COVID-19 Treatment Analysis

@CovidAnalysis

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Treatment effectiveness	Potential lives saved
1%
10%
25%
50%

PrEP
100%

PEP
100%

Early
100%

Late
61%

All
75%

68 studies (41 peer reviewed)
COVID deaths:

Global HC Q studies. PrEP, PEP, and early treatment studies show high effectiveness, while late treatment shows mixed results.


8/4	Positive (news) POSITIVE	Late	Iacoviello et al., upcoming study (News) (not included in the study count)	INTERVIEW EXCLUSIVE : Efficacité de l'hydroxych loroquine confirmée sur 3451 patients italiens. Réduction de la mortalité de 30%
		Upcoming study of 3,451 hospitalized patients in Italy reports that HC Q results in a 30% reduction in mortality. Treatment started on the first day of admission in most cases.
8/4	Positive (news) POSITIVE	Late treatment study Source Study Page Late treatment study
		Iacoviello et al., upcoming study (News) (not included in the study count)
		INTERVIEW EXCLUSIVE : Efficacité de l'hydroxych loroquine confirmée sur 3451 patients italiens. Réduction de la mortalité de 30%
		Upcoming study of 3,451 hospitalized patients in Italy reports that HC Q results in a 30% reduction in mortality. Treatment started on the first day of admission in most cases. Currently no formal study is available so this is not included in the study count.
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8/4	Inconc. INCONC.	Late	Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint)	Clearing the fog: Is HC Q effective in reducing COVID-19 progression: A randomized controlled trial
		Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HC
8/4	Inconc. INCONC.	Late treatment study Source Study Page Late treatment study
		Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint)
		Clearing the fog: Is HC Q effective in reducing COVID-19 progression: A randomized controlled trial
		Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HC Q treatment, 52.1% (HC Q) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases). Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured. As with other studies, PCR may detect non-replicable viral nucleic acid, this is more likely at day 14. Details on the test accuracy are not provided, authors note that RT-PCR sensitivity ranges from 34-80%.
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8/2	Positive POSITIVE	Late	Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed)	Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
		Retrospective of 132 hospitalized patients. HC Q+AZ significantly reduces death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay..
8/2	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed)
		Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
		Retrospective of 132 hospitalized patients. HC Q+AZ significantly reduces death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admission to treatment 0.7 days.
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8/2	In Vitro IN VITRO	In Vitro	Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count)	A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Ch loroquine Activity
		In vitro study presenting a new theory on SARS-CoV-2 infection and why HC Q/C Q provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and..
8/2	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count)
		A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Ch loroquine Activity
		In vitro study presenting a new theory on SARS-CoV-2 infection and why HC Q/C Q provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms the importance of accurate dosing. Metabolic analysis revealed HC Q/C Q inhibit oxidative phosphorylation in mitochondria (likely by sequestering protons needed to drive ATP synthase), inhibiting infection and/or slowing replication.
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7/29	Positive POSITIVE	Late	D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter)	Effectiveness of Hydroxych loroquine in COVID-19 disease: A done and dusted situation?
		HC Q+AZ adjusted death HR 0.44, p=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline ..
7/29	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter)
		Effectiveness of Hydroxych loroquine in COVID-19 disease: A done and dusted situation?
		HC Q+AZ adjusted death HR 0.44, p=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline plasma CRP. IPW censoring. Retrospective study of 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission. HC Q 197 patients, HC Q+AZ 94, control 92. Control group received various other treatments. Authors excluded people receiving other drugs which could have biased the effect of HC Q when used in combination. Residual confounding is possible (e.g., people with CVD were more frequent in control), however people in the control group were more likely to require mechanical ventilation.
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7/26	Inconc. INCONC.	PEP	Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint)	A Cluster-Randomized Trial of Hydroxych loroquine as Prevention of Covid-19 Transmission and Disease
		Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - ..
7/26	Inconc. INCONC.	Post Exposure Prophylaxis study Source Study Page Post Exposure Prophylaxis study
		Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint)
		A Cluster-Randomized Trial of Hydroxych loroquine as Prevention of Covid-19 Transmission and Disease
		Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - 1.17], vs. overall 0.89, possibly because the exposure events are identified faster in this context, versus home exposure where testing of the source may be more delayed. The trial is too small for significance here. If the trend continued this result would be significant at p<0.05 after about 25% more patients were added. Enrollment was up to 7 days after exposure, median 4 days. Treatment delay is unclear. The exposure event timing is not detailed. It appears to be based on the date of a positive test for a contact, which is likely to be much later than the actual exposure time. 13.1% were already positive at baseline, which is consistent with the actual exposure time being significantly earlier. PCR testing has a very high false-negative rate in early stages (e.g., 100% on day 1, 67% on day 4, and 20% on day 8 [1]), hence it is likely that a much higher percentage were infected at an unknown time before enrollment. Medication administration is not detailed. Sensitivity and specificity of the tests is not provided. Given the delay identifying index cases, PCR test delay, and PCR false negative rate at early stages, the treatment delay in general was very long and could be over 2 weeks. The RR for non-PCR positive at baseline is 0.74. Including the PCR-positive at baseline patients reduced this to 0.89. This is also consistent with earlier treatment being more effective. The paper does not mention zinc. Zinc deficiency in Spain has been reported at 83% [2], this may significantly reduce effectiveness. HC Q is a zinc ionophore which increases cellular uptake, facilitating significant intracellular concentrations of zinc, and zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 [3]. This study focuses on the existence of symptoms or PCR-positive results, however severity of symptoms is more important. Research has shown HC Q concentrations can be much higher in the lung compared to plasma [4], which may help minimize the occurrence of severe cases and death. There is a treatment-delay response relationship consistent with an effective treatment, however the authors only provide 3 ranges and do not break down the earliest treatment delay times. The definition of COVID-19 symptoms is very broad - just existence of a headache alone or muscle pain alone was considered COVID-19. There was an overall very low incidence of confirmed COVID-19 (138 cases across both arms). There were no serious adverse events that were adjudicated as being treatment related. Authors exclude those with symptoms in the previous two weeks, however, those with symptoms up to several months before may still test PCR-positive even though there may be no viable virus. There appears to be incorrect data. Table 2, secondary outcomes, control, hospital/vital records shows that 8 of 1042 is 9.7% (we get 0.8%). Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding [5]. In summary, this study appears positive in the context of very delayed treatment and very small sample sizes, however we have classified it as inconclusive for now pending further analysis and feedback. Preliminary analysis. Supplementary Appendix is not currently available. Please submit any corrections or comments. [1] acpjournals.org/doi/10.7326/M20-1495 [2] mdpi.com/2072-6643/9/7/697 [3] infezmed.it/index.php/article?Anno=2020&numero=2&ArticoloDaVisualizzare=Vol_28_2_2020_192 [4] ncbi.nlm.nih.gov/pmc/articles/PMC7122276/ [5] journal.chestnet.org/article/S0012-3692(20)31718-9/fulltext
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7/24	Positive POSITIVE	PrEP	Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint)	Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital
		Study of hospital health care workers showing HC Q prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis wa..
7/24	Positive POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint)
		Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital
		Study of hospital health care workers showing HC Q prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HC Q (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HC Q may be larger because severity of symptoms are not considered here but HC Q may also reduce severity.
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7/23	Negative NEGATIVE	Late	Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed)	Hydroxych loroquine with or without Azithromycin in Mild-to-Moderate Covid-19
		Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot de..
7/23	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed)
		Hydroxych loroquine with or without Azithromycin in Mild-to-Moderate Covid-19
		Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HC Q) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of the medications >24hrs. Analyzing these patients rather than excluding them may have revealed effectiveness with early use as shown in other studies. The trial initially required enrollment within 48 hours of admission and was changed to remove this requirement, this change is likely to reduce effectiveness because enrollment was moved later, compared to the time the disease became serious enough for hospitalization.
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7/22	In Vitro IN VITRO	In Vitro	Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count)	Ch loroquine does not inhibit infection of human lung cells with SARS-CoV-2
		The title of this paper does not appear to match the results. Fig. 1b @100uM shows C Q results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementa..
7/22	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count)
		Ch loroquine does not inhibit infection of human lung cells with SARS-CoV-2
		The title of this paper does not appear to match the results. Fig. 1b @100uM shows C Q results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementary data at this time so this is estimated from the graph). This decrease may continue if examined over longer time periods. Fig. 1a shows a ~45-50% entry inhibition @100uM for HC Q/C Q (p=0.0005/0.0045), ~10-30% @10uM (p=0.13/0.99). Inhibition is significantly better with Vero cells. In vitro study of C Q and HC Q inhibition of SARS-CoV-2 into Vero (kidney), Vero-TMPRSS2, and Calu-3 (derived from human lung carcinoma) cells. Although there are several theories on how HC Q may help with COVID-19, authors do not consider the most common theory where HC Q functions as a zinc ionophore, facilitating significant intracellular concentrations of zinc. Zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 [1]. Calu-3 is one of many cell lines derived from human lung carcinomas [2]. Calu-3 cells resemble serous gland cells. They do not express 15-lipoxygenase, an enzyme specifically localized to the surface epithelium, but they do express secretory component, secretory leukocyte protease inhibitor, lysozyme, and lactoferrin, all markers of serous gland cells. [3] note that the absence of systemic inflammation, circulatory factors, and other paracrine systemic influences is a potential limitation of the isolated cell system. RT-PCR is used, we note that nucleic acid may persist even after the virus is no longer viable [4]. It is unclear how the authors conclude "C Q does not block SARS-CoV-2 infection of Calu-3" cells, when the results show statistically significant inhibition at higher concentrations. Further, it is unclear how the authors go from these results in one specific type of pulmonary adenocarcinoma cells that resemble serous gland cells, in vitro, into the title of the paper which claims no inhibition in lung cells. Further, it is unclear how another leap is made to "will not be effective against COVID-19" given the multiple theories of HC Q/C Q effectiveness. [1] infezmed.it/index.php/article?Anno=2020&numero=2&ArticoloDaVisualizzare=Vol_28_2_2020_192 [2] journals.physiology.org/doi/pdf/10.1152/ajplung.1994.266.5.L493 [3] journals.physiology.org/doi/pdf/10.1152/ajplung.1994.266.5.L493 [4] fda.gov/media/136472/download
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7/21	Positive POSITIVE	Late	Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint)	Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
		HC Q HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative ..
