Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

Abstract

BACKGROUNDHydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODSWe examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTSOf 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses.

Bepridil is potent against SARS-CoV-2 In Vitro

“…30,31 A likely mechanism of action for hydroxychloroquine is its ability to raise endosomal pH that impacts significantly activities of endosomal proteases that may be required to process the virus membrane proteins. 32,33 Our top three hits pimozide, ebastine, and bepridil are all basic small molecules that can potentiate a similar effect. 34 Among the three drugs, bepridil can be very interesting because it was previously used at a dose of 12 mg/kg for the treatment of Ebola virus infections.…”

Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir

“…For instance, lopinavir/ritonavir (LPV/r) and danoprevir have been proposed to inhibit the SARS-CoV-2 main protease (M pro , also called 3CL Pro ) needed for the maturation of multiple viral proteins; chloroquine (CQ) / hydroxychloroquine (HCQ) [alone or combined with azithromycin (AZ)] may abrogate viral replication by inhibiting endosomal acidification crucial for viral entry (7,8); nucleoside analogues such as remdesivir, ribavirin, favipiravir and EIDD-2801 likely inhibit the SARS-CoV-2 nsp12 RNA-dependent RNA polymerase (RdRP) and/or induce lethal mutations during viral RNA replication (9)(10)(11). Unfortunately, on the clinical aspect, LPV/r failed to demonstrate clinical benefits in well-powered randomized controlled trials (RCTs), while HCQ and/or AZ also failed to demonstrate benefits in observational studies (12)(13)(14). Meanwhile, LPV/r, CQ/HCQ and AZ may even increase the incidence of adverse events (14)(15)(16).…”

Clinical course and challenging management of early COVID-19 infection after heart transplantation: Case report of two patients

“…These two cases illustrate very well the severity and the poor prognosis of COVID-19 infection in the immediate aftermath of a heart transplant. As con rmed by several recent clinical trials [21,22], the antiviral monotherapy with HCQ was ineffective in both cases. We did not observe any toxicity of that drug in both patients.…”