State of Ohio Bans Doctors from using Hydroychloroquine--Governor Reverses Order Next Day After Tremendous Attention Focused on It

On July 29, Ohio's Pharmacy Board announced that beginning the following day, neither chloroquine drug could be dispensed to prevent or treat Covid-19. Prescriptions would require a diagnosis and those for Covid would be rejected.  Not only that, if a prescriber happened to have obtained the drug and wished to provide it to to a patient, they were not allowed to do so.

The morning of July 30, after a massive overnight twitterfest about this action, FDA Commissioner Hahn was interviewed on the Today show and said that drug prescribing was a matter between a doctor and a patient. Shortly thereafter, Ohio's governor withdrew the regulation, citing Commissioner Hahn.

The Oregon Pharmacy Board had issued a similar rule on June 15, which was withdrawn on July 14, after it too drew public attention.

No physician association has supported these restrictions on physician prescribing; the system simply did an end run around them, pulling on the levers it had at its disposal.

The Politics of Hydroxychloroquine. The FDA has suspended a permit for its use. Let doctors decide/ WSJ

Below is a Wall Street Journal article I am reposting in full--Nass

https://www.wsj.com/articles/the-politics-of-hydroxychloroquine-11594831408

OPINION | COMMENTARY
The Politics of Hydroxychloroquine
Trump touted it, so Biden denounces it. The FDA has suspended a permit for its use. Let doctors decide.

By Allysia Finley
July 15, 2020 12:43 pm ET

Hubert Humphrey began his career as a pharmacist before going into politics. Today’s politicians sometimes seem to have the opposite aspiration. President Trump “pushes dangerous, disproven drugs,” Joe Biden declares in his “Plan to Beat Covid-19.” “Our country is now stuck with a massive stockpile of hydroxychloroquine, a drug Trump repeatedly hailed.”

Neither man has any expertise in pharmacology, and Mr. Trump did get out over his skis in promoting the malaria treatment, also known as HCQ, for the novel coronavirus. But since every Trump action prompts a reaction, his political and media opponents launched a campaign to discredit the drug. This politicized environment has produced dubious science and erratic policy.
The Food and Drug Administration issued an emergency use authorization on March 28, allowing hospitals to treat Covid-19 patients outside clinical trials using HCQ donated by manufacturers to the national stockpile. But on June 15 the agency rescinded the authorization. “In light of ongoing serious cardiac adverse events and other potential serious side effects,” the FDA announced, “the known and potential benefits of . . . hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
But the scientific basis for the revocation now appears faulty. Most studies didn’t adjust results for confounding variables such as disease severity, drug dosage or when patients

started treatment. Two new peer-reviewed studies find that HCQ can significantly reduce mortality in hospitalized patients. With hospital beds filling up across the American South and West and a limited supply of Gilead Sciences ’ antiviral remdesivir, the FDA should reinstate its emergency-use authorization for HCQ.
HCQ has been safely used for decades to treat patients with lupus and rheumatoid arthritis, both inflammatory autoimmune conditions. The drug has also been found to interfere with the

novel coronavirus’s replication in vitro, and studies this spring from France, Brazil and China showed the drug might help moderately ill patients.

HCQ also has side effects. It can cause cardiac arrhythmias, a particular risk for severely ill Covid-19 patients because the virus can damage heart tissue. But the FDA emergency authorization warned about this and required doctors to monitor patients closely and report adverse side effects to the agency.

In late May, the Lancet published a large-scale international study that claimed hospitalized Covid-19 patients treated with HCQ were 30% more likely to die. But the medical journal retracted the study on June 4 after more than 120 scientists pointed out significant flaws in the data and methodology. The source of the raw data refused to share it with independent reviewers.