7/21	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint)
		Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
		HC Q HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative effect.
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7/20	Meta (positive) META	Early	Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included in the study count)	Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”
		Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit.
7/20	Meta (positive) META	Early treatment study Source Study Page Early treatment study
		Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included in the study count)
		Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”
		Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit. Meta studies are not included in the percentages or study count.
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7/18	Meta (positive) META	PEP	Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in the study count)	Efficacy of Hydroxych loroquine as Prophylaxis for Covid-19
		Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HC Q is effective when used early, p<0.01. The effectiveness found is especially notable considering the limitatio..
7/18	Meta (positive) META	Post Exposure Prophylaxis study Source Study Page Post Exposure Prophylaxis study
		Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in the study count)
		Efficacy of Hydroxych loroquine as Prophylaxis for Covid-19
		Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HC Q is effective when used early, p<0.01. The effectiveness found is especially notable considering the limitations of the study. Treatment was relatively late, with enrollment up to 4 days after exposure, and an unspecified shipping delay. While the paper does not provide shipping details, the study protocol gives some detail allowing us to estimate the treatment delay as ~70 to 140 hours after exposure on average for the 1-4 days since enrollment specified in the paper (we will update this when authors respond to our request for details). There was only 75% medication adherence, including 16% who did not take the medication at all. The study relies on Internet surveys. Meta studies are not included in the percentages or study count.
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7/16	Positive POSITIVE	Early	Hong et al., Infect. Chemother., 2020, 52:e43 (Peer Reviewed)	Early Hydroxych loroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
		HC Q 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report..
7/16	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Hong et al., Infect. Chemother., 2020, 52:e43 (Peer Reviewed)
		Early Hydroxych loroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
		HC Q 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HC Q significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HC Q as soon as possible. 42 patients with HC Q 1-4 days from diagnosis, 48 with HC Q 5+ days from diagnosis.
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7/16	Inconc. INCONC.	Early	Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed)	Hydroxych loroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
		~70 to 140 hour (inc. shipping) delayed outpatient treatment with HC Q reduced combined hospitalization/death by 50%, p=0.29 (5 HC Q cases, 10 control cases), and reduced hospitalization by 60%,..
7/16	Inconc. INCONC.	Early treatment study Source Study Page Early treatment study
		Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed)
		Hydroxych loroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
		~70 to 140 hour (inc. shipping) delayed outpatient treatment with HC Q reduced combined hospitalization/death by 50%, p=0.29 (5 HC Q cases, 10 control cases), and reduced hospitalization by 60%, p=0.17. There was one hospitalized control death and one non-hospitalized HC Q death. It is unclear why there was a non-hospitalized death, external factors such as lack of standard care may be involved. Excluding that case results in one control death and zero HC Q deaths (not statistically significant but noted as reducing mortality is the most important outcome). Details for the hospitalizations and deaths such as medication adherence and treatment delay may be informative but are not provided. The paper states the end point was changed from hospitalization/death to symptom severity because they would have required 6,000 participants. However, if the observed trend continued, they would hit 95% significance on the reduction in hospitalization at ~725 patients, and 95% on the reduction in combined hospitalization/death at ~1,145 patients, which is a lot less than 6,000, and also less than the original plan of 1,242 patients. We hope the trial can be continued for statistical significance. Treatment is relatively late, ~70 to 140 hours after symptoms, including the shipping delay. The paper does not mention the shipping delay but partial details are provided in the study protocol. They are not clear but indicate no shipping on the weekends and a possible 12pm cutoff for same day dispensing and mailing. Assuming that enrollments were evenly distributed between 6am and 12am each day, we get an average of ~46 hours shipping delay. We have asked for shipping details and will update with more accurate values when available. In any case the treatment delay is quite long and there is no overlap with the more typical delays used such as 0 - 36 hours for oseltamivir. The paper compares 0 - 36 hour delayed treatment with oseltamivir (influenza) and ~70 to 140 hour delayed treatment with HC Q (COVID-19), noting that oseltamivir seemed more effective. However, a more comparable study is McLean (2015) who showed that 48 - 119 hour delayed treatment with oseltamivir has no effect. This suggests that HC Q is more effective than oseltamivir, and that HC Q may still have significant effect for some amount of delay beyond the delay where oseltamivir is effective. 6 people were included that enrolled with >4d symptoms, although they do not match the study inclusion criteria. This reduces observed effectiveness. The paper says 56% (236) were enrolled within 1 day of symptoms, but results show only 40% for "<1d", 56% is possibly for <48hrs, we have asked for clarification. Patients in this study are relatively young and most of them recover without assistance. This reduces the room for a treatment to make improvements. The maximum improvement of an effective treatment would be expected before all patients approach recovery, as shown in the figure below. Authors focus on the end result where most have recovered, but it is more informative to examine the curve and the point of maximum effectiveness. Authors did not collect data for every day but they do have interim results for days 3, 5, 10. The results are consistent with an effective treatment and show a statistically significant improvement, p = 0.05, at day 10 (other unreported days might show increased effectiveness). Results also show a larger treatment effect for those >50, not statistically significant due to the small sample, but noted as COVID-19 risk dramatically increases with age. The effect may be more visible here because younger patients may on average have more mild cases with less room for improvement. In general patients in this study have relatively mild symptoms on average, limiting the chance to observe improvement. The study relies on Internet surveys. Known fake surveys were submitted to the similar PEP trial and there could be an unknown number of undetected fake surveys in both trials. The study shows a high incidence of side effects in the placebo arm, which could be in part due to fake entries [1]. The granularity change in the histograms of Figure S4 raise concerns [2]. Data on increasing severity, less affected by the lower bound where everyone has recovered, also supports effectiveness [3]. Research shows the placebo used in the US may be protective for COVID-19 [4] so the true effectiveness of HC Q could be higher than observed. Treatment delay reporting has changed from the companion PEP trial which reported results for enrollment delays 1, 2, 3, and 4 separately (and from which we can confirm a statistically significant delay-response relationship), while this trial combines 1-2 and 3-4, and adds <1. Since the two trials share reporting (some patients were moved between trials) it's not clear how the new category was added. RCT of 423 patients with Internet surveys. Medication adherence was only 77% so the true effect of treatment is likely higher. Analysis of primarily low risk patients, authors note the results are not generalizable to the COVID high-risk population. We will update when hearing back on questions asked. In summary, we believe the results of this study are positive for HC Q being an effective treatment, however we have classified this study as inconclusive for now pending feedback and further analysis. [1] twitter.com/Covid19Crusher/status/1284515906375356416 [2] twitter.com/Covid19Crusher/status/1284515906375356416 [3] twitter.com/Covid19Crusher/status/1284515906375356416 [4] frontiersin.org/articles/10.3389/fphar.2020.01062/full
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7/16	Inconc. INCONC.	Early	Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed)	Hydroxych loroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
		This paper has inconsistent data - some of the values reported in Table 2 and the abstract correspond to 12 control hospitalizations, while others correspond to 11 control hospitalizations. There was a 25% reduction in hospitalization an..
7/16	Inconc. INCONC.	Early treatment study Source Study Page Early treatment study
		Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed)
		Hydroxych loroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
		This paper has inconsistent data - some of the values reported in Table 2 and the abstract correspond to 12 control hospitalizations, while others correspond to 11 control hospitalizations. There was a 25% reduction in hospitalization and 16% reduction in the median time to symptom resolution for HC Q, without statistical significance due to small samples. Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. We have asked for details of the treatment delay and will update when hearing back. They do not break down results by treatment delay. The paper does not mention zinc. Zinc deficiency in Spain has been reported at 83% [1], this may significantly reduce effectiveness. HC Q is a zinc ionophore which increases cellular uptake, facilitating significant intracellular concentrations of zinc, and zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 [2]. Undetectable viral load was changed to 3 log10 copies/mL potentially masking effectiveness. For viral load authors use nasopharyngeal swabs, we note that viral activity in the lung may be especially important for COVID-19, and that research has shown HC Q concentrations can be much higher in the lung compared to plasma [3]. We also note that viral detection by PCR does not equate to viable virus [4]. Accuracy of the tests is not provided. Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding [5]. 293 low-risk patients with no deaths. No serious adverse events. We have asked for more details on the treatment delay and viral load change and will update when hearing back. [1] mdpi.com/2072-6643/9/7/697 [2] infezmed.it/index.php/article?Anno=2020&numero=2&ArticoloDaVisualizzare=Vol_28_2_2020_192 [3] ncbi.nlm.nih.gov/pmc/articles/PMC7122276/HCQ [4] ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Stateme.. [5] journal.chestnet.org/article/S0012-3692(20)31718-9/fulltext
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7/9	Meta (positive) META	Early, Late	Raoult et al., Preprint (Preprint) (meta analysis - not included in the study count)	Hydroxych loroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier)
		Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients.
