A trial of arbidol hydrochloride in adults with COVID-19.

BACKGROUND: To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. METHODS: This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. RESULTS: A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P  = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. CONCLUSIONS: SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week anas, accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1.

Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among all known SARS-CoV-2 variants. Our structural studies revealed that CTSL cleavage promoted S to adopt receptor-binding domain (RBD) "up" activated conformations, facilitating receptor-binding and membrane fusion. We confirmed that CTSL cleavage is essential during infection of all emerged SARS-CoV-2 variants (including the recently emerged Omicron variant) by pseudovirus (PsV) infection experiment. Furthermore, we found CTSL-specific inhibitors not only blocked infection of PsV/live virus in cells but also reduced live virus infection of ex vivo lung tissues of both human donors and human ACE2-transgenic mice. Finally, we showed that two CTSL-specific inhibitors exhibited excellent In vivo effects to prevent live virus infection in human ACE2-transgenic mice. Our work demonstrated that inhibition of CTSL cleavage of SARS-CoV-2 S protein is a promising approach for the development of future mutation-resistant therapy.

Quantitative Analysis of Pleural Line and B-Lines in Lung Ultrasound Images for Severity Assessment of COVID-19 Pneumonia.

Specific patterns of lung ultrasound (LUS) images are used to assess the severity of coronavirus disease 2019 (COVID-19) pneumonia, while such assessment is mainly based on clinicians' qualitative and subjective observations. In this study, we quantitatively analyze the LUS images to assess the severity of COVID-19 pneumonia by characterizing the patterns related to the pleural line (PL) and B-lines (BLs). Twenty-seven patients with COVID-19 pneumonia, including 13 moderate cases, seven severe cases, and seven critical cases, are enrolled. Features related to the PL, including the thickness (TPL) and roughness of the PL (RPL), and the mean (MPLI) and standard deviation (SDPLI) of the PL intensities are extracted from the LUS images. Features related to the BLs, including the number (NBL), accumulated width (AWBL), attenuation coefficient (ACBL), and accumulated intensity (AIBL) of BLs, are also extracted. The correlations of these features with the disease severity are evaluated. The performances of the binary severe/non-severe classification are assessed for each feature and support vector machine (SVM) classifiers with various combinations of features as input. Several features, including the RPL, NBL, AWBL, and AIBL, show significant correlations with disease severity (all ). The classification performance is optimal using the SVM classifier using all the features as input (area under the receiver operating characteristic (ROC) curve = 0.96, sensitivity = 0.93, and specificity = 1). These findings demonstrate that the proposed method may be a promising tool for automatic grading diagnosis and follow-up of patients with COVID-19 pneumonia.

Erratum to "Clinical Characteristics of Diabetic Patients with COVID-19".

[This corrects the article DOI: 10.1155/2020/1652403.].

Clinical Characteristics of Diabetic Patients with COVID-19.

BACKGROUND: Since December 2019, novel coronavirus- (SARS-CoV-2) infected pneumonia (COVID-19) has rapidly spread throughout China. This study is aimed at describing the characteristics of COVID-19 patients in Wuhan. METHODS: 199 COVID-19 patients were admitted to Wuhan Red Cross Hospital in China from January 24th to March 15th. The cases were divided into diabetic and nondiabetic groups according to the history of taking antidiabetic drugs or by plasma fasting blood glucose level at admission, and the difference between groups were compared. RESULTS: Among 199 COVID-19 patients, 76 were diabetic and 123 were nondiabetic. Compared with nondiabetics, patients with diabetes had an older age, high levels of fasting plasma glucose (FPG), D-dimer, white blood cell, blood urea nitrogen (BUN) and total bilirubin (TBIL), lower levels of lymphocyte, albumin and oxygen saturation (SaO2), and higher mortality (P < 0.05). The two groups showed no difference in clinical symptoms. Diabetes, higher level of D-dimer at admission, and lymphocyte count less than 0.6 × 109/L at admission were associated with increasing odds of death. Antidiabetic drugs were associated with decreasing odds of death. Treatment with low molecular weight heparin was not related to odds of death. CONCLUSION: The mortality rate of COVID-19 patients with diabetes was significantly higher than those without diabetes. Diabetes, higher level of D-dimer, and lymphocyte count less than 0.6 × 109/L at admission were the risk factors associated with in-hospital death.

Apparent and occult infections of medical staff in a COVID-19 designated hospital.

Since the outbreak of novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19), numerous medical staff are fighting on the frontline. However, the possibility of occult infection in medical staff is ignored in many recent studies. Herein, we collected data in a COVID-19 designated hospital from January 22, 2020 to March 10, 2020. A total of 33 medical staff had at least one nucleic acid test of throat swab, immunoglobulin G (IgG) or IgM serum antibody test, and chest computed tomography (CT), were enrolled. Finally, we identified 25 cases (75.8%) were isolated for hospitalized treatment after positive virus detection. In addition, 4 cases who were all negative for nucleic acid test detection with no clinical symptoms, and none of their chest CT were abnormal. However, the results of serum IgG or IgM antibody test in these 4 cases were positive, suggesting the presence of occult infection. In conclusion, data from our single center indicated that SARS-CoV-2 had a high medical infection rate (29/33 = 87.9%) and might have a potential risk of occult infection.