Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture

In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation identified 4 FDA-approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S-protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in the context of drugtreatment. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture.

Outcomes of Mechanically Ventilated Patients with COVID-19 Associated Respiratory Failure

PurposeThe outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system. MethodsOutcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review. Results1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 165 (16.1%) were managed with invasive mechanical ventilation. At the time of data censoring, 63/165 patients (38.1%) had died and 102/165 (61.8%) were still alive. Of the surviving 102 patients, 17 (10.3%) remained on mechanical ventilation, 51 (30.9%) were extubated but remained hospitalized, and 34 (20.6%) had been discharged. Deceased patients were older (median age of 66 vs. 55, p <0.0001). 75.7% of patients over 70 years old had died at the time of data analysis. Conversely, % of patients age 70 or younger were still alive at the time of data analysis. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status. ConclusionMortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.