Clearing the Fog: Is Hydroxychloroquine Effective in Reducing Coronavirus Disease-2019 Progression? A Randomized Controlled Trial

Abstract

BackgroundHydroxychloroquine (HCQ) has been considered for the treatment of coronavirus disease 2019 , but data on its efficacy are conflicting. We analyzed the efficacy of HCQ along with standard of care (SOC) treatment, compared with SOC alone, in reducing disease progression in mild COVID-19. MethodsA single-center open-label randomized controlled trial was conducted from April 10 to May 31, 2020 at Pak Emirates Military Hospital, Rawalpindi. Five hundred patients of both genders between the ages of 18 and 80 years with mild COVID-19 were enrolled in the study. A total of 349 patients were assigned to the intervention group (standard dose of HCQ plus SOC) and 151 patients were assigned to SOC only. The primary outcome was progression of disease while secondary outcome was polymerase chain reaction (PCR) negativity on days 7 and 14. The results were analyzed on Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY) version 23. A p-value <0.05 was considered significant. ResultsThe median age of the intervention group was 34 ± 11.778 years and control group was 34 ± 9.813 years. Disease progressed in 16 patients, 11 (3.15%) of which were in the intervention group and 5 (3.3%) in the control group (p-value = 0.940). PCR negative cases in intervention and control groups on day 7 were 182 (52.1%) and 54 (35.8%), respectively (p-value = 0.001); and on day 14 were 244 (69.9%) and 110 (72.9%), respectively (p-value = 0.508). Consecutive PCR negativity on days 7 and 14 was observed in 240 (68.8%) patients in the intervention group compared to 106 (70.2%) in the control group (p-value = 0.321). ConclusionThe addition of HCQ to SOC in hospitalized mild COVID-19 patients neither stops disease progression nor helps in early and sustained viral clearance.

Clinical Management of Adult Patients with COVID-19 Outside Intensive Care Units: Guidelines from the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP)

“…The RCTs discussed above also did not show a favorable effect of HCQ in terms of secondary endpoints of major clinical interest such as mortality or progression to mechanical ventilation (see Supplementary Material for more details). Almost all subsequent RCTs (and all the large ones) were in line with these findings, suggesting no substantial effect of HCQ administration in hospitalized patients with COVID-19 [157][158][159][160][161][162][163]. Of note, the results of at least two meta-analyses supported the lack of effect of HCQ in reducing short-term mortality in patients hospitalized with COVID-19, although mostly based on observational studies [164,165].…”

Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19

“…However, only a minimal effect of Zn on the survival of Zn treated (100 mg elemental Zn per day) v. untreated COVID-19 patients was found by others (263) . Supplementation studies using Zn together with the ionophore chloroquine have so far produced contradictory results (264)(265)(266)(267)(268) .…”

Hydroxychloroquine in the treatment of coronavirus disease 2019: Rapid updated systematic review and meta‐analysis

“…Systematic search of PubMed/LitCOVID identified 1517 records with an additional 344 records being retrieved through supplementary search of other sources. After removing duplicates (159 records) and excluding irrelevant/inappropriate records ( n = 1596) through rigorous screening all titles/abstracts, a total of 106 full‐text articles (including pre‐prints) were assessed for eligibility, of which 19 RCTs 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 were finally included and pooled in this systematic review and meta‐analysis.…”

“…Strength of recommendation : All 19 included RCTs 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 were of moderate to good quality with low risk of bias for most domains for the relevant outcomes of interest. However, there was high risk of performance and detection bias due to open‐label nature of most studies without any placebo‐controls and lack of blinding of patients and/or physicians.…”

“…Subgroup analysis: Subgroup analysis for all-cause mortality by severity of disease, dose of HCQ, trial setting, sample size and study design could not identify any significant difference in the overall results, inferences and conclusions of the meta-analysis (data not shown). [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] were of moderate to good quality with low risk of bias for most domains for the relevant outcomes of interest. However, there was high risk of performance and detection bias due to open-label nature of most studies without any placebo-controls and lack of blinding of patients and/or physicians.…”