Running List of Studies Showing Hydroxychloroquine Is Effective Against COVID-19

This is a running list of studies showing that hydroxychloroquine is effective in treating COVID-19.

1. International Journal of Antimicrobial Agents [December 2020]

TITLE: COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study

METHODS: “This retrospective case series study analysed data from COVID-19 outpatients with confirmed SARS-CoV-2 infection treated in a community in New York State, USA, between 18 March 2020 and 14 May 2020. The outcome of patients treated with a specific triple therapy was compared with public reference data of patients in the same community who were not treated with this therapy.”

Sequentially consecutive COVID-19 outpatients aged >18 years at diagnosis were included in the analysis as the treatment group. All patients were White.

CONCLUSION: “In the treatment group, 4 (2.8%) of 141 patients were hospitalised, which was significantly fewer than the 58 (15.4%) of 377 patients in the untreated group. Therefore, the odds of hospitalisation of treated patients was 84% less than in the untreated patients. All hospitalised patients were male, with one in his twenties, two in their forties and one in his seventies. Three (75%) of the four hospitalised patients belonged to risk stratification group B and one (25%) to group A. All patients (100%) reported SOB at the time of consultation. The median time from onset of symptoms to consultation was 4 days. In the treatment group, one patient had to stay only 1 day in hospital, two other patients were discharged as cured and one patient died (see below). No patient was on a ventilator.

This first retrospective case series study of COVID-19 outpatients in a primary care setting showed that risk-stratified treatment early after onset of clinical symptoms with triple therapy of zinc, low-dose HCQ and azithromycin was associated with significantly fewer hospitalisations (OR = 0.16; P < 0.001) in comparison with untreated patients (public reference data) of the same community. 


2. International Journal of Infectious Diseases [July 2020]

TITLE: Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19

METHODS: “This is a comparative retrospective cohort study evaluating clinical outcomes of all consecutive patients hospitalized at the Henry Ford Health System (HFHS) in Southeast Michigan being treated for COVID-19. The organization is a large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Approval for this study was granted by the Henry Ford Hospital IRB (#13897).

CONCLUSION: The results of this study demonstrate that in a strictly monitored protocol-driven in-hospital setting, treatment with hydroxychloroquine alone and hydroxychloroquine + azithromycin was associated with a significant reduction in mortality among patients hospitalized with COVID-19. In this study, among one of the largest COVID-19 hospital patient cohorts (n = 2,541) assembled in a single institution, overall in-hospital COVID-19 associated mortality was 18.1% reflecting a high prevalence of co-morbid conditions in COVID-19 patients admitted to our institution. The independent predictors of mortality in our study included age ≥65 years, CKD, and severe illness at initial presentation as measured by the oxygen saturation levels on admission, and ventilator use reflect findings similar to those reported in earlier studies. These predictors also underscore the high-risk for COVID-19 experienced by residents in our hospital catchment population in Metropolitan Detroit, Michigan. Michigan is among the states with the highest number of cases of COVID-19 and deaths. In Detroit, our residents suffer from substantial preexisting social and racial health disparities that place our patients at increased risk of severe disease and higher mortality.


3.  International Journal of Antimicrobial Agents [August 2020]

TITLE: Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants

METHODS:  “Sciensano, the Belgian Scientific Institute of Public Health, initiated a national surveillance of COVID-19 hospitalised patients that included treatments and outcomes among its variables, enabling the clinical surveillance of drug use and outcome.

“Sciensano’s data collection of patients hospitalised with confirmed COVID-19 was initiated on 14 March 2020, 2 weeks after the first symptomatic case was reported in Belgium, and systematic registering was strongly encouraged by health authorities. Two independent online secured questionnaires in LimeSurvey (LimeSurvey GmbH, Hamburg, Germany) were made available: one with information after admission and the second after discharge. Information collected at admission included sociodemographic characteristics, clinical presentation, co-morbidities, chronic treatment with renin–angiotensin–aldosterone system inhibitors and diagnostic workup. Data collected at discharge included COVID-19 treatment details (antiviral and immunomodulatory drugs, including date of initiation and termination, mode of administration), clinical and laboratory markers of disease severity during hospital stay, admission to the intensive care unit (ICU) and final outcome at hospital discharge (dead or discharged alive).

As recorded on 24 May 2020, the Sciensano database contained a total of 15 544 case records of COVID-19 patients, originating from 109 Belgian hospitals. Among those, both admission and discharge report forms were received for 10,920 patients (21.3%) discharge forms were missing for patients with admission data and 1313 (8.4%) admission forms were missing for patients with discharge data. After having excluding patients not meeting the inclusion criteria, 8910 cases were included for the descriptive analysis.

