Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial
Authors: Lauren E Kelly
Sylvain A Lother
Ryan Zarychanski
Nicole W Engen
Ananta S Bangdiwala
Todd C Lee
David R Boulware
Alanna A Nascene
Katelyn A Pastick
Emily G McDonald
Matthew F Pullen
Darlette Luke
Sarah M Lofgren
Kathy H Hullsiek
Radha Rajasingham
Lauren J MacKenzie
Melanie R Nicol
Ilan S Schwartz
Matthew P Cheng
Glen Drobot
Elizabeth C Okafor
Mahsa Abassi
Darlisha A Williams
Caleb P Skipper
Journal: Annals of Internal Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; hydroxychloroquine; severity; outpatient; randomized trial
Affiliations: University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.), Research Institute of the McGill University Health Centre and McGill University, Montréal, Quebec, Canada (M.P.C., E.G.M., T.C.L.), M Health Fairview Investigational Drug Service Pharmacy, Minneapolis, Minnesota (D.L.), University of Manitoba, Winnipeg, Manitoba, Canada (S.A.L., L.J.M., G.D., R.Z.), George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada (L.E.K.), University of Alberta, Edmonton, Alberta, Canada (I.S.S.)

Abstract:  Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients. Design: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668). Setting: Internet-based trial across the United States and Canada (40 states and 3 provinces). Participants: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset. Intervention: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. Measurements: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days. Results: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P &lt; 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29). Limitation: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages. Conclusion: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19. Primary funding source: Private donors. 

Retracted: No

PubPeer comments:
 After adjusting contrast, gel image in Fig.2C showed lots of similarities with image in Fig.3B. Could authors give an explanation? ![file] , 
 ![file] This is Cao-Qi Lei, I am the first author of this paper (doi: 10.1016 j.immuni.2010.11.021). The two adjusted images were performed by Glossosoma Conforme. They look similar but different in some degree, and the differences between them become clearer when the brightness and contrast are further adjusted, as shown above. Unfortunately, we have not been able to locate the original gel data right now. ,