Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147.

Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing drugs against COVID-19. Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP and RNA-IP were used to confirm the regulation of HuR on mRNA of CD147. Regulation of niclosamide on HuR nucleo-translocation was assessed by immunofluorescence staining of cell lines, IHC staining of tissue of mouse model and western blotting. Finally, the suppression of niclosamide on SARS-CoV-2 infection induced CD147 was evaluated by ACE2-expressing A549 cells and western blotting. Results We first discovered a novel regulation mechanism of CD147 via the RNA-binding protein HuR. We found that HuR regulates CD147 post-transcription by directly bound to its 3'-UTR. The loss of HuR reduced CD147 in multiple cell lines. Niclosamide inhibited CD147 function by blocking HuR cytoplasmic translocation and diminishing CD147 glycosylation. SARS-CoV-2 infection induced CD147 in ACE2-expressing A549 cells, which could be neutralized by niclosamide in a dose-dependent manner. Conclusion Together, our study reveals a novel regulation mechanism of CD147 and niclosamide can be repurposed as an effective COVID-19 drug by targeting the virus entry, CD147-spike protein.

Epidemiology of influenza under the coronavirus disease 2019 pandemic in Nanjing, China.

PURPOSE: Since the pandemic of coronavirus disease-19 (COVID-19), the incidence of influenza has decreased significantly, but there are still few reports in the short period before and after the pandemic period. This study aimed to explore influenza activity and dynamic changes before and during the pandemic. METHODS: A total of 1 324 357 influenza-like illness (ILI) cases were reported under the ILI surveillance network from January 1, 2018, to September 5, 2021, in Nanjing, of which 16 158 cases were detected in a laboratory. Differences in ILI and influenza were conducted with the χ2 test. RESULTS: The number of ILI cases accounted for 8.97% of outpatient and emergency department visits. The influenza-positive ratio (IPR) was 7.84% in ILI cases. During the COVID-19 pandemic, ILI% and IPR dropped by 6.03% and 11.83% on average, respectively. Besides this, IPR rose slightly in Week 30-35 of 2021. Not only differences in gender, age, and employment status, but also the circulating strains had changed from type A to B through the COVID-19 pandemic. CONCLUSION: The level of influenza activity was severely affected by COVID-19, but it seems that it is inevitable to be vigilant against the co-circulation in the future.

Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia.

OBJECTIVE: To study chest CT images and clinical characteristics of COVID-19 pneumonia in pregnant patients to examine any correlation. METHODS: Between December 31, 2019 and March 7, 2020, 23 hospitalized pregnant patients with confirmed COVID-19 were enrolled in the study. Clinical presentations were collected retrospectively from records, including laboratory testing, chest CT imaging, and symptoms. Descriptive analysis and correlation of patients' clinical and CT characteristics were performed. Laboratory results from time of first admission and CT absorption (defined as reduction in lesion area, decrease in density, and absorption of some solid components) were compared between symptomatic and asymptomatic patients. RESULTS: Fifteen (65.2%) patients were asymptomatic with patchy ground-glass opacity in a single lung lobe. Eight (34.8%) patients were symptomatic with multiple patchy ground-glass shadows, consolidation, and fibrous stripes. Differences in lymphocyte percentage and neutrophil granulocyte rate between first admission and CT absorption were significant (P<0.001). Median absorption time was shorter in the asymptomatic group compared with the symptomatic group (5 vs 10 days; P<0.001). Median hospitalization time between asymptomatic and symptomatic patients was 14 vs 25.5 days; P>0.001. Median absorption time and length of hospitalization for all patients was 6 days (IQR 5-8) and 17 days (IQR 13-25), respectively. CONCLUSION: Radiological findings and clinical characteristics in pregnant women with COVID-19 were similar to those of non-pregnant women with COVID-19. Median absorption time and length of hospitalization in asymptomatic patients were significantly shorter than in symptomatic patients. Lymphocyte percentage and neutrophil granulocyte rate may be used as laboratory indicators of CT absorption.

Early prediction and identification for severe patients during the pandemic of COVID-19: A severe COVID-19 risk model constructed by multivariate logistic regression analysis.

BACKGROUND: As an emergent and fulminant infectious disease, Corona Virus Disease 2019 (COVID-19) has caused a worldwide pandemic. The early identification and timely treatment of severe patients are crucial to reducing the mortality of COVID-19. This study aimed to investigate the clinical characteristics and early predictors for severe COVID-19, and to establish a prediction model for the identification and triage of severe patients. METHODS: All confirmed patients with COVID-19 admitted by the Second Affiliated Hospital of Air Force Medical University were enrolled in this retrospective non-interventional study. The patients were divided into a mild group and a severe group, and the clinical data were compared between the two groups. Univariate and multivariate analysis were used to identify the independent early predictors for severe COVID-19, and the prediction model was constructed by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model and each early predictor. RESULTS: A total of 40 patients were enrolled in this study, of whom 19 were mild and 21 were severe. The proportions of patients with venerable age (≥60 years old), comorbidities, and hypertension in severe patients were higher than that of the mild (P < 0.05). The duration of fever and respiratory symptoms, and the interval from illness onset to viral clearance were longer in severe patients (P < 0.05). Most patients received at least one form of oxygen treatments, while severe patients required more mechanical ventilation (P < 0.05). Univariate and multivariate analysis showed that venerable age, hypertension, lymphopenia, hypoalbuminemia and elevated neutrophil lymphocyte ratio (NLR) were the independent high-risk factors for severe COVID-19. ROC curves demonstrated significant predictive value of age, lymphocyte count, albumin and NLR for severe COVID-19. The sensitivity and specificity of the newly constructed prediction model for predicting severe COVID-19 was 90.5% and 84.2%, respectively, and whose positive predictive value, negative predictive value and crude agreement were all over 85%. CONCLUSIONS: The severe COVID-19 risk model might help clinicians quickly identify severe patients at an early stage and timely take optimal therapeutic schedule for them.

Characteristics of Acute Pulmonary Embolism in Patients With COVID-19 Associated Pneumonia From the City of Wuhan.

The aim of this study was to describe clinical, imaging, and laboratory features of acute pulmonary embolism (APE) in patients with COVID-19 associated pneumonia. Patients with COVID-19 associated pneumonia who underwent a computed tomography pulmonary artery (CTPA) scan for suspected APE were retrospectively studied. Laboratory data and CTPA images were collected. Imaging characteristics were analyzed descriptively. Laboratory data were analyzed and compared between patients with and without APE. A series of 25 COVID-19 patients who underwent CTPA between January 2020 and February 2020 were enrolled. The median D-dimer level founded in these 25 patients was 6.06 µg/mL (interquartile range [IQR] 1.90-14.31 µg/mL). Ten (40%) patients with APE had a significantly higher level of D-dimer (median, 11.07 µg/mL; IQR, 7.12-21.66 vs median, 2.44 µg/mL; IQR, 1.68-8.34, respectively, P = .003), compared with the 15 (60%) patients without APE. No significant differences in other laboratory data were found between patients with and without APE. Among the 10 patients with APE, 6 (60%) had a bilateral pulmonary embolism, while 4 had a unilateral embolism. The thrombus-prone sites were the right lower lobe (70%), the left upper lobe (60%), both upper lobe (40%) and the right middle lobe (20%). The thrombus was partially or completely absorbed after anticoagulant therapy in 3 patients who underwent a follow-up CTPA. Patients with COVID-19 associated pneumonia have a risk of developing APE during the disease. When the D-dimer level abnormally increases in patients with COVID-19 pneumonia, CTPA should be performed to detect and assess the severity of APE.