CONCLUSION: In this large analysis of patients admitted for COVID-19 in Belgium, HCQ monotherapy administered at a dosage of 2400 mg over 5 days was independently associated with a lower in-hospital mortality rate compared with patients treated with supportive care only, even after adjustment for age, major co-morbidities and disease severity at admission. Importantly, mortality was reduced regardless of the time from symptom onset to diagnosis and HCQ treatment initiation.


4. New Microbes and New Infections [November 2020]

TITLE: Hydroxychloroquine is effective, and consistently so when provided early, for COVID-19: a systematic review

METHODS: “Hydroxychloroquine (HCQ) has shown efficacy against coronavirus disease 2019 (COVID-19) in some but not all studies. We hypothesized that a systematic review would show HCQ to be effective against COVID-19, more effective when provided earlier, not associated with worsening disease and safe. We searched PubMed, Cochrane, Embase, Google Scholar and Google for all reports on HCQ as a treatment for COVID-19 patients. This included preprints and preliminary reports on larger COVID-19 studies. We examined the studies for efficacy, time of administration and safety. HCQ was found to be consistently effective against COVID-19 when provided early in the outpatient setting. It was also found to be overall effective in inpatient studies. No unbiased study found worse outcomes with HCQ use. No mortality or serious safety adverse events were found. HCQ is consistently effective against COVID-19 when provided early in the outpatient setting, it is overall effective against COVID-19, it has not produced worsening of disease and it is safe.”

CONCLUSION: “This review found four important results. The first is that HCQ appears to be consistently effective for the treatment of COVID-19 when provided early in the course of disease in the outpatient setting, and it is generally more effective the earlier it is provided. The second is that overall, in most studies, HCQ exhibits efficacy against COVID-19. The third is that there are no unbiased studies showing a negative effect of HCQ treatment of COVID-19. The fourth is that HCQ appears to be safe for the treatment of COVID-19 when used responsibly.


5. International Journal of Research in Medical Sciences [November 2020]

TITLE: Pre-exposure hydroxychloroquine prophylaxis for COVID-19 in healthcare workers: a retrospective cohort

METHODS: “This retrospective cohort study explores the potential of hydroxychloroquine (HCQ) as a pre- exposure prophylaxis for COVID-19 among 106 health care workers (HCW) exposed to COVID-19 patients, at a tertiary care hospital in India where there was an abrupt cluster outbreak within on duty personnel. HCWs who had voluntarily taken HCQ prior to exposure were considered one cohort while those who had not were considered to be the Control group. All participants with a verifiable high-risk contact history were tested for COVID-19 by RT- PCR.”


“The two cohorts were comparable in terms of age, gender, co-morbidity and exposure. The primary outcome was incidence rates of RT-PCR positive COVID-19 infection among HCQ users and Controls. 106 HCW [healthcare workers] were examined of whom 54 were HCQ users. The comparative analysis of incidence of infection between the two groups demonstrated that voluntary HCQ usage was associated with lesser likelihood of developing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (4 out of 54 HCW), compared to those who were not on it (20 out of 52 HCW), χ2=14.59, p<0.001. None of the HCQ users noted any serious adverse effects.

The study demonstrated that voluntary pre- exposure HCQ prophylaxis by HCWs is associated with a statistically significant reduction in risk of SARS-CoV-2.” 


6. BMC Infectious Diseases [January 2021]

TITLE: Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study


“We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching.”


“Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available.”

In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.


7. Journal of Infection and Public Health [December 2020]

TITLE: Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir

METHODS: “Single center retrospective designed observational study conducted in Ankara City Hospital. Patients who were hospitalized between March 15, 2020 and June 1, 2020 in COVID-19 inpatient clinics with laboratory confirmed diagnosis of COVID-19 were included in the study. An inverse probability of treatment weighting (IPTW) for multiple treatment groups approach was used to balance the differences in several variables on admission.”

CONCLUSION: “Among 2441 patients hospitalized with diagnosis of COVID-19 during the study period, 824 were eligible for the analysis. Median age of patients was 42 (18-93 years). Among all, 347 (43.2%) of the patients had mild disease, 470 (56.8%) had pneumonia. Propensity scores ranged from 0.1841 to 0.9381 in the HCQ group, from 0.03643 to 0.29885 in the favipiravir group, and from 0.03542 to 0.56184 in the HCQ plus favipiravir group. After IPTW for multiple treatment groups was applied, all the covariates in the planned propensity score had weighted standardized effect sizes below 10% which were ranged from 0.005 to 0.092. Multivariate analysis of treatment effect (adjusted effect of treatment) was indicated that there is no statistically significant difference between HCQ, favipiravir, and HCQ plus favipiravir treatment. After using combination of SMOTE and Bootstrap resampling approach, we found no statistically significant difference between HCQ and HCQ plus favipiravir groups in terms of ICU admission. However, compared with the HCQ group, ICU admission rate was statistically significantly higher in the favipiravir group. We obtained the similar results after the sensitivity analysis.”