7/9	Meta (positive) META	Early, Late Source Study Page Early, Late
		Raoult et al., Preprint (Preprint) (meta analysis - not included in the study count)
		Hydroxych loroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier)
		Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients. Meta studies are not included in the percentages or study count.
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7/7	Negative NEGATIVE	Late	An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint)	Treatment Response to Hydroxych loroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
		Retrospective of hospitalized patients with 31 HC Q patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. ..
7/7	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint)
		Treatment Response to Hydroxych loroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
		Retrospective of hospitalized patients with 31 HC Q patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP". We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender [1]. In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus was not found after the second week of illness despite the persistence of PCR detection of RNA” [2]. [1] ncbi.nlm.nih.gov/pmc/articles/PMC7247289/ [2] ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Stateme..
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7/3	Positive POSITIVE	PrEP	Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed)	COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study
		Rheumatic disease patients on HC Q had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythemat..
7/3	Positive POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed)
		COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study
		Rheumatic disease patients on HC Q had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in other family members, and comorbidities. 43 patients with rheumatic disease and COVID-19 exposure.
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7/3	Positive POSITIVE	Early	Scholz et al., Preprints 2020, 2020070025, doi:10.20944/preprints202007.0025.v1 (Preprint)	COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxych loroquine and Azithromycin: A Retrospective Case Series Study
		Early treatment with HC Q+AZ+Z results in 84% lower hospitalization and 80% lower death - hospitalization OR 0.16 (p<0.001), death OR 0.2 (p=0.16). No cardiac side effects. Retrospective 518 patients (141 treated, 37..
7/3	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Scholz et al., Preprints 2020, 2020070025, doi:10.20944/preprints202007.0025.v1 (Preprint)
		COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxych loroquine and Azithromycin: A Retrospective Case Series Study
		Early treatment with HC Q+AZ+Z results in 84% lower hospitalization and 80% lower death - hospitalization OR 0.16 (p<0.001), death OR 0.2 (p=0.16). No cardiac side effects. Retrospective 518 patients (141 treated, 377 control).
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7/1	Positive POSITIVE	Late	Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed)	Treatment with Hydroxych loroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
		HC Q decreases mortality from 26.4% to 13.5% (HC Q) or 20.1% (HC Q+AZ). Propensity matched HC Q HR 0.487, p=0.009. Michigan 2,541 patients retrospecti..
7/1	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed)
		Treatment with Hydroxych loroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
		HC Q decreases mortality from 26.4% to 13.5% (HC Q) or 20.1% (HC Q+AZ). Propensity matched HC Q HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HC Q group average age is 5 years younger and the percentage of male patients is 4% higher which is likely to favor the treatment and the control respectively in the before-propensity matching results. Some reported limtiations of this study are inaccurate [1]. Corticosteroids were controlled for in the multivariate and propensity analyses as were age and comorbidities including cardiac disease and severity of illness. Age was an independent risk factor associated with mortality. HC Q was independently associated with decreased mortality, distinct from the steroid effect. 91% of all patients began treatment within two days of admission. HC Q was used throughout the study period, limiting time bias. Patients assigned to HC Q group had moderate and severe illness at presentation, which would favor worse outcome with HC Q. [1] ijidonline.com/article/S1201-9712(20)30604-4/fulltext
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7/1	Safety SAFETY	N/A	Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count)	Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc)
		In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients wit..
7/1	Safety SAFETY	N/A Source Study Page N/A
		Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count)
		Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc)
		In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. However, providers still need to be vigilant for comorbidities that may independently place patients at risk for arrhythmias. COVID-19 treatment using HC Q leads to significant QTc prolongation, but was not associated with arrhythmias in pediatric patients. The long term sequelae of arrhythmia development in this population and their impact on outcome needs to be studied.
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6/30	Positive POSITIVE	Late	Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed)	Risk Factors for Mortality in Patients with COVID-19 in New York City
		HC Q decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
6/30	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed)
		Risk Factors for Mortality in Patients with COVID-19 in New York City
		HC Q decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
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6/29	Positive POSITIVE	PrEP	Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed)	Chronic treatment with hydroxych loroquine and SARS-CoV-2 infection
		Chronic treatment with HC Q provides protection against COVID, odds ratio 0.51 (0.37-0.70). Note that patients with SLE, RA, and other autoimmune conditions have a significantly increased susceptibility to and incide..
6/29	Positive POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed)
		Chronic treatment with hydroxych loroquine and SARS-CoV-2 infection
		Chronic treatment with HC Q provides protection against COVID, odds ratio 0.51 (0.37-0.70). Note that patients with SLE, RA, and other autoimmune conditions have a significantly increased susceptibility to and incidence of infections, so the actual benefit may be significantly higher [1, 2, 3, 4, 5, 6, 7]. [1] advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-019-0055-y [2] ncbi.nlm.nih.gov/pmc/articles/PMC6099129/ [3] pubmed.ncbi.nlm.nih.gov/27370880/ [4] pubmed.ncbi.nlm.nih.gov/8778988/ [5] pubmed.ncbi.nlm.nih.gov/23192911/ [6] pubmed.ncbi.nlm.nih.gov/11447699/ [7] pubmed.ncbi.nlm.nih.gov/30954968/
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6/29	Safety SAFETY	N/A	Mfeukeu-Kuate et al. (Preprint) (not included in the study count)	Electrocardiographic safety of daily Hydroxych loroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon
		No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HC Q+AZ. 51 relatively young patients 39 +/- 11.
6/29	Safety SAFETY	N/A Source Study Page N/A
		Mfeukeu-Kuate et al. (Preprint) (not included in the study count)
		Electrocardiographic safety of daily Hydroxych loroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon
		No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HC Q+AZ. 51 relatively young patients 39 +/- 11.
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6/25	Positive POSITIVE	Early	Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed)	Outcomes of 3,737 COVID-19 patients treated with hydroxych loroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
		Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients.
6/25	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed)
		Outcomes of 3,737 COVID-19 patients treated with hydroxych loroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
		Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients.
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6/22	In Vitro IN VITRO	In Vitro	Wang et al., bioRxiv, doi:10.1101/2020.06.22.164665 (Preprint) (In Vitro) (not included in the study count)	Ch loroquine and hydroxych loroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus
		In vitro study, not included in the study count or percentages. C Q and HC Q inhibit the entry of COVID-19 spike pseudotype virus using ACE2 high expressed HEK293T cells.
6/22	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Wang et al., bioRxiv, doi:10.1101/2020.06.22.164665 (Preprint) (In Vitro) (not included in the study count)
		Ch loroquine and hydroxych loroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus
		In vitro study, not included in the study count or percentages. C Q and HC Q inhibit the entry of COVID-19 spike pseudotype virus using ACE2 high expressed HEK293T cells.
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6/22	Positive POSITIVE	Early	Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint)	Efficacy and safety of ch loroquine or hydroxych loroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
		Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HC Q), p=0.01. 67 patients with mild/moderate cases.
6/22	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint)
		Efficacy and safety of ch loroquine or hydroxych loroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
		Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HC Q), p=0.01. 67 patients with mild/moderate cases.
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6/19	Positive (news) POSITIVE	PrEP	SMSH Sawai Man Singh Hospital, India (News) (not included in the study count)	HC Q beneficial as preventive drug: SMS doctors told ICMR
		PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered.
6/19	Positive (news) POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		SMSH Sawai Man Singh Hospital, India (News) (not included in the study count)
		HC Q beneficial as preventive drug: SMS doctors told ICMR
		PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered. Currently no formal study is available so this is not included in the study count.
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6/19	Negative (news) NEGATIVE	Late	NIH, study not available yet (News) (not included in the study count)	NIH halts clinical trial of hydroxych loroquine
		NIH halts late stage trial reporting no harm and no benefit. 470 patients.
6/19	Negative (news) NEGATIVE	Late treatment study Source Study Page Late treatment study
		NIH, study not available yet (News) (not included in the study count)
		NIH halts clinical trial of hydroxych loroquine
		NIH halts late stage trial reporting no harm and no benefit. 470 patients. Currently no formal study is available so this is not included in the study count.
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6/19	Positive POSITIVE	Late	Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint)	Hydroxych loroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France
		Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HC Q and HC Q+AZ. No significant effect is seen on 28-day mortality, however many more control ..
6/19	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint)
		Hydroxych loroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France
		Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HC Q and HC Q+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days suggesting there will be a significant improvement when extending past 28 days. Note that the median age is higher in the group not treated with HC Q or AZ. For other issues with the adjustments see [1]. Also see the analysis here [2]. We received feedback from one person that thinks the trial should be considered negative because the control patients still in hospital should be disregarded. However, based on other studies, it seems very likely that a significant number of deaths in the control group occurred past 28 days whereas no treated patients remained in hospital. This should be simple for the authors to resolve by extending the analysis. Even if we ignore this, it still shows significantly faster discharge for treatment, so we do not see how we can consider it negative. We note that the substantial reduction in hospital time is a very large cost reduction and may lower mortality in general by reducing the chance of exceeding maximum capacity. Additional feedback is welcome. [1] medrxiv.org/content/10.1101/2020.06.16.20132597v1#disqus_thread [2] twitter.com/Covid19Crusher/status/1274668697408471040
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6/18	Inconc. INCONC.	Late	Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed)	Compassionate use of hydroxych loroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
		Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
6/18	Inconc. INCONC.	Late treatment study Source Study Page Late treatment study
		Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed)
		Compassionate use of hydroxych loroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
		Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
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6/17	Positive POSITIVE	Late	Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed)	Hydroxych loroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China
		30 hospitalized patients. Early use of HC Q is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization.