Nonetheless, the anti-Trump media claimed vindication later that day when the New England Journal of Medicine published a randomized trial that concluded HCQ didn’t prevent illness in people who had been exposed to the virus. The study’s raw data showed that people who took HCQ within two days of exposure were 38% less likely to develop symptoms. But a third of subjects in the trial took the drug four days after exposure, which obscured its benefits. Since the average viral incubation period is five days, starting the drug four days after exposure is unlikely to do much good.

On June 5, University of Oxford researchers reported that a midpoint review of their HCQ trial had found no clinical benefit. “This result should change medical practice worldwide,” Oxford epidemiologist Martin Landray declared in a press release. It usually pays to be skeptical of such sweeping claims based on a single study.

The Oxford team released a preprint study with more data from its trial on Wednesday. Patients were treated on average nine days after their symptom onset, which may have been too late to improve clinical outcomes. The trial’s protocol also called for dosages two to three times as high as those recommended by the FDA’s emergency use authorization.

In revoking the authorization 10 days later, the FDA cited the New England Journal and Oxford work as well as a British Medical Journal study from China that purportedly found no benefit from the drug. Yet an April draft of the last study concluded that HCQ accelerated “the alleviation of clinical symptoms, possibly through anti-inflammatory properties” and “might prevent disease progression, particularly in patients at higher risk.”

The draft also noted that after adjusting for the confounding effects of other antivirals used to treat patients, “the efficacy of HCQ on the alleviation of symptoms was more evident.” This analysis of HCQ’s benefits was scrubbed from the published version because some editors and reviewers quibbled that it wasn’t called for in the trial protocol.

The first of the new studies showing benefits from HCQ appeared in the Journal of General Internal Medicine on June 30. It found patients treated with the drug at New York’s Mount Sinai Health System hospitals were 47% less likely to die after adjusting for confounding variables such as underlying health conditions and disease severity. Notably, Mount Sinai’s treatment protocol called for lower dosages than in the Oxford trial, and patients on average were treated within one day of hospitalization.

The second, published July 1 in the International Journal of Infectious Diseases, found that patients treated with HCQ at Henry Ford Health System hospitals in Detroit were 50% to 66% less likely to die after adjusting for confounding variables including other treatments. Nearly all patients began treatment within two days of admission, received dosages that hewed closely to FDA guidelines, and were continuously monitored for cardiac arrhythmias.

“Our patient population received aggressive early medical intervention, and were less prone to development of myocarditis, and cardiac inflammation commonly seen in later stages of COVID-19 disease,” the Henry Ford doctors noted.

This shouldn’t be surprising. An FDA safety review published July 1 reported only five adverse side effects from HCQ through the emergency use authorization among tens of millions of doses that were distributed to hospitals. This suggests that the drug isn’t harmful to the vast majority of patients who are treated according to FDA guidelines.

With hundreds of Covid-infected Americans still dying each day, the agency should let physicians decide whether to treat patients with HCQ based on their experience and scientific evidence. Leave politics out of it.

Ms. Finley is a member of the Journal’s editorial board.

Deaths in the entire United States "involving Covid" equal the number of deaths in NYC at its peak/ CDC

The CDC provides updated US death data on 7/24/20 "involving Covid" (2nd column) @ https://www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm

Deaths in the US have been FLAT or DECREASING over the last five weeks. Why aren't you hearing this? Because the media want to instill panic so they talk about rising cases (many asymptomatic, based on often inaccurate lab tests).  We are not having "3 New Yorks" as Dr. Birx claimed.  The fact is that the entire US is now having as many deaths per week as New York City had during its peak in early April.  
Got that?  The entire US equals ONE New York.  See CDC data below. 

