PMC:7441788 / 23288-28508 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7441788","sourcedb":"PMC","sourceid":"7441788","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7441788","text":"Several trials evaluated the efficacy of HCQ for the treatment of COVID-19 (Table 1). In a randomized clinical trial from Wuhan about HCQ treatment of mild COVID-19 [50], 31 out of 62 patients received HCQ (200 mg/2 times/day for 5 days). The results showed that the temperature recovery time in the HCQ group was improved compared with the control group (average days, 2.2 vs. 3.2); the cough relief time was shorter in the HCQ group than the control group (average days, 2.4 vs. 3.1); and the improvement rate of pneumonia in the HCQ group was higher than the control group (80.6% vs. 54.8%). However, only 48% of patients (15/31) in HCQ group and 71% of patients (22/31) in control group had cough at baseline and the duration of cough was not described. Improvement of symptoms were small and the trial was terminated prematurely. These factors and the low sample size compromise the reliability of the results of this study. Importantly, evaluation of HCQ in the COVID-19 pandemic areas have shown that HCQ can help patients with mild symptoms, and may potentially reduce transmission in areas lacking isolation facilities [51,52]. However, in areas with strict isolation standards, the use of HCQ to reduce transmission or for treatment of mild COVID-19 cases may not be beneficial in risk-benefit analysis [51,52]. Nevertheless, there is an urgent need for drugs and therapeutics in severe cases, which require randomized controlled trials. A study from four French tertiary care centers included 181 patients hospitalized for COVID-19 and requiring oxygen (2 L/min): 84 patients received HCQ (600 mg/day) within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group) [53]. The results showed that the patients transferred to the ICU or died within 7 days and developed ARDS within 7 days had no significant differences between the HCQ group and no-HCQ group. Eight patients in the HCQ group (9.5%) discontinued HCQ due to electrocardiogram alterations. These results do not support the use of HCQ for treating hospitalized COVID-19-related hypoxic pneumonia patients. It is worth noting that in the study’s propensity score model, four possible important prognostic variables were unbalanced and a center effect was not considered, which all can cause bias for study results. In a multicenter, randomized, parallel trial about HCQ in patients with mainly mild to moderate COVID-19 [54], 80 patients received ‘standard care’ and 70 patients received HCQ (1200 mg daily for 3 days, and then 800 mg daily for 2 weeks [mild to moderate disease] or 3 weeks [severe disease]). The results showed that the 28-days negative conversion probability in ‘standard care’＋HCQ group was 85.4%, similar to the ‘standard care’ group (81.2%). HCQ did not show additional benefits of viral elimination in patients with mild to moderate COVID-19. However, the study could not evaluate the antiviral effect of HCQ at early stages of disease, which is a critical period of antiviral treatment. In addition, viral RNA specimens were mostly from the upper respiratory tract rather than bronchoalveolar lavage fluid, which may cause false negative results. Due to the small number of severe patients, this study could not provide evidence regarding the effect of HCQ on the disease progression or regression. In another large observational study involving 1376 cases of COVID-19 from New York, 811 patients received HCQ (600 mg/2 times on the first day, then 400 mg once a day for 4 days) within 24 or 48 hours of admission and 565 did not [55]. This study found no correlation between HCQ use and significantly higher or lower risk of intubation or death. However, in this study, even after the propensity score-matching, the diseases in patients receiving HCQ were more severe at baseline than those in the patients not receiving. Notably, according to another recent study [56], low dose of HCQ reduced fatality of critically ill patients with COVID-19 without apparent toxicity. This retrospective study included 550 patients who need mechanical ventilation, of which 48 received HCQ treatment (200 mg/2 times/day for 7 to 10 days) and 502 did not. The fatalities of the HCQ group was significantly lower than no-HCQ group (18.8% vs 47.4%, P \u003c 0.05), and the inflammatory cytokine IL-6 in the HCQ group decreased significantly from 22.2 (8.3 to 118.9 pg/mL) at the beginning of treatment to 5.2 (3.0 to 23.4 pg/mL) at the end of treatment. The authors deemed that the anti-inflammatory effect of low-dose HCQ and the activity of inhibiting viral replication may have important significance in critically ill patients with COVID-19. Yet, this study is flawed due to its retrospective nature and the small number of HCQ treated patients included. In short, some initial studies have shown that HCQ appears to have a curative effect on patients with mild COVID-19, but subsequent studies indicate that HCQ had no significant benefit in COVID-19 patients with viral conversion and the risk of intubation or death. Although some recent studies show that low-dose HCQ could potentially reduce the mortality of severe COVID-19 patients, there are other studies showing that the HCQ use had no effect on risk of intubation or 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