6/17	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed)
		Hydroxych loroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China
		30 hospitalized patients. Early use of HC Q is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization.
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6/17	Negative (news) NEGATIVE	Late	World Health Organization, study not available yet (News) (not included in the study count)	“Solidarity” clinical trial for COVID-19 treatments
		WHO stopped the Solidarity late stage trial of HC Q reporting no benefit. Later news reported "little or no reduction in mortality" [1]. The study has not been released yet and few details are available. Th..
6/17	Negative (news) NEGATIVE	Late treatment study Source Study Page Late treatment study
		World Health Organization, study not available yet (News) (not included in the study count)
		“Solidarity” clinical trial for COVID-19 treatments
		WHO stopped the Solidarity late stage trial of HC Q reporting no benefit. Later news reported "little or no reduction in mortality" [1]. The study has not been released yet and few details are available. This trial used an extremely high dose which may be related to the relatively poor results [2]. Currently no formal study is available so this is not included in the study count. [1] who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-tr.. [2] francesoir.fr/politique-monde/oxford-recovery-et-solidarity-overdosage-two-clinical-trials-acts-co..
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6/16	Positive (news) POSITIVE	PrEP	WHIP COVID-19 (News) (not included in the study count)	Henry Ford Health System still moving forward with hydroxych loroquine study
		Ongoing WHIP COVID-19 HC Q PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HC Q. For more details on the study se..
6/16	Positive (news) POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		WHIP COVID-19 (News) (not included in the study count)
		Henry Ford Health System still moving forward with hydroxych loroquine study
		Ongoing WHIP COVID-19 HC Q PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HC Q. For more details on the study see [1]. Currently no formal study is available so this is not included in the study count. [1] henryford.com/whip-covid-19
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6/12	Theory THEORY	Theory	Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count)	Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxych loroquine-Azithromycin Combination in COVID-19 Therapy
		Theory paper, not included in the study count or percentages. Proposes a new mechanism supporting the synergistic interaction between HC Q+AZ.
6/12	Theory THEORY	Theory Source Study Page Theory
		Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count)
		Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxych loroquine-Azithromycin Combination in COVID-19 Therapy
		Theory paper, not included in the study count or percentages. Proposes a new mechanism supporting the synergistic interaction between HC Q+AZ.
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6/12	Negative NEGATIVE	Late	Giacomelli et al., medRxiv, doi:10.1101/2020.06.05.20123299 (Preprint)	Early administration of lopinavir/ritonavir plus hydroxych loroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study
		Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". Th..
6/12	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Giacomelli et al., medRxiv, doi:10.1101/2020.06.05.20123299 (Preprint)
		Early administration of lopinavir/ritonavir plus hydroxych loroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study
		Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". The "early" treatment group is significantly older. Severe adverse events attributed by authors to concurrent administration of LPV, making it difficult to make conclusions about HC Q.
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6/10	Positive POSITIVE	Early	Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint)	A short therapeutic regimen based on hydroxych loroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.
		80 moderate cases, HC Q+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy.
6/10	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint)
		A short therapeutic regimen based on hydroxych loroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.
		80 moderate cases, HC Q+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy.
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6/9	Positive POSITIVE	Late	Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed)	Beneficial effect of Hydroxych loroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study
		68 very high risk nursing home residents, median age 86, HC Q+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the med..
6/9	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed)
		Beneficial effect of Hydroxych loroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study
		68 very high risk nursing home residents, median age 86, HC Q+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the median death for the same period in 2019/2018.
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6/9	Positive POSITIVE	PrEP	Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint)	Pre exposure Hydroxych loroquine use is associated with reduced COVID19 risk in healthcare workers
		HC Q reduced cases from 38% to 7%. 106 people. No serious adverse effects.
6/9	Positive POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint)
		Pre exposure Hydroxych loroquine use is associated with reduced COVID19 risk in healthcare workers
		HC Q reduced cases from 38% to 7%. 106 people. No serious adverse effects.
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6/6	Meta (positive) META	Early, Late	Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in the study count)	Clinical Efficacy of Ch loroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
		[H]C Q effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
6/6	Meta (positive) META	Early, Late Source Study Page Early, Late
		Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in the study count)
		Clinical Efficacy of Ch loroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
		[H]C Q effective and reduces mortality by a factor 3. Meta analysis of 20 studies. Meta studies are not included in the percentages or study count.
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6/5	Negative NEGATIVE	Late	Horby et al., medRxiv, 7/15/2020, doi:10.1101/2020.07.15.20151852 (press release 6/5) (Preprint)	Effect of Hydroxych loroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
		RECOVERY trial reports no significant benefit seen for very late stage very sick patients. Results may be due to the unusually high dosage used [1, 2]. Patients were extremely sick (average of 9 days post symptoms, 60% requiring oxygen an..
6/5	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Horby et al., medRxiv, 7/15/2020, doi:10.1101/2020.07.15.20151852 (press release 6/5) (Preprint)
		Effect of Hydroxych loroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
		RECOVERY trial reports no significant benefit seen for very late stage very sick patients. Results may be due to the unusually high dosage used [1, 2]. Patients were extremely sick (average of 9 days post symptoms, 60% requiring oxygen and an additional 17% requiring ventilation/ECMO), and unusually high death rate was seen in both arms. 1,561 HC Q patients, 3,155 SOC. A secondary analysis has found several inconsistencies in the data [3], and found evidence of excess mortaliy within the first few days that could be due to overdose. [1] twitter.com/JamesTodaroMD/status/1272661099985481733 [2] twitter.com/JamesTodaroMD/status/1276245669372723200 [3] francesoir.fr/politique-monde/oxford-etude-recovery-ou-sont-les-morts
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6/3	Positive (see notes) POSITIVE	PEP	Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed)	A Randomized Trial of Hydroxych loroquine as Postexposure Prophylaxis for Covid-19
		COVID-19 cases are reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. PEP delayed treatment RCT. Cur..
6/3	Positive (see notes) POSITIVE	Post Exposure Prophylaxis study Source Study Page Post Exposure Prophylaxis study
		Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed)
		A Randomized Trial of Hydroxych loroquine as Postexposure Prophylaxis for Covid-19
		COVID-19 cases are reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. PEP delayed treatment RCT. Currently this is the only study where we have evaluated the result as positive while the authors indicate it is negative. We provide a detailed explanation of why the results presented here are positive [1]. Note that author comments also differ from the published conclusion. [1] c19study.com/boulware.html
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5/31	Positive POSITIVE	Early	Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed)	Azithromycin and Hydroxych loroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
		Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HC Q+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched pa..
5/31	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed)
		Azithromycin and Hydroxych loroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
		Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HC Q+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients.
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5/29	Positive POSITIVE	Late	Ayerbe et al., Journal of Thrombosis and Thrombolysis, doi: 10.1007/s11239-020-02162-z (Peer Reviewed)	The association between treatment with heparin and survival in patients with Covid-19
		2075 hospital patients in Spain. HC Q reduces mortality from 30% to 13%. Not adjusted for age and gender. HC Q group 10% more males and 6 years younger. Study primarily interested in Heparin.
5/29	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Ayerbe et al., Journal of Thrombosis and Thrombolysis, doi: 10.1007/s11239-020-02162-z (Peer Reviewed)
		The association between treatment with heparin and survival in patients with Covid-19
		2075 hospital patients in Spain. HC Q reduces mortality from 30% to 13%. Not adjusted for age and gender. HC Q group 10% more males and 6 years younger. Study primarily interested in Heparin.
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5/28	Positive POSITIVE	Late	Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint)	Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxych loroquine and azithromycin in Lebanon
		HC Q+AZ potentially explains 94.7% success in treating a fairly complex cohort.
5/28	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint)
		Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxych loroquine and azithromycin in Lebanon
		HC Q+AZ potentially explains 94.7% success in treating a fairly complex cohort.
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5/28	Positive POSITIVE	PrEP	Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed)	Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
		4+ doses of HC Q associated with a significant decline in the odds of getting infected, dose-response relationship exists.
5/28	Positive POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed)
		Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
		4+ doses of HC Q associated with a significant decline in the odds of getting infected, dose-response relationship exists.
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5/28	Positive POSITIVE	Late	Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed)	Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of ch loroquine for the treatment of COVID-19
		197 C Q patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
5/28	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed)
		Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of ch loroquine for the treatment of COVID-19
		197 C Q patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
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5/27	Meta META	Early	Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included in the study count)	Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
		Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy.
5/27	Meta META	Early treatment study Source Study Page Early treatment study
		Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included in the study count)
		Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
		Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy. Meta studies are not included in the percentages or study count.
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5/25	Negative NEGATIVE	Late	Ip et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint)	Hydroxych loroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
		Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HC Q during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]..
5/25	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Ip et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint)
		Hydroxych loroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
		Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HC Q during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HC Q alone (HR, 1.02 [95% CI, 0.83-1.27]), or HC Q+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HC Q during the study timeframe. Confounding by indication.
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5/22	Positive (advisory) POSITIVE	PEP, PrEP	ICMR, Indian Council of Medical Research (Advisory) (not included in the study count)	Revised advisory on the use of Hydroxych loroquine (HC Q) as prophylaxis for SARS-CoV-2 infection
		Healthcare workers on HC Q prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HC Q prophylaxis to asymptomatic household contacts of cases and fron..