Table 1. Deaths involving coronavirus disease 2019 (COVID-19), pneumonia, and influenza reported to NCHS by week ending date, United States. Week ending 2/1/2020 to 8/1/2020.*

Updated Aug 4, 2020

Week ending date in which the death occurred	All Deaths involving COVID-19 (U07.1)1	Deaths from All Causes	Percent of Expected Deaths2	Deaths involving Pneumonia, with or without COVID-19, excluding Influenza deaths (J12.0–J18.9)3	Deaths involving COVID-19 and Pneumonia, excluding Influenza (U07.1 and J12.0–J18.9)3	All Deaths involving Influenza, with or without COVID-19 or Pneumonia (J09–J11), includes COVID-19 or Pneumonia4	Deaths involving Pneumonia, Influenza, or COVID-19 (U07.1 or J09–J18.9)5
Total Deaths	140,571	1,576,925	108	148,732	61,132	6,589	233,790
2/1/2020	0	58,456	99	3,785	0	479	4,264
2/8/2020	1	59,206	99	3,789	0	520	4,310
2/15/2020	0	58,522	99	3,812	0	555	4,367
2/22/2020	5	58,597	101	3,680	1	563	4,247
2/29/2020	7	58,941	103	3,806	4	651	4,460
3/7/2020	35	59,104	102	3,931	17	628	4,576
3/14/2020	52	57,894	101	3,918	27	612	4,554
3/21/2020	565	58,643	103	4,510	251	551	5,368
3/28/2020	3,147	62,641	112	6,149	1,423	440	8,263
4/4/2020	9,946	71,881	129	9,866	4,728	477	15,325
4/11/2020	16,090	78,642	142	11,932	7,193	472	20,961
4/18/2020	16,987	76,313	141	11,348	7,281	265	21,130
4/25/2020	15,333	73,329	136	10,310	6,571	143	19,119
5/2/2020	13,046	68,716	128	8,884	5,482	65	16,493
5/9/2020	11,059	66,208	126	7,759	4,668	47	14,187
5/16/2020	9,060	63,810	122	6,670	3,733	20	12,014
5/23/2020	7,072	60,842	117	5,794	2,935	23	9,950
5/30/2020	6,030	58,736	113	5,171	2,442	11	8,770
6/6/2020	4,899	57,641	110	4,785	2,103	11	7,592
6/13/2020	4,103	56,261	109	4,398	1,828	11	6,681
6/20/2020	3,676	55,336	107	4,175	1,554	6	6,303
6/27/2020	3,553	54,340	106	3,945	1,461	10	6,046
7/4/2020	4,005	53,842	104	4,061	1,772	4	6,295
7/11/2020	4,629	53,489	104	4,625	2,197	7	7,064
7/18/2020	4,608	49,076	96	4,326	2,198	11	6,744
7/25/2020	2,405	35,571	70	2,708	1,130	6	3,986
8/1/2020	258	10,888	21	595	133	1	721

"The Key to Defeating COVID-19 Already Exists. We Need to Start Using It"/ Newsweek/ Harvey Risch, MD, PhD, Yale professor of epidemiology

The following is the text of Professor Harvey Risch's opinion piece in yesterday's issue of Newsweek.

As professor of epidemiology at Yale School of Public Health, I have authored over 300 peer-reviewed publications and currently hold senior positions on the editorial boards of several leading journals. I am usually accustomed to advocating for positions within the mainstream of medicine, so have been flummoxed to find that, in the midst of a crisis, I am fighting for a treatment that the data fully support but which, for reasons having nothing to do with a correct understanding of the science, has been pushed to the sidelines. As a result, tens of thousands of patients with COVID-19 are dying unnecessarily. Fortunately, the situation can be reversed easily and quickly.

I am referring, of course, to the medication hydroxychloroquine. When this inexpensive oral medication is given very early in the course of illness, before the virus has had time to multiply beyond control, it has shown to be highly effective, especially when given in combination with the antibiotics azithromycin or doxycycline and the nutritional supplement zinc.

On May 27, I published an article in the American Journal of Epidemiology (AJE) entitled, "Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis." That article, published in the world's leading epidemiology journal, analyzed five studies, demonstrating clear-cut and significant benefits to treated patients, plus other very large studies that showed the medication safety.

