PMC:7289100 / 38203-41228 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7289100","sourcedb":"PMC","sourceid":"7289100","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7289100","text":"9 Therapy - using rheumatologic drugs in COVID-19 infection\nMany countries and organizations have published guidelines for treatment of the COVID-19 pandemic. Of note are the Treatment Guidelines of the National Institutes of Health and the American College of Rheumatology guidance for the management of adult patients with rheumatic disease during the COVID-19 pandemic [102,103].\nChloroquine and Hydroxychloroquine, are anti malarial drugs, used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Both chloroquine and hydroxychloroquine (HCQ) have immunomodulatory effects. In general, HCQ has fewer and less severe toxicities (including fewer propensities to prolong the QTc interval) and fewer drug-drug interactions than chloroquine. The proposed mechanisms of action and rationale for use for COVID-19 of both drugs have to do with the increase of the endosomal pH, inhibiting fusion of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the host cell membranes. Furthermore, Chloroquine inhibits glycosylation of the cellular angiotensin-converting enzyme 2 receptor, which may interfere with binding of SARS-CoV to the cell receptor. In vitro, both chloroquine and HCQ may block the transport of SARS-CoV-2 from early endosomes to endolysosomes, which may be required for release of the viral genome, and several studies have demonstrated in vitro activity of chloroquine against SARS-CoV [104,105]. Though HCQ has been administered to patients with Covid-19 there are to date no robust evidence supporting its use. In a retrospective computerized database of 1317 positive subjects for Covid-19 out of a sample size of 14,520, a comparison was conducted between those who tested positive versus those who were found negative, in terms of the rate of administration of HCQ or colchicine. The authors did not find any significant difference in terms of the rates of usage of either drug, thus they concluded that their findings raise doubts regarding the protective role of both these medication in the battle against SARS-CoV-2 infection [106]. Similar results were drawn by a study from a large medical center in New York. The authors examined the association between HCQ use and intubation or death among a group of 1446 consecutive patients. HCQ administration was not associated with either a greatly lowered or an increased risk of intubation or death [107]. Many similar reports came to the same conclusions [[108], [109], [110]], to the extent that the FDA has issued a safety alert and the American College of Physicians has as well recommended against the use of chloroquine or HCQ for COVID-19 [111,112]. Furthermore, an attempt to evaluate HCQ serum or plasma levels from various rheumatic disease patients receiving this treatment, found that these plasma or serum levels were unlikely to achieve the concentration shown to inhibit SARS-CoV-2 in vitro (average target 0.48 mg/L as opposed to the antiviral target of 4/1 mg/L) 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