5/22	Positive (advisory) POSITIVE	PEP, PrEP Source Study Page PEP, PrEP
		ICMR, Indian Council of Medical Research (Advisory) (not included in the study count)
		Revised advisory on the use of Hydroxych loroquine (HC Q) as prophylaxis for SARS-CoV-2 infection
		Healthcare workers on HC Q prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HC Q prophylaxis to asymptomatic household contacts of cases and frontline workers. Degree of benefit not quantified. Currently no formal study is available so this is not included in the study count.
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5/22	Retracted RETRACTED	Late	Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed)	Hydroxych loroquine or ch loroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
		Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
5/22	Retracted RETRACTED	Late treatment study Source Study Page Late treatment study
		Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed)
		Hydroxych loroquine or ch loroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
		Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
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5/20	Meta (negative) META	Late	Chacko et al., medRxiv, doi:10.1101/2020.05.14.20101774 (Preprint) (meta analysis - not included in the study count)	Hydroxych loroquine in COVID-19: A systematic review and meta-analysis
		Meta analysis not seeing a significant effect other than time to resolution of chest CT. Limited by heterogeneous nature of studies, baseline severity varied, most studies have a small sample size, endpoints reported at varying times, dos..
5/20	Meta (negative) META	Late treatment study Source Study Page Late treatment study
		Chacko et al., medRxiv, doi:10.1101/2020.05.14.20101774 (Preprint) (meta analysis - not included in the study count)
		Hydroxych loroquine in COVID-19: A systematic review and meta-analysis
		Meta analysis not seeing a significant effect other than time to resolution of chest CT. Limited by heterogeneous nature of studies, baseline severity varied, most studies have a small sample size, endpoints reported at varying times, dosage varied, and AZ, Zinc are not considered. Meta studies are not included in the percentages or study count.
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5/19	Negative NEGATIVE	Late	Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint)	Outcomes of Hydroxych loroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
		EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indic..
5/19	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint)
		Outcomes of Hydroxych loroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
		EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication.
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5/18	Positive POSITIVE	Late	Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint)	Treatment Response to Hydroxych loroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea
		Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HC Q+antibiotic. Preprint withdrawn pending peer review.
5/18	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint)
		Treatment Response to Hydroxych loroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea
		Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HC Q+antibiotic. Preprint withdrawn pending peer review.
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5/18	Positive POSITIVE	Early	Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint)	Doxycycline and Hydroxych loroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
		54 patients in long term care facilities. 6% death with HC Q+AZ compared to 22% using a naive indirect comparison.
5/18	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint)
		Doxycycline and Hydroxych loroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
		54 patients in long term care facilities. 6% death with HC Q+AZ compared to 22% using a naive indirect comparison.
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5/16	Inconc. INCONC.	PrEP	Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint)	Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxych loroquine therapy
		Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HC Q 0.5-4.0%, no-HC Q 0.4-2.7%). Confirmed cases were 1 HC
5/16	Inconc. INCONC.	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint)
		Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxych loroquine therapy
		Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HC Q 0.5-4.0%, no-HC Q 0.4-2.7%). Confirmed cases were 1 HC Q and 2 no-HC Q, confimed+likely cases were 1 HC Q and 3 no-HC Q. 1 HC Q and 2 no-HC Q patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. Further, there are very significant differences between the groups, for example 30% of the HC Q group have SLE vs. 2.5% of the no-HC Q group. SLE patients have a 5.7 times relative risk of pneumonia according to [1], whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower [2]. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence. [1] ncbi.nlm.nih.gov/pmc/articles/PMC4516647/ [2] academic.oup.com/rheumatology/article/52/1/53/1830871
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5/15	Positive POSITIVE	Late	Yu et al., Sci China Life Sci., 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed)	Low Dose of Hydroxych loroquine Reduces Fatality of Critically Ill Patients With COVID-19
		Retrospective, 550 critically ill patients. 19% fatality for HC Q versus 47% for non-HC Q.
5/15	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Yu et al., Sci China Life Sci., 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed)
		Low Dose of Hydroxych loroquine Reduces Fatality of Critically Ill Patients With COVID-19
		Retrospective, 550 critically ill patients. 19% fatality for HC Q versus 47% for non-HC Q.
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5/14	Negative NEGATIVE	Late	Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed)	Clinical efficacy of hydroxych loroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
		Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions [1]. None of the 15 patients receiving HC <..
5/14	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed)
		Clinical efficacy of hydroxych loroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
		Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions [1]. None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died compared to 23% overall. [1] bmj.com/content/369/bmj.m1844/rapid-responses
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5/11	Negative NEGATIVE	Late	Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed)	Association of Treatment With Hydroxych loroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
		Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [1] point out serious limitations that they say should be corrected on the record: patients receiving HC
5/11	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed)
		Association of Treatment With Hydroxych loroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
		Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [1] point out serious limitations that they say should be corrected on the record: patients receiving HC Q with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HC Q were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HC Q was associated with a significant survival benefit in a larger cohort of patients from New York City as reported by Mikami et al [2]. [1] ijidonline.com/article/S1201-9712(20)30604-4/fulltext [2] c19study.com/mikami.html
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5/10	Positive POSITIVE	Late	Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed)	A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection
		Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HC Q but p=0.12, OR 0.44 (0.16–1.24).
5/10	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed)
		A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection
		Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HC Q but p=0.12, OR 0.44 (0.16–1.24).
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5/8	Inconc. INCONC.	Late	Carlucci et al., doi:10.1101/2020.05.02.20080036 (Preprint)	Hydroxych loroquine and azithromycin plus zinc vs hydroxych loroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients
		Observational retrospective. Addition of Zinc to HC Q+AZ reduces mortality.
5/8	Inconc. INCONC.	Late treatment study Source Study Page Late treatment study
		Carlucci et al., doi:10.1101/2020.05.02.20080036 (Preprint)
		Hydroxych loroquine and azithromycin plus zinc vs hydroxych loroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients
		Observational retrospective. Addition of Zinc to HC Q+AZ reduces mortality.
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5/7	Theory THEORY	Theory	Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not included in the study count)	Excessive lysosomal ion-trapping of hydroxych loroquine and azithromycin
		Discusses pharmacokinetic properties of HC Q+AZ as a potential underlying mechanism of the observed antiviral effects.
5/7	Theory THEORY	Theory Source Study Page Theory
		Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not included in the study count)
		Excessive lysosomal ion-trapping of hydroxych loroquine and azithromycin
		Discusses pharmacokinetic properties of HC Q+AZ as a potential underlying mechanism of the observed antiviral effects.
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5/7	Inconc. INCONC.	Late	Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed)	Observational Study of Hydroxych loroquine in Hospitalized Patients with Covid-19
		There appears to be a major error in this paper. Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). This is not possible. Even if all propensity matched co..
5/7	Inconc. INCONC.	Late treatment study Source Study Page Late treatment study
		Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed)
		Observational Study of Hydroxych loroquine in Hospitalized Patients with Covid-19
		There appears to be a major error in this paper. Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). This is not possible. Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see [1]), this appears to invalidate the results. Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for late treatment. However, secondary analysis shows the success of HC Q was hidden by combining intubation and death - death / (combined death/intubation) for HC Q was 60% vs. control 89%, for details see: [2]. RCT recommended. No AZ or Zinc. HC Q group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics. [1] academic.oup.com/eurheartj/article/41/22/2058/5851436 [2] twitter.com/dperetti/status/1259154540630364162
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5/7	Positive (news) POSITIVE	N/A	Sermo (News) (not included in the study count)	Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-used therapies
		HC Q used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians.
5/7	Positive (news) POSITIVE	N/A Source Study Page N/A
		Sermo (News) (not included in the study count)
		Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-used therapies
		HC Q used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians. Currently no formal study is available so this is not included in the study count.
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5/6	Animal ANIMAL	Animal	Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count)	Hydroxych loroquine use against SARS-CoV-2 infection in non-human primates
		Monkey study which reports no effect of HC Q or HC Q+AZ. However, there are actually several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and contr..
5/6	Animal ANIMAL	Animal study Source Study Page Animal study
		Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count)
		Hydroxych loroquine use against SARS-CoV-2 infection in non-human primates
		Monkey study which reports no effect of HC Q or HC Q+AZ. However, there are actually several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and control monkeys. 58% reduction in lung lesions: the final day lung lesion data shows 63% of control monkeys have lesions, while 26% of treated monkeys do, p=0.095 (the final day data is missing for 7 monkeys, these are predicted based on the day 5 results and the trend of comparable monkeys). 97% increase in viral load recovery after one week: 3 of 8 control monkeys (38%) have recovered with <= 4 log10 copies/mL viral load, compared to 17 of 23 treated monkeys (74%), p=0.095. 3 of 8 (38%) control monkeys also have a higher peak viral load than 100% of the 23 treated monkeys post-treatment. The group with the lowest peak viral load is the PrEP group. All animals were infected with the same initial viral load, whereas real-world infections vary in the initial viral load, and lower inital viral loads allow greater time to mount an immune response.
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5/5	Positive POSITIVE	Late	Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint)	Early Hydroxych loroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study
		166 patients hospitalised with COVID-19, HC Q increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients relatively serious condition.
5/5	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint)
		Early Hydroxych loroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study
		166 patients hospitalised with COVID-19, HC Q increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients relatively serious condition.
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5/5	Positive POSITIVE	Early, Late	Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed)	Early Treatment of COVID-19 Patients With Hydroxych loroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France
		Retrospective 1061 patients. HC Q+AZ safe and results in a low fatality rate.
5/5	Positive POSITIVE	Early, Late Source Study Page Early, Late
		Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed)
		Early Treatment of COVID-19 Patients With Hydroxych loroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France
		Retrospective 1061 patients. HC Q+AZ safe and results in a low fatality rate.