Physicians who have been using these medications in the face of widespread skepticism have been truly heroic. They have done what the science shows is best for their patients, often at great personal risk. I myself know of two doctors who have saved the lives of hundreds of patients with these medications, but are now fighting state medical boards to save their licenses and reputations. The cases against them are completely without scientific merit.Since publication of my May 27 article, seven more studies have demonstrated similar benefit. In a lengthy follow-up letter, also published by AJE, I discuss these seven studies and renew my call for the immediate early use of hydroxychloroquine in high-risk patients. These seven studies include: an additional 400 high-risk patients treated by Dr. Vladimir Zelenko, with zero deaths; four studies totaling almost 500 high-risk patients treated in nursing homes and clinics across the U.S., with no deaths; a controlled trial of more than 700 high-risk patients in Brazil, with significantly reduced risk of hospitalization and two deaths among 334 patients treated with hydroxychloroquine; and another study of 398 matched patients in France, also with significantly reduced hospitalization risk. Since my letter was published, even more doctors have reported to me their completely successful use.

My original article in the AJE is available free online, and I encourage readers—especially physicians, nurses, physician assistants and associates, and respiratory therapists—to search the title and read it. My follow-up letter is linked there to the original paper.

Beyond these studies of individual patients, we have seen what happens in large populations when these drugs are used. These have been "natural experiments." In the northern Brazil state of Pará, COVID-19 deaths were increasing exponentially. On April 6, the public hospital network purchased 75,000 doses of azithromycin and 90,000 doses of hydroxychloroquine. Over the next few weeks, authorities began distributing these medications to infected individuals. Even though new cases continued to occur, on May 22 the death rate started to plummet and is now about one-eighth what it was at the peak.

A reverse natural experiment happened in Switzerland. On May 27, the Swiss national government banned outpatient use of hydroxychloroquine for COVID-19. Around June 10, COVID-19 deaths increased four-fold and remained elevated. On June 11, the Swiss government revoked the ban, and on June 23 the death rate reverted to what it had been beforehand. People who die from COVID-19 live about three to five weeks from the start of symptoms, which makes the evidence of a causal relation in these experiments strong. Both episodes suggest that a combination of hydroxychloroquine and its companion medications reduces mortality and should be immediately adopted as the new standard of care in high-risk patients.

Why has hydroxychloroquine been disregarded?

First, as all know, the medication has become highly politicized. For many, it is viewed as a marker of political identity, on both sides of the political spectrum. Nobody needs me to remind them that this is not how medicine should proceed. We must judge this medication strictly on the science. When doctors graduate from medical school, they formally promise to make the health and life of the patient their first consideration, without biases of race, religion, nationality, social standing—or political affiliation. Lives must come first.

Second, the drug has not been used properly in many studies. Hydroxychloroquine has shown major success when used early in high-risk people but, as one would expect for an antiviral, much less success when used late in the disease course. Even so, it has demonstrated significant benefit in large hospital studies in Michigan and New York City when started within the first 24 to 48 hours after admission.

In fact, as inexpensive, oral and widely available medications, and a nutritional supplement, the combination of hydroxychloroquine, azithromycin or doxycycline, and zinc are well-suited for early treatment in the outpatient setting. The combination should be prescribed in high-risk patients immediately upon clinical suspicion of COVID-19 disease, without waiting for results of testing. Delays in waiting before starting the medications can reduce their efficacy.

Third, concerns have been raised by the FDA and others about risks of cardiac arrhythmia, especially when hydroxychloroquine is given in combination with azithromycin. The FDA based its comments on data in its FDA Adverse Event Reporting System. This reporting system captured up to a thousand cases of arrhythmias attributed to hydroxychloroquine use. In fact, the number is likely higher than that, since the reporting system, which requires physicians or patients to initiate contact with the FDA, appreciably undercounts drug side effects.