HCQ with or without favipiravir treatment is associated with reduced risk of ICU admission compared to favipiravir alone in mild to moderate COVID-19 adult patients.


8. Journal of Marine Medical Society [November 2020]

TITLE: Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience

METHODS: “All HCWs included in the study were divided into two groups based on their exposure of COVID-19. The HCWs working directly in contact with confirmed cases of COVID-19 (at hospital designated facilities such as COVID-19 ward, COVID intensive care unit [ICU], and acute respiratory outpatient department), laboratory technicians working in COVID-19 laboratory and radiological technicians handling COVID-19 cases, support staff like helpers, and hygiene staff working in COVID-19 facilities, were considered a high exposure group (HEG). HCWs not included in the HEG group, but working in the mixed COVID-19 facility, were considered in the low exposure group.

The basic demographic profile of all participants was recorded including their underlying comorbidities and type of exposure. The data were collected using an online questionnaire form. The details of HCQ usage including dosage schedule, compliance, and side effects were recorded. HCWs were divided into two groups – those taking adequate dosage and compliant with HCQs and those not compliant with adequate HCQ (which included those not taking HCQ, poor compliance, or early stopping of HCQ).

HCWs with fever, cough, dyspnea, or any symptom suggestive of COVID-19; HCWs with history of unprotected exposure to COVID-19 cases; and HCWs working in COVID-19 ward/ICU after completing their duty and quarantine period, were tested for COVID-19, as per hospital policy. Swabs from nasopharynx and oropharynx were taken and tested by reverse transcription–polymerase chain reaction which used the TaqMan fluorogenic probe-based chemistry that uses the 5′-nuclease activity of Taq DNA polymerase.

All COVID-19-confirmed HCWs were hospitalized and managed as per hospital protocol. The details of clinical profile and course of illness were collected from the patient records.”

CONCLUSION: “The use of HCQ as preexposure prophylaxis in HCWs was associated with reduced risk of COVID-19, suggesting its role as an effective chemoprophylactic agent. Therefore, in the absence of robust data in the present pandemic scenario, we recommend continued use of HCQ prophylaxis for COVID-19 in HCWs, based on the ICMR guidelines.


9. BioScience Trends

TITLE: Efficacy of early hydroxychloroquine treatment in preventing
COVID-19 pneumonia aggravation, the experience from Shanghai,

METHODS: “The aim of this study is to assess the efficacy of multiple treatments, especially hydroxychloroquine, used in different disease stages of coronavirus disease 2019 (COVID-19). All consecutive patients with COVID-19 admitted to Shanghai Public Health Clinical Center (Shanghai, China) between January 20, 2020, and April 30, 2020, were enrolled, and their clinical data were retrospectively collected. Binary logistic regression was used to screen the factors associated with disease aggravation, and multivariable analyses with the Cox proportional hazards model were used to estimate the effects of prognostic factors on the improvement time and PCR conversion days in throat swabs and stool swabs. A total of 616 patients, including 50 (8.11%) severe and 18 (2.92%) critical patients, were enrolled in our retrospective cohort study. The early use of hydroxychloroquine was a protective factor associated with disease aggravation (95% CI: 0.040-0.575, p = 0.006). Clinical improvement by 20 days was significantly different between patients with hydroxychloroquine used early and those with hydroxychloroquine not used (p = 0.016, 95% CI: 1.052-1.647). The median time to clinical improvement was 6 days in the hydroxychloroquine used early group, compared with 9 days in the without hydroxychloroquine used group and 8 days in the with hydroxychloroquine not used early group (p < 0.001). Hydroxychloroquine used early was associated with earlier PCR conversion in both throat swabs (HR = 1.558, p = 0.001) and stool swabs (HR = 1.400, p = 0.028). The use of hydroxychloroquine at an early stage is a potential therapeutic strategy for treating patients before irreversible severe respiratory complications occur. The early use of hydroxychloroquine decreased the improvement time and the duration of COVID-19 detection in throat and stool swabs.”

CONCLUSION: “Research has reported that the administration of
hydroxychloroquine did not result in a significantly higher probability of negative conversion than the standard of care alone in patients with COVID-19 (17). However, in our research, the administratio of hydroxychloroquine was specified. The early use of hydroxychloroquine, which is the use of
hydroxychloroquine within 5 days of diagnosis, was found to decrease the swab PCR conversion days. Furthermore, the early use of hydroxychloroquine was also found to prevent the progression of the disease aggravation from mild and moderate to severe and
critical. The use of hydroxychloroquine at an early stage is a potentially life-saving therapeutic strategy both to treat and cure patients before irreversible severe respiratory complications occur.
Though hydroxychloroquine was found to prevent disease aggravation in our study, it was not significantly associated with a decrease in in-hospital mortality (18). Therefore, in the late stage of COVID-19 disease, hydroxychloroquine was not recommended as a lifesaving treatment.”


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