ABSTRACT
While most of the infected develop symptoms only mild (40%) to moderate (40%) in severity, approximately 15% develop severe disease that requires oxygen support, and 5% are critical with complications such as respiratory failure, acute respiratory distress syndrome (ARDS), sepsis and septic shock, thromboembolism, and/or multiorgan failure, including acute kidney injury and cardiac injury [1]. Agarwal et al, attempt to summarize and analyze results from published trials and note that many if not all of the overviewed studies have limitations that may influence the interpretation of results [10]. [...]we aimed to review available data for the application of HCQ as a chemoprophylactic agent for COVID-19, outline weakness of published trials and assess the objectivity of conclusions regarding the possible benefits of HCQ prophylaxis against the novel coronavirus disease. Extracted data encompassed author and date, type of study, type of exposure, dosage regimen used and period of intake, subject population and control group(s), number of occurring infections in test and control groups and authors' conclusions. First of all, the trial was terminated prematurely without reaching the prespecified sample size, therefore not reaching the necessary statistical power.
ABSTRACT
Mortality rates of COVID-19 Case fatality rate from COVID-19 is calculated as a ratio of total deaths to total number of cases for each country as provided by the website of Worldometer (https://www.worldometers.info/ coronavirus/) on the 10 July 2020 (date of site access) for the 56 countries with the largest number of registered cases (above 10 000). The hypothesis that two groups that the mortality rate in two independent groups of countries: those with > 50% increase in use of hydroxychloroquine and these with < 50% increase in use of hydroxychloroquine do not differ was tested by Student's t-test. Mortality rate from COVID-19 was extrapolated as a case fatality rate from data about total deaths to total number of registered cases for each country as provided by the website of Worldometer. In an attempt to determine the existence of a linear relation between changes in hydroxychloroquine use and mortality rate from COVID-19 we performed a correlation analysis.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn't confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.