But what the FDA did not announce is that these adverse events were generated from tens of millions of patient uses of hydroxychloroquine for long periods of time, often for the chronic treatment of lupus or rheumatoid arthritis. Even if the true rates of arrhythmia are ten-fold higher than those reported, the harms would be minuscule compared to the mortality occurring right now in inadequately treated high-risk COVID-19 patients. This fact is proven by an Oxford University study of more than 320,000 older patients taking both hydroxychloroquine and azithromycin, who had arrhythmia excess death rates of less than 9/100,000 users, as I discuss in my May 27 paper cited above. A new paper in the American Journal of Medicine by established cardiologists around the world fully agrees with this.

In the future, I believe this misbegotten episode regarding hydroxychloroquine will be studied by sociologists of medicine as a classic example of how extra-scientific factors overrode clear-cut medical evidence. But for now, reality demands a clear, scientific eye on the evidence and where it points. For the sake of high-risk patients, for the sake of our parents and grandparents, for the sake of the unemployed, for our economy and for our polity, especially those disproportionally affected, we must start treating immediately.

Fauci says "far too many people will die" shortly after cancelling NIAID trial of hydroxychloroquine in early disease

Writing in the New England Journal, Dr. Fauci and his deputy, Clifford Lane tell us that despite "appropriate treatment with Remdesivir and dexamethasone, far too many people with Covid-19 will die."  And if Fauci keeps preventing the use of cheap, available and effective treatments, he will be correct. See "The Key to Defeating COVID-19 Already Exists. We Need to Start Using It" in yesterday's Newsweek, by Harvey Risch, MD, PhD and Professor of Epidemiology at Yale, who does not want "far too many people" to die unnecessarily.

1.  The Fauci article implies that so many people dying is partly the fault of observational studies and anecdotal evidence... whereas large prospective clinical trials can provide the answers we need. The authors list a variety of new drugs (all would be expensive) that hold promise for Covid and need to be tested. Fauci took the same approach to HIV treatment, preventing access to known effective drugs for years.  He has not had much luck finding an HIV vaccine, despite spending a king's ransom in taxpayer dollars looking for one. Yet he promises to produce a Covid vaccine at warp speed.  Who is he kidding?

2.  While congratulating the Recovery trial for its results, which allegedly prove that hydroxychloroquine does not work for Covid-19, the authors emphasize the importance of ethically conducted research, never mentioning the overdosing that characterized Recovery's hydroxychloroquine arm, and no doubt contributed to the 396 deaths in that arm. 

3.  Nor do the authors mention that even the Recovery trial's principal investigators only claim that their trial showed hydroxychloroquine did not work in hospitalized patients. Its benefit in early Covid-19 disease, and its value as a preventive for Covid-19 have yet to be proven in western clinical trials.  India says its 3 clinical trials showed the drug worked, and it is now recommended prophylactically for all medical practitioners and first responders in India who may be exposed.

4.  So why did Capos Fauci and Lane halt the long-promised NIAID trial of hydroxychloroquine in outpatients with early Covid-19 disease after enrolling only 20 subjects, a mere 1% of the 2,000 intended, according to the trial's registration materials on Clinicaltrials.gov?  Were they afraid that given the intense scrutiny this subject is now receiving, they would be unable to 'fix' the results of their very own prospective, randomized, controlled clinical trial?  Frightened it would reveal more evidence that hydroxychloroquine actually works well against SARS-CoV-2?

Excerpts from Fauci/Lane's NEJM opinion piece, with my comments in parentheses:

In the RECOVERY trial, the benefit of the glucocorticoid dexamethasone for patients with Covid-19 who were receiving mechanical ventilation at the time of randomization was clearly shown. A 28-day mortality of 29.3% was reported for patients in the dexamethasone group as compared with 41.4% in the usual care (i.e., nothing curative used--Nass) group. In contrast, no benefit for dexamethasone was seen in patients not requiring oxygen at the time of randomization, with 28-day mortality of 17.8% and 14.0% for the dexamethasone group and the usual care group, respectively. For the heterogeneous group of patients receiving oxygen without invasive mechanical ventilation, mortality was 23.3% in the dexamethasone group and 26.2% in the usual care group.