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5/5	Inconc. INCONC.	PrEP	Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed)	Continuous Hydroxych loroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis
		Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HC Q patient cases. Only considers people tested at a time when primarily symptomatic cases..
5/5	Inconc. INCONC.	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed)
		Continuous Hydroxych loroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis
		Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HC Q patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Note that patients with SLE, RA, and other autoimmune conditions have a significantly increased susceptibility to and incidence of infections [1, 2, 3, 4, 5, 6, 7], with this context the results suggest HC Q is effective, but this is still inconclusive with the small sample size. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence. [1] pubmed.ncbi.nlm.nih.gov/27370880/ [2] pubmed.ncbi.nlm.nih.gov/8778988/ [3] pubmed.ncbi.nlm.nih.gov/23192911/ [4] pubmed.ncbi.nlm.nih.gov/11447699/ [5] pubmed.ncbi.nlm.nih.gov/30954968/ [6] advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-019-0055-y [7] ncbi.nlm.nih.gov/pmc/articles/PMC6099129/
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5/1	Safety SAFETY	N/A	Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count)	Risk of QT Interval Prolongation Associated With Use of Hydroxych loroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)
		Study of 90 hospitalized patients given HC Q, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HC Q, and 442ms for HC Q+AZ. Medi..
5/1	Safety SAFETY	N/A Source Study Page N/A
		Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count)
		Risk of QT Interval Prolongation Associated With Use of Hydroxych loroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)
		Study of 90 hospitalized patients given HC Q, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HC Q, and 442ms for HC Q+AZ. Median change for HC Q+AZ ΔQTc of 23ms vs. 5.5ms for HC Q. Other factors such as stress cardiomyopathy or myocarditis could not be ruled out. Without a control arm, they could not conclude that HC Q and AZ conferred increased cardiotoxic risk; however, compared with HC Q alone, ΔQTc differences were likely associated with the addition of AZ. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics or had a baseline QTc of 450 milliseconds or more. HC Q was discontinued in 10 patients due to adverse events including nausea, hypoglycemia, and 1 case of torsades de pointes. There were no deaths reported. Appropriate use and careful analysis of contraindications, risks, and benefits are important. More recent and much larger studies have not shown significant safety concerns, including outpatient RCTs showing no serious adverse events, and even the RECOVERY trial which used an unusually high dose of HC Q (including 237 patients also receiving AZ) reports they "did not show any excess in ventricular tachycardia (including torsade de pointes) or ventricular fibrillation in the hydroxych loroquine arm", and "serious cardiovascular toxicity has been reported very rarely despite the high prevalence of cardiovascular disease in hospitalized patients, the common occurrence of myocarditis in COVID-19, and the extensive use of hydroxych loroquine and azithromycin together."
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5/1	Safety SAFETY	N/A	Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count)	Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxych loroquine Alone or in Combination With Azithromycin in an Intensive Care Unit
		Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HC Q with or w/o AZ was given to 4..
5/1	Safety SAFETY	N/A Source Study Page N/A
		Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count)
		Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxych loroquine Alone or in Combination With Azithromycin in an Intensive Care Unit
		Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HC Q with or w/o AZ was given to 45% and 55% respectively. They showed an increase in QTc, more significant with the combination of HC Q+AZ where prolonged QTc was observed in 36% (10 with ΔQTc >60 milliseconds and 7 with QTc ≥500 milliseconds). No ventricular arrhythmia, including torsades de pointes, was recorded. While these results may not be generalizable outside the ICU, caution is recommended in use, especially with the combination. Appropriate use and careful analysis of contraindications, risks, and benefits are important. More recent and much larger studies have not shown significant safety concerns, including outpatient RCTs showing no serious adverse events, and even the RECOVERY trial which used an unusually high dose of HC Q (including 237 patients also receiving AZ) reports they "did not show any excess in ventricular tachycardia (including torsade de pointes) or ventricular fibrillation in the hydroxych loroquine arm", and "serious cardiovascular toxicity has been reported very rarely despite the high prevalence of cardiovascular disease in hospitalized patients, the common occurrence of myocarditis in COVID-19, and the extensive use of hydroxych loroquine and azithromycin together."
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5/2	Positive (news) POSITIVE	Late	Seydi (News) (not included in the study count)	Coronavirus: a study in Senegal confirms the effectiveness of hydroxych loroquine
		Preliminary results of Senegal trial with 181 patients showing faster recovery with HC Q, and even faster recovery with HC Q+AZ.
5/2	Positive (news) POSITIVE	Late treatment study Source Study Page Late treatment study
		Seydi (News) (not included in the study count)
		Coronavirus: a study in Senegal confirms the effectiveness of hydroxych loroquine
		Preliminary results of Senegal trial with 181 patients showing faster recovery with HC Q, and even faster recovery with HC Q+AZ. Currently no formal study is available so this is not included in the study count.
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4/30	Positive POSITIVE	Early	Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed)	Efficacy of ch loroquine and hydroxych loroquine in the treatment of COVID-19
		Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that C Q/HC Q (widely used for malaria) are pr..
4/30	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed)
		Efficacy of ch loroquine and hydroxych loroquine in the treatment of COVID-19
		Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that C Q/HC Q (widely used for malaria) are protective for COVID-19. This paper also includes a review of 9 articles supporting the efficacy of HC Q and C Q.
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4/29	Safety SAFETY	N/A	Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed)	The Effect of Ch loroquine, Hydroxych loroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection
		201 hospitalized patients. No serious side effects of HC Q. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, c..
4/29	Safety SAFETY	N/A Source Study Page N/A
		Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed)
		The Effect of Ch loroquine, Hydroxych loroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection
		201 hospitalized patients. No serious side effects of HC Q. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, clinicians seldom need to discontinue therapy.
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4/25	In Vitro IN VITRO	In Vitro	Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count)	In vitro testing of combined hydroxych loroquine and azithromycin on SARS-CoV-2 shows synergistic effect
		HC Q and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
4/25	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count)
		In vitro testing of combined hydroxych loroquine and azithromycin on SARS-CoV-2 shows synergistic effect
		HC Q and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
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4/24	Inconc. INCONC.	Early	Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint)	COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes
		Small limited trial with 100 patients concluding that HC Q improved clinical outcome.
4/24	Inconc. INCONC.	Early treatment study Source Study Page Early treatment study
		Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint)
		COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes
		Small limited trial with 100 patients concluding that HC Q improved clinical outcome.
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4/21	Positive POSITIVE	Early	Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint)	Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths
		Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]C Q, showing dramatically lower death in [H]C Q countries. This paper does not at..
4/21	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint)
		Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths
		Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]C Q, showing dramatically lower death in [H]C Q countries. This paper does not attempt to account for population age and other differences between the countries and recommends further study.
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4/21	Negative NEGATIVE	Late	Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed)	Outcomes of hydroxych loroquine usage in United States veterans hospitalized with Covid-19
		Retrospective 368 hospitalized patients, no significant reduction in mortality or the need for mechanical ventilation with HC Q or HC Q+AZ. Study notes HC Q was more likely..
4/21	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed)
		Outcomes of hydroxych loroquine usage in United States veterans hospitalized with Covid-19
		Retrospective 368 hospitalized patients, no significant reduction in mortality or the need for mechanical ventilation with HC Q or HC Q+AZ. Study notes HC Q was more likely to be prescribed to patients with more severe disease.
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4/17	Positive POSITIVE	PEP	Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed)	Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals?
		Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases after 14 days.
4/17	Positive POSITIVE	Post Exposure Prophylaxis study Source Study Page Post Exposure Prophylaxis study
		Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed)
		Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals?
		Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases after 14 days.
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4/16	Negative NEGATIVE	Late	Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed)	Ch loroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)
		Increased incidence of prolonged QT and death in high dose treatment arm. Patients >75 only enrolled in high dose arm, age of high dose arm significantly higher than low dose arm (p=0.02). Very sick at baseline, 43% in ICU, 88.9% on respi..
4/16	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed)
		Ch loroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)
		Increased incidence of prolonged QT and death in high dose treatment arm. Patients >75 only enrolled in high dose arm, age of high dose arm significantly higher than low dose arm (p=0.02). Very sick at baseline, 43% in ICU, 88.9% on respiratory therapy prior to treatment.
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4/15	Positive POSITIVE	Early	Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint)	Empirical treatment with hydroxych loroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine
		636 patients. HC Q+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
4/15	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint)
		Empirical treatment with hydroxych loroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine
		636 patients. HC Q+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
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4/15	Theory THEORY	Theory	Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count)	Hyperglycemia, hydroxych loroquine, and the COVID‐19 pandemic
		Theory on the effectiveness of HC Q. HC Q has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of pr..
4/15	Theory THEORY	Theory Source Study Page Theory
		Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count)
		Hyperglycemia, hydroxych loroquine, and the COVID‐19 pandemic
		Theory on the effectiveness of HC Q. HC Q has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of proteins involved in the humoral immune response, possibly including the macrophage FcR gamma IgG receptor and other immunomodulatory proteins, potentially through inhibition of UDP‐N‐acetylglucosamine 2‐epimerase. In combination with potential other immunomodulatory effects, this could possibly blunt the progression of COVID‐19 pneumonia all to way up to ARDS.
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4/14	Negative NEGATIVE	Late	Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed)	Hydroxych loroquine in patients with COVID-19: an open-label, randomized, controlled trial
		150 patients very late stage RCT. No significant difference. More symptomatic relief with HC Q. Treatment very late, average 16.6 days after symptom onset. Data favorable to HC Q was deleted in ..
