, X-Ray Computed
15.
Open Forum Infect. Dis. ; 3(7): 1-6, 2020.
Article in English | ELSEVIER | ID: covidwho-42928

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly in China. Until now, no definite effective treatment has been identified. We reported on 3 patients with severe COVID-19 who received high-dose intravenous immunoglobulin (IVIg) with satisfactory recovery. Based on these observations, randomized studies of high-dose IVIg should be considered in deteriorating patients infected with COVID-19.

16.
N Engl J Med ; 382(19): 1787-1799, 2020 05 07.
Article in English | MEDLINE | ID: covidwho-9371

ABSTRACT

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/drug therapy , Cytochrome P-450 CYP3A Inhibitors/therapeutic use , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Aged , Antiviral Agents/adverse effects , Betacoronavirus/genetics , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Drug Therapy, Combination , Female , Hospital Mortality , Humans , Intention to Treat Analysis , Lopinavir/adverse effects , Male , Middle Aged , Pandemics , Patient Acuity , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Proportional Hazards Models , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/adverse effects , Time-to-Treatment , Treatment Failure , Viral Load
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