(The MATH+ protocol recommended steroids for late Covid-19 patients back in April.  The patients treated with this protocol received other drugs as well, and reportedly have had much lower mortality rates, but so far the results have not been published.  Mortality rates in the Recovery trial are among the highest reported in the world.--Nass)

These findings, while limited to patients with Covid-19, provides clarity to an area of therapeutic controversy and probably will result in many lives saved. (sic) The use of dexamethasone already has been endorsed by several treatment-guideline panels, including that convened by the U.S. National Institutes of Health. 

(This is the guidelines group put together by coauthor Clifford Lane, who has financial COIs with Gilead, and who placed 15 others with Gilead connections on the guidelines committee, which included himself.--Nass)

The key to the success of the RECOVERY trial has been its pace of enrollment. The ability to rapidly enroll thousands of patients into the trial no doubt was facilitated by the National Health Service in the United Kingdom and the fact that the trial was available to essentially the entire patient population of the country. 

(While the authors crow about the "availability" to patients of being a subject in the Recovery clinical trial, I would posit that being in the trial led to less individualized treatment, use of fewer therapeutic agents, and higher mortality rates.--Nass) 

As noted by the authors, 15% of all the patients who were hospitalized with Covid-19 in the United Kingdom were enrolled in the trial. 

Despite the decreases in death and complications that are likely to result from appropriate treatment of patients with remdesivir and dexamethasone, far too many people with Covid-19 will die.

Scientifically robust and ethically sound clinical research remains the quickest and most efficient pathway to effective treatment and prevention strategies for patients with Covid-19. It is our responsibility in the global medical research community to rapidly design, implement, and complete studies of the most promising therapeutic agents and vaccines against this disease. These agents include monoclonal antibodies, more selective immunosuppressive agents, and vaccines built on platforms ranging from nucleic acids to proteins to recombinant viruses. 

(But if Fauci is to get the opportunity to trial those novel, expensive drugs and vaccines, some of which have yet to be invented, he would need to keep the pandemic going. Which is certainly not ethically sound, nor is it quick and efficient.--Nass)

Masking Lack of Evidence/ Oxford's Center for Evidence-Based Medicine

Curious about the scientific evidence regarding masking?  It turns out, according to two Oxford professors of Evidence-Based Medicine who reviewed the world literature on this subject, that no reliable scientific evidence supports the use of masks.  No reliable evidence says they don't work, either.  The "science" does not help us understand their pros and cons.  

So why demand them?  Perhaps because the authorities have to DO something?   Anthrax vaccine was required for soldiers, apparently because it immunized commanders against the accusation that they did not do 'everything possible' to protect their troops.  Mask requirements perhaps immunize authorities in the same way.

You can look at the evidence on masks a the Center for Evidence-Based Medicine website.  Or you can listen to an amazing, illuminating discussion by the two professors on masks, lockdowns, data, and disastrous decisions that were made regarding the pandemic.  I cannot recommend it enough.

Compilation of over 50 studies of Hydroxychloroquine in Covid-19 (+/- zinc, azithro, etc.) @ https://c19study.com/

This entire post is a copy of the website in the title.  I was in a hurry when I posted it and did not make that clear. 
https://c19study.com/

@CovidAnalysis

 

 

Share

 

Tweet

PrEP
100%

 

PEP
100%

 

Early
100%

 

Late
61%

 

All
75%

 

  65 studies (39 peer reviewed)
  COVID deaths: 