4/14	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed)
		Hydroxych loroquine in patients with COVID-19: an open-label, randomized, controlled trial
		150 patients very late stage RCT. No significant difference. More symptomatic relief with HC Q. Treatment very late, average 16.6 days after symptom onset. Data favorable to HC Q was deleted in the second version, see analysis [1]. [1] mediterranee-infection.com/tang-et-al-bmj-donnees-favorables-a-lhydroxychloroquine-supprimees/
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4/13	Positive POSITIVE	Late	Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Peer Reviewed)	Update on Use of Ch loroquine/Hydroxych loroquine to Treat Coronavirus Disease 2019 (COVID-19)
		Increasing evidence from completed clinical studies shows C Q and HC Q effective (HC Q more effective).
4/13	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Peer Reviewed)
		Update on Use of Ch loroquine/Hydroxych loroquine to Treat Coronavirus Disease 2019 (COVID-19)
		Increasing evidence from completed clinical studies shows C Q and HC Q effective (HC Q more effective).
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4/12	Negative NEGATIVE	Late	Barbosa et al., Preprint (Preprint)	Clinical outcomes of hydroxych loroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study
		Small retrospective study with 63 patients (32 treated with HC Q), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been publishe..
4/12	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Barbosa et al., Preprint (Preprint)
		Clinical outcomes of hydroxych loroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study
		Small retrospective study with 63 patients (32 treated with HC Q), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later.
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4/11	Positive POSITIVE	Early	Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed)	Clinical and microbiological effect of a combination of hydroxych loroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study
		Pilot study suggesting improvement with HC Q+AZ and recommending further study.
4/11	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed)
		Clinical and microbiological effect of a combination of hydroxych loroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study
		Pilot study suggesting improvement with HC Q+AZ and recommending further study.
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4/10	Meta (negative) META	Late	Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in the study count)	Quantifying treatment effects of hydroxych loroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020)
		Secondary analysis of Gautret et al. showing "modest to no impact of HC Q treatment, with more significant effects from [HC Q+AZ]".
4/10	Meta (negative) META	Late treatment study Source Study Page Late treatment study
		Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in the study count)
		Quantifying treatment effects of hydroxych loroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020)
		Secondary analysis of Gautret et al. showing "modest to no impact of HC Q treatment, with more significant effects from [HC Q+AZ]". Meta studies are not included in the percentages or study count.
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4/1	Positive POSITIVE	Late	Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed)	Treating COVID-19 with Ch loroquine
		22 patients. All C Q patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for C Q vs. 6.5 days for Lopinavir/Rotinavir.
4/1	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed)
		Treating COVID-19 with Ch loroquine
		22 patients. All C Q patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for C Q vs. 6.5 days for Lopinavir/Rotinavir.
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3/31	Positive POSITIVE	Late	Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint)	Efficacy of hydroxych loroquine in patients with COVID-19: results of a randomized clinical trial
		62 patients. RCT showing significantly faster recovery with HC Q. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% ..
3/31	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint)
		Efficacy of hydroxych loroquine in patients with COVID-19: results of a randomized clinical trial
		62 patients. RCT showing significantly faster recovery with HC Q. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patients and 16% of control patients.
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3/31	In Vitro IN VITRO	In Vitro	Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study count)	Combined Prophylactic and Therapeutic Use Maximizes Hydroxych loroquine Anti-SARS-CoV-2 Effects in vitro
		In vitro study, not included in the study count or percentages, showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells.
3/31	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study count)
		Combined Prophylactic and Therapeutic Use Maximizes Hydroxych loroquine Anti-SARS-CoV-2 Effects in vitro
		In vitro study, not included in the study count or percentages, showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells.
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3/28	Negative NEGATIVE	Late	Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter)	No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxych loroquine and azithromycin in patients with severe COVID-19 infection
		11 patients with severe cases. No evidence of benefit for HC Q.
3/28	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter)
		No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxych loroquine and azithromycin in patients with severe COVID-19 infection
		11 patients with severe cases. No evidence of benefit for HC Q.
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3/26	Positive (news) POSITIVE	Late	Zhong Nanshan (钟南山) (News) (not included in the study count)	Efficacy and safety of ch loroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial
		197 patients. HC Q effective. Viral RNA negative in 95.9% versus 79.6% control. Median time to negative tests 3 days versus 9 days for control.
3/26	Positive (news) POSITIVE	Late treatment study Source Study Page Late treatment study
		Zhong Nanshan (钟南山) (News) (not included in the study count)
		Efficacy and safety of ch loroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial
		197 patients. HC Q effective. Viral RNA negative in 95.9% versus 79.6% control. Median time to negative tests 3 days versus 9 days for control. Currently no formal study is available so this is not included in the study count.
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3/24	Theory THEORY	Theory	Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory)	Is Hydroxych loroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19?
		C Q and HC Q inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on ..
3/24	Theory THEORY	Theory Source Study Page Theory
		Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory)
		Is Hydroxych loroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19?
		C Q and HC Q inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on safety.
		Source Study Page Share Tweet Submit Corrections or Comments
3/23	Theory THEORY	Theory	Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer Reviewed) (Theory) (not included in the study count)	Insights from nanomedicine into ch loroquine efficacy against COVID-19
		C Q is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
3/23	Theory THEORY	Theory Source Study Page Theory
		Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer Reviewed) (Theory) (not included in the study count)
		Insights from nanomedicine into ch loroquine efficacy against COVID-19
		C Q is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
		Source Study Page Share Tweet Submit Corrections or Comments
3/21	Positive (advisory) POSITIVE	PrEP	ICMR, Indian Council of Medical Research (Advisory) (not included in the study count)	Advisory on the use of hydroxy-ch loroquine as prophylaxis for SARS-CoV-2 infection
		Recommends HC Q for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo.
3/21	Positive (advisory) POSITIVE	Pre-Exposure Prophylaxis study Source Study Page Pre-Exposure Prophylaxis study
		ICMR, Indian Council of Medical Research (Advisory) (not included in the study count)
		Advisory on the use of hydroxy-ch loroquine as prophylaxis for SARS-CoV-2 infection
		Recommends HC Q for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo. Currently no formal study is available so this is not included in the study count.
		Source Study Page Share Tweet Submit Corrections or Comments
3/20	Positive (news) POSITIVE	Late	Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count)	Shanghai Experience of COVID-19 Management
		Clinical studies of HC Q with 184 cases and 21 hospitals show HC Q is effective.
3/20	Positive (news) POSITIVE	Late treatment study Source Study Page Late treatment study
		Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count)
		Shanghai Experience of COVID-19 Management
		Clinical studies of HC Q with 184 cases and 21 hospitals show HC Q is effective. Currently no formal study is available so this is not included in the study count.
		Source Study Page Share Tweet Submit Corrections or Comments
3/18	In Vitro IN VITRO	In Vitro	Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count)	Hydroxych loroquine, a less toxic derivative of ch loroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
		HC Q effective in vitro and less toxic than C Q. In addition to direct antiviral activity, HC Q is a safe and successful anti-inflammatory agent that has been used extensiv..
3/18	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count)
		Hydroxych loroquine, a less toxic derivative of ch loroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
		HC Q effective in vitro and less toxic than C Q. In addition to direct antiviral activity, HC Q is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors. Therefore, in COVID-19 patients, HC Q may also contribute to attenuating the inflammatory response. Careful design of clinical trials is important to achieve efficient and safe control of the infection.
		Source Study Page Share Tweet Submit Corrections or Comments
3/17	Positive POSITIVE	Early	Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed)	Hydroxych loroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial
		HC Q significantly associated with viral load reduction / elimination, enhanced with AZ. This early and small trial has significant limitations, larger and more recent trials by the same group confirm the results.
3/17	Positive POSITIVE	Early treatment study Source Study Page Early treatment study
		Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed)
		Hydroxych loroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial
		HC Q significantly associated with viral load reduction / elimination, enhanced with AZ. This early and small trial has significant limitations, larger and more recent trials by the same group confirm the results.
		Source Study Page Share Tweet Submit Corrections or Comments
3/17	Review REVIEW	N/A	Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Peer Reviewed) (not included in the study count)	Aminoquinolines against coronavirus disease 2019 (COVID-19): ch loroquine or hydroxych loroquine
		Discussion of mechanisms of action, C Q vs. HC Q, early studies, safety.
3/17	Review REVIEW	N/A Source Study Page N/A
		Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Peer Reviewed) (not included in the study count)
		Aminoquinolines against coronavirus disease 2019 (COVID-19): ch loroquine or hydroxych loroquine
		Discussion of mechanisms of action, C Q vs. HC Q, early studies, safety.
		Source Study Page Share Tweet Submit Corrections or Comments
3/13	Review REVIEW	N/A	Todaro and Rigano (Preprint) (not included in the study count)	An Effective Treatment for Coronavirus (COVID-19)
		Discussion of existing research, treatment guidelines, and mechanisms of action for C Q and HC Q, recommending use.
3/13	Review REVIEW	N/A Source Study Page N/A
		Todaro and Rigano (Preprint) (not included in the study count)
		An Effective Treatment for Coronavirus (COVID-19)
		Discussion of existing research, treatment guidelines, and mechanisms of action for C Q and HC Q, recommending use.
		Source Study Page Share Tweet Submit Corrections or Comments
3/12	Theory THEORY	Theory	Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count)	New insights on the antiviral effects of ch loroquine against coronavirus: what to expect for COVID-19?
		Discusses mechanisms of C Q interference with the SARS-CoV-2 replication cycle.
