Updating the Novel Therapeutic Interventions in Treating Patients with COVID-19 Pneumonia, COVID-19 Acute Respiratory Syndrome and Severe COVID-19 Illness and Promising Vaccine Candidates

Patients with COVID-19 pneumonia were detected in Wuhan city, China since late December 2019. More and more cases have been identified in other areas outside Wuhan city of China and abroad, particularly in Italy, Iran and other European countries, including the United Kingdom and the United States. Currently, there is no effective treatment for COVID-19-infected patients. Inhibition of pulmonary inflammatory response is hypothesized to be the key to cure the patients with COVID-19 pneumonia. Chloroquine, a potential broad-spectrum antiviral agent found in 2006, can interfere with the virus’s ability to replicate.
Nevertheless, the World Health Organization (WHO) reported that no randomized clinical trials (RCTs) or quasi-experimental studies on the use of chloroquine or hydroxychloroquine on COVID-19 treatment were identified that compared chloroquine to standard care for treatment of COVID-19. There is very low certainty evidence from RCT or quasi-experiment that hydroxychloroquine results in little or no benefit over standard care for treatment of COVID-19. There is also very low certainty evidence of little difference in overall mortality between hydroxychloroquine and standard care. With regards to safety outcomes, there is very certainty evidence that hydroxychloroquine results in more adverse events than standard care. Evidence for other safety outcomes, such as severe adverse events, cardiac arrhythmia, and QT interval prolongation resulting in sudden death was very low certainty. The United States Food and Drug Administration (US FDA) also cautions the use of chloroquine or hydroxychloroquine for COVID-19 outside of the hospital setting or a clinical trial due to the risk of cardiac rhythm problems.
Remdesivir, a nucleoside analogue with a broad-spectrum antiviral activity and as being in the US clinical trials with near approval for use by the US FDA has been also studied in France by Gautretet al from Marseille University. The investigators feel optimistic about the French research data. Previous studies conducted by the researchers from the University of Alberta, Canada and Gilead involving cell cultures and animal models has demonstrated that remdesivir can block the replication of a variety of coronaviruses, hypothesized by blocking the RNA-dependent RNA polymerase, a particular enzyme that is required for viral replication. Remdesivir potently blocks COVID-19 infection at low-micro molar concentration and has a high selectivity index (half-maximal effective concentration (EC50), 0. 77 μM; half-cytotoxic concentration (CC50) > 100 μM; SI > 129. 87). A previous study in the US reported that remdesivir treatment demonstrated promising results. For evaluating the efficacy and safety of remdesivir in patients with COVID-19 disease, a randomized placebo-controlled, double-blind, multicentric phase III clinical trials were initiated on February 5, 2020 in China. The subjects in the study group received a initial dose of 200 mg of remdesivir and a subsequent dose of 100 mg for 9 consecutive days through intravenous infusion in addition to routine treatment. The control group received routine treatment and the same dose of a placebo. By the end of April 2020, the clinical trial is expected to be concluded. Remdesivir was

Author(s): Attapon Cheepsattayakorn and Ruangrong Cheepsattayakorn

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