660,803

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

7/26	Inconc.	PEP	Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint)	A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease
		Death rate reduced from 0.6% to 0.4%, RR 0.71, 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, vs. ove..
7/24	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 HCQ 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..
7/23	Negative	Late	Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed)	Hydroxychloroquine 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..
7/21	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
		HCQ 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 ..
7/20	Meta (positive)	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.
7/18	Meta (positive)	PEP	Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in the study count)	Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19
		Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early, p<0 .01.="" considering="" effectiveness="" especially="" found="" is="" limitatio..="" notable="" td="" the="">
7/16	Inconc.	Early	Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed)	Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
		~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ reduced combined hospitalization/death by 50%, p=0.29 (5 HCQ cases, 10 control cases), and reduced hospitalization by 60%,..
7/16	Inconc.	Early	Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed)	Hydroxychloroquine 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..
7/9	Meta (positive)	Early, Late	Raoult et al., Preprint (Preprint) (meta analysis - not included in the study count)	Hydroxychloroquine 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.
7/7	Negative	Late	An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint)	Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
		Retrospective of hospitalized patients with 31 HCQ 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. ..
7/3	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 HCQ 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	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 Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
		Early treatment with HCQ+AZ+Z results in 84% lower hospitalization and 80% lower death - hospitalization OR 0.16 (p<0 .001="" 0.2="" 37..="" 518="" cardiac="" death="" effects.="" no="" or="" p="0.16)." patients="" retrospective="" side="" td="" treated="">
7/1	Positive	Late	Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed)	Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
		HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospecti..
7/1	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..
6/30	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
		HCQ 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.
6/29	Positive	PrEP	Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed)	Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection
		Chronic treatment with HCQ 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	Safety	N/A	Mfeukeu-Kuate et al. (Preprint) (not included in the study count)	Electrocardiographic safety of daily Hydroxychloroquine 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 HCQ+AZ. 51 relatively young patients 39 +/- 11.
6/25	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 hydroxychloroquine/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.
6/22	In Vitro	In Vitro	Wang et al., bioRxiv, doi:10.1101/2020.06.22.164665 (Preprint) (In Vitro) (not included in the study count)	Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus
		In vitro study, not included in the study count or percentages. CQ and HCQ inhibit the entry of COVID-19 spike pseudotype virus using ACE2 high expressed HEK293T cells.
6/22	Positive	Early	Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint)	Efficacy and safety of chloroquine or hydroxychloroquine 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 (HCQ), p=0.01. 67 patients with mild/moderate cases.
6/19	Positive (news)	PrEP	SMSH Sawai Man Singh Hospital, India (News) (not included in the study count)	HCQ 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	Negative (news)	Late	NIH, study not available yet (News) (not included in the study count)	NIH halts clinical trial of hydroxychloroquine
		NIH halts late stage trial reporting no harm and no benefit. 470 patients.
6/19	Positive	Late	Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint)	Hydroxychloroquine 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 HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control ..
6/18	Inconc.	Late	Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed)	Compassionate use of hydroxychloroquine 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.
6/17	Positive	Late	Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed)	Hydroxychloroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China
		30 hospitalized patients. Early use of HCQ is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization.
6/17	Negative (news)	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 HCQ 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..
6/16	Positive (news)	PrEP	WHIP COVID-19 (News) (not included in the study count)	Henry Ford Health System still moving forward with hydroxychloroquine study
		Ongoing WHIP COVID-19 HCQ PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HCQ. For more details on the study se..
6/12	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 Hydroxychloroquine-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 HCQ+AZ.
6/12	Negative	Late	Giacomelli et al., medRxiv, doi:10.1101/2020.06.05.20123299 (Preprint)	Early administration of lopinavir/ritonavir plus hydroxychloroquine 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..
6/10	Positive	Early	Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint)	A short therapeutic regimen based on hydroxychloroquine 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, HCQ+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy.
6/9	Positive	Late	Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed)	Beneficial effect of Hydroxychloroquine-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, HCQ+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	PrEP	Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint)	Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers
		HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
6/6	Meta (positive)	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 Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
		[H]CQ effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
6/5