ABSTRACT
Background. Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods. Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI). Results. Of the 61 patients enrolled;41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005). Conclusion. Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels.
ABSTRACT
By the end of 2019 and the initial of 2020, similar symptoms of severe acute respiratory syndrome (SARS) pandemic are presented in China. Extraordinarily, COVID-19 has extensively spread worldwide within the last three months affecting humans' life and causing permanently a fearing sensation among all populations. All agencies worldwide recommended their populations to stay home to prevent and terminate this fatal infectious disease. During exposure to any pandemic infectious disease over history, many modalities of the treatment were reported to control and prevent its prevalence such as improving the public health, rehydration, and vaccinations that became the ideal strategies to exterminate these infectious diseases. No treatment modalities were reported to prevent or control the COVID-19 infection. Therefore, we have to highlight the role of physical therapy and rehabilitation against the outbreak of viral infection. This manuscript suggests that physical therapy and rehabilitation may eliminate the common harmful respiratory, circulatory, and physical complications that follow the exposure to viral infections. Also, it explains that the rehabilitation program may present an effective approach to retrieve physical and psychological functions besides medical treatment. In conclusion, serious recommendations have to be considered for conducting exercise training and telerehabilitation to prevent and control the outbreak of COVID-19.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) emerged as a small outbreak in Wuhan rapidly progressing into the deadliest pandemic since the Spanish flu of 1918. The disease was deemed trivial in children, until the reporting, few days ago, of an emerging pediatric multi-inflammatory syndrome mimicking Kawasaki disease (KD). Main body: This report reveals that coronaviridae were implicated in induction of several post-infectious vasculitides, namely, KD, AHEI, and HSP. This occurs in genetically susceptible individuals to vascular inflammation. Shared genetic susceptibilities between KD and CoV include genes encoding for CD 40, HLAB-15:03, and ACE. This leads to augmented inflammation with hypersecretion of cytokines especially IL-6. Conclusion(s): The revealed relationships between KD and CoV can help to predict the risk of KD in COVID-19 patients through screening levels of upregulated cytokines. It might also signify that classic treatment of KD with IVIG might need to be replaced with anti-cytokine therapy in COVID-19 patients. Copyright © 2020, The Author(s).