Table 1.
Timeline of major worldwide developments related to use of HCQS for the management of COVID-19.
| Date | Event | In text references |
|---|---|---|
| March 9, 2020 | Yao et al., demonstrate the efficacy of HCQS in an invitro study using SARS-CoV-2 infected vero-cells | Yao et al. (2020) |
| March 20, 2020 | First clinical study conducted by Gautret et al. on twenty-two patients concluded that adding azithromycin to HCQS has synergistic effect against SARS-CoV-2 infection | Gautret et al. (2020a) |
| March 21, 2020 | U.S President endorses HCQS by calling it a ‘game changer’ for COVID-19 treatment | President's Tweet (2020) |
| March 22, 2020 | ICMR recommends the prophylactic use of HCQS for healthcare providers & close contacts of COVID-19 patients | Advisory on the Empiric (2020) |
| March 28, 2020 | FDA allows emergency off-label use of HCQS and CQ for the treatment of seriously ill COVID-19 patients. | Lenzer (2020) |
| March 31, 2020 | Data from first RCT conducted in Wuhan using HCQS against COVID-19 were posted on MedRxiv.org | Chen J et al., (2020) |
| April 3, 2020 | Concerns are raised regarding the conduct and reporting of the study by Gautret et al. and International Society of Anti-microbial Chemotherapy (ISAC) released an official statement sharing their concern. | Joint ISAC and Elsevier Statement on Gautret et al. (2020a) |
| April 3, 2020 | American Thoracic Society suggests the use of HCQS in hospital admitted patients with COVID-19 pneumonia | COVID-19: Interim Guidance (2020) |
| April 11, 2020 | Infectious Disease Society of America (IDSA) recommends the use of HCQS & azithromycin in COVID-19 patients preferably in clinical trial settings. | Infectious Diseases Society of America Guidelines (2020) |
| April 24, 2020 | FDA cautions against the use of HCQS outside the ambit of clinical trials/hospitals due to safety concerns like cardiac arrhythmia | FDA (2020b) |
| May 22, 2020 | Mehra et al. publish a multinational registry analysis involving 96,000 patients and conclude that no beneficial effect of HCQS was observed with or without azithromycin in COVID-19. Treatment was associated with reduced survival and an increased frequency of ventricular arrhythmias. | Mehra et al. (2020a) |
| May 22, 2020 | ICMR expanded the prophylactic use of HCQS for asymptomatic healthcare providers as well as frontline COVID-19 workers. | Revised Advisory (2020) |
| May 25 | WHO suspends the HCQS arm in SOLIDARITY trial in COVID-19 patients following the paper published by Mehra et al. citing need for review of safety concerns | WHO Suspends Hydroxychloroquine Study (2020) |
| June 3, 2020 | Lancet editors express concerns over the questions raised about the validity of the study by Mehra et al. | Editors (2020) |
| June 5, 2020 | Lancet retracts the paper by Mehra et al. following authors' request. | Mehra et al. (2020b) |
| June 5, 2020 | WHO resumed HCQS arm in the SOLIDARITY trial following an independent review of the interim data | WHO Resumes Study (2020) |
| June 5, 2020 | RECOVERY trial investigators decide to halt enrolment into the HCQS arm based on an unblinded analysis of the data from treated individuals. | Statement from the Chief Investigators (2020) |
| June 15, 2020 | FDA revokes emergency use authorization of HCQS and CQ in COVID-19 as it concludes that the drug is unlikely to be effective and potential risks outweigh the potential benefits. | Coronavirus (COVID-19) Update (2020) |
| June 17, 2020 | WHO announces the stoppage of HCQS arm enrollment in the SOLIDARITY trial following review of available data and concludes that HCQS doesn't reduce COVID-19 related mortality? | WHO Halts Trial (2020) |
Abbreviations: HCQS-Hydroxychloroquine, CQ-Chloroquine, SARS-CoV-2- severe acute respiratory syndrome coronavirus 2, COVID-19- Coronavirus disease 2019, FDA- Food and Drug Administration, ICMR-Indian Council of Medical Research, WHO-World Health Organization, RCT-Randomized controlled trial.