The Rise and Fall of Chloroquine/Hydroxychloroquine as Compassionate Therapy of COVID-19

Abstract

The emergence and rapid spread of novel coronavirus disease (COVID-19) has posed a serious challenge to global public health in 2020. The speed of this viral spread together with the high mortality rate has caused an unprecedented public health crisis. With no antivirals or vaccines available for the treatment of COVID-19, the medical community is presently exploring repositioning of clinically approved drugs for COVID-19. Chloroquine (CQ) and hydroxychloroquine (HCQ) have emerged as potential candidates for repositioning as anti–COVID-19 therapeutics and have received FDA authorization for compassionate use in COVID-19 patients. On March 28, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for HCQ in the treatment of COVID-19. However, it was later revoked by the FDA on June 15, 2020, after analyzing the emerging scientific data from ongoing clinical trials. Similarly, the World Health Organization (WHO) also conducted a Solidarity trial of chloroquine, hydroxychloroquine, remdesivir, lopinavir, and ritonavir. However, on May 23, 2020, the executive body of the “Solidarity trial” decided to put a temporary hold on the HCQ trial. On June 17, 2020, the WHO abruptly stopped the Solidarity trial of HCQ. The current review strives to examine the basis of compassionate use of CQ and HCQ for the treatment of COVID-19 in terms of literature evidence, establishing the antiviral efficacy of these drugs against corona and related viruses. Furthermore, the review presents a critical analysis of the clinical trial findings and also provides an insight into the dynamically changing decision on the authorization and withdrawal of HCQ as anti–COVID-19 therapy by the U.S. FDA and the WHO. Ultimately, our study necessitates an evidenced-based treatment protocol to confront the ongoing COVID-19 pandemic and not the mere observational study that mislead the public healthcare system, which paralyzes the entire world.

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

“… 281 Chloroquine was first reported to be active against SARS-CoV-2 in vitro in early 2020, which promoted clinical trials and authorization. 264 , 274 , 282 , 283 Later, it faded out of the list of antiviral agents against SARS-CoV-2 with disproved inhibiting infection at the cellular level and protection in clinical practice. 284 – 286 Mpro/3CLpro and PLpro play essential roles in transforming viral polyprotein into an active form in SARS-COV-2 replication.…”

Emerging Therapies for COVID-19: The Value of Information From More Clinical Trials

“…The net value of further trials for hydroxychloroquine outweighed the cost of research, and therefore, the highest net value for this drug was found in the OIR strategy. Nevertheless, this further research would be conducted to investigate decremental cost-effectiveness (saving costs due to reduced survival), the ethical implications of which should be considered (see Table 3 3 , 8 , 20 , 22 , 25 , 37 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ).…”

“…50 Nevertheless, there are countries that continue to recommend its prescription 51 , 52 based on early studies that later received heavy criticism. 53 The WHO announced in June 2020 that the hydroxychloroquine arm of the SOLIDARITY trial was stopped, based on findings from the RECOVERY and SOLIDARITY trials. At least 27 trials investigating hydroxychloroquine have been prematurely terminated and 12 withdrawn before enrollment, 3 and some countries have banned the drug in the treatment of COVID-19.…”

“…A summary of policy implications for each of the included treatments is provided in Table 3 . 3 , 8 , 20 , 22 , 23 , 24 , 25 , 37 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 …”

Emerging Therapies for COVID-19: the value of information from more clinical trials

“…52 Nevertheless there are countries which continue to recommend its prescription 53,54 based on early studies that later received heavy criticism. 55 The WHO announced in June 2020 that the Hydroxychloroquine arm of the SOLIDARITY trial was stopped, based on findings from the RECOVERY and SOLIDARITY trials. At least 27 trials investigating Hydroxychloroquine have been prematurely terminated and 12 withdrawn prior to enrolment 3 , and some countries have banned the drug in the treatment of COVID-19 56 .…”