3/12	Theory THEORY	Theory Source Study Page Theory
		Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count)
		New insights on the antiviral effects of ch loroquine against coronavirus: what to expect for COVID-19?
		Discusses mechanisms of C Q interference with the SARS-CoV-2 replication cycle.
		Source Study Page Share Tweet Submit Corrections or Comments
3/10	Meta (positive) META	N/A	Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in the study count)	A Systematic Review on the Efficacy and Safety of Ch loroquine for the Treatment of COVID-19
		Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI.
3/10	Meta (positive) META	N/A Source Study Page N/A
		Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in the study count)
		A Systematic Review on the Efficacy and Safety of Ch loroquine for the Treatment of COVID-19
		Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI. Meta studies are not included in the percentages or study count.
		Source Study Page Share Tweet Submit Corrections or Comments
3/9	In Vitro IN VITRO	N/A	Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (not included in the study count)	In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxych loroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
		HC Q is more potent than C Q in vitro for inhibiting SARS-CoV-2. Simulates HC Q concentration in lung fluid and provides dosing recommendations.
3/9	In Vitro IN VITRO	N/A Source Study Page N/A
		Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (not included in the study count)
		In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxych loroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
		HC Q is more potent than C Q in vitro for inhibiting SARS-CoV-2. Simulates HC Q concentration in lung fluid and provides dosing recommendations.
		Source Study Page Share Tweet Submit Corrections or Comments
3/6	Negative NEGATIVE	Late	Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed)	A pilot study of hydroxych loroquine in treatment of patients with common coronavirus disease-19 (COVID-19)
		30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HC Q but not statistically significant. One HC Q patient developed to ..
3/6	Negative NEGATIVE	Late treatment study Source Study Page Late treatment study
		Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed)
		A pilot study of hydroxych loroquine in treatment of patients with common coronavirus disease-19 (COVID-19)
		30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HC Q but not statistically significant. One HC Q patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.
		Source Study Page Share Tweet Submit Corrections or Comments
3/4	Positive POSITIVE	Late	Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Peer Reviewed)	Ch loroquine and Hydroxych loroquine as Available Weapons to Fight COVID-19
		Recommending C Q and HC Q for COVID-19 based on 20 clinical studies in China and a strong rationale for use.
3/4	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Peer Reviewed)
		Ch loroquine and Hydroxych loroquine as Available Weapons to Fight COVID-19
		Recommending C Q and HC Q for COVID-19 based on 20 clinical studies in China and a strong rationale for use.
		Source Study Page Share Tweet Submit Corrections or Comments
2/20	Positive POSITIVE	Late	Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed)	Expert Consensus on Ch loroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia
		Early trials in China show C Q results in shorter hospital stays and improved patient outcomes.
2/20	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed)
		Expert Consensus on Ch loroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia
		Early trials in China show C Q results in shorter hospital stays and improved patient outcomes.
		Source Study Page Share Tweet Submit Corrections or Comments
2/19	Positive POSITIVE	Late	Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed)	Breakthrough: Ch loroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies
		Results from 15 clinical trials in China showing C Q is effective.
2/19	Positive POSITIVE	Late treatment study Source Study Page Late treatment study
		Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed)
		Breakthrough: Ch loroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies
		Results from 15 clinical trials in China showing C Q is effective.
		Source Study Page Share Tweet Submit Corrections or Comments
2/17	Positive (news) POSITIVE	Late	Sun Yanrong, deputy head of the China National Center for Biotechnology Development (News) (not included in the study count)	Antimalarial drug confirmed effective on COVID-19
		HC Q under clinical trials in >10 hospitals in China and has shown fairly good efficacy.
2/17	Positive (news) POSITIVE	Late treatment study Source Study Page Late treatment study
		Sun Yanrong, deputy head of the China National Center for Biotechnology Development (News) (not included in the study count)
		Antimalarial drug confirmed effective on COVID-19
		HC Q under clinical trials in >10 hospitals in China and has shown fairly good efficacy. Currently no formal study is available so this is not included in the study count.
		Source Study Page Share Tweet Submit Corrections or Comments
2/4	In Vitro IN VITRO	In Vitro	Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count)	Remdesivir and ch loroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
		In vitro study, not included in the study count or percentages. Remdesivir and C Q potently blocked virus infection in vitro.
2/4	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count)
		Remdesivir and ch loroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
		In vitro study, not included in the study count or percentages. Remdesivir and C Q potently blocked virus infection in vitro.
		Source Study Page Share Tweet Submit Corrections or Comments
2014	In Vitro IN VITRO	In Vitro	de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the study count)	Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture
		C Q inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range.
2014	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the study count)
		Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture
		C Q inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range.
		Source Study Page Share Tweet Submit Corrections or Comments
2012	Animal ANIMAL	Animal	Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count)	Anti-malaria drug ch loroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model
		C Q, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus.
2012	Animal ANIMAL	Animal study Source Study Page Animal study
		Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count)
		Anti-malaria drug ch loroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model
		C Q, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus.
		Source Study Page Share Tweet Submit Corrections or Comments
2009	Animal ANIMAL	Animal	Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study count)	Antiviral Activity of Ch loroquine against Human Coronavirus OC43 Infection in Newborn Mice
		C Q inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with C Q acquired transplacentally or via maternal milk. The highest survi..
2009	Animal ANIMAL	Animal study Source Study Page Animal study
		Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study count)
		Antiviral Activity of Ch loroquine against Human Coronavirus OC43 Infection in Newborn Mice
		C Q inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with C Q acquired transplacentally or via maternal milk. The highest survival rate (98.6%) was found when mother mice were treated daily with a concentration of 15 mg of C Q per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg C Q and 13% survival when treated with 1 mg/kg C Q. C Q can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs.
		Source Study Page Share Tweet Submit Corrections or Comments
2008	In Vitro IN VITRO	In Vitro	Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included in the study count)	Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by ch loroquine: Involvement of p38 MAPK and ERK
		C Q significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. C Q affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracell..
2008	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included in the study count)
		Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by ch loroquine: Involvement of p38 MAPK and ERK
		C Q significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. C Q affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). p38 MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral replication.
		Source Study Page Share Tweet Submit Corrections or Comments
2006	In Vitro IN VITRO	In Vitro	Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count)	New insights into the antiviral effects of ch loroquine
		Update to 2003 paper, not included in the study count or percentages. Hypothesis of C Q inhibiting SARS replication has been confirmed in two in-vitro studies. C Q affected an early stage of SAR..
2006	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count)
		New insights into the antiviral effects of ch loroquine
		Update to 2003 paper, not included in the study count or percentages. Hypothesis of C Q inhibiting SARS replication has been confirmed in two in-vitro studies. C Q affected an early stage of SARS replication.
		Source Study Page Share Tweet Submit Corrections or Comments
2005	In Vitro IN VITRO	In Vitro	Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count)	Ch loroquine is a potent inhibitor of SARS coronavirus infection and spread
		In vitro study, SARS-CoV-1, not included in the study count or percentages. C Q has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treat..
2005	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count)
		Ch loroquine is a potent inhibitor of SARS coronavirus infection and spread
		In vitro study, SARS-CoV-1, not included in the study count or percentages. C Q has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treatment use. Describes three mechanisms by which the drug might work and suggests it may have both a prophylactic and therapeutic role in coronavirus infections.
		Source Study Page Share Tweet Submit Corrections or Comments
2004	In Vitro IN VITRO	In Vitro	Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included in the study count)	In vitro inhibition of severe acute respiratory syndrome coronavirus by ch loroquine
		In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of C Q for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inh..
2004	In Vitro IN VITRO	In Vitro Source Study Page In Vitro
		Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included in the study count)
		In vitro inhibition of severe acute respiratory syndrome coronavirus by ch loroquine
		In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of C Q for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inhibition of SARS-CoV in vitro approximates the plasma concentrations of C Q reached during treatment of acute malaria. C Q may be considered for immediate use in the prevention and treatment of SARS-CoV infections.
		Source Study Page Share Tweet Submit Corrections or Comments
2003	Theory THEORY	Theory	Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count)	Effects of ch loroquine on viral infections: an old drug against today's diseases
		Not included in the study count or percentages. Discussion/review noting that C Q exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coron..
2003	Theory THEORY	Theory Source Study Page Theory
		Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count)
		Effects of ch loroquine on viral infections: an old drug against today's diseases
		Not included in the study count or percentages. Discussion/review noting that C Q exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Notes that C Q has immunomodulatory effects, suppressing the production/release of tumour necrosis factor α and interleukin 6, which mediate the inflammatory complications of several viral diseases.
		Source Study Page Share Tweet Submit Corrections or Comments
1889	Inconc. (news) INCONC.	N/A	Edwin Wiley Grove (News) (not included in the study count)	Laxative Bromo Quinine
		Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an interesting observation.
1889	Inconc. (news) INCONC.	N/A Source Study Page N/A
		Edwin Wiley Grove (News) (not included in the study count)
		Laxative Bromo Quinine
		Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an interesting observation.
		Source Study Page Share Tweet Submit Corrections or Comments

Note: In Vitro, Meta, Theory, Safety, Review, News, and Retracted items are not included in the percentages and study count. There is a total of 117 items. Positive/negative effects vary in degree and certainty, please read the papers or descriptions thereof for more details. Every study has some limitations when considered in isolation (for example confounding factors; sub-optimal treatment regimens; dosing regimens that may be too low, too high, or insufficiently account for the long half-life of HCQ; large treatment delays; small sample sizes; lack of focus on severity; reliance on Internet surveys; and patient characteristics very different from the most at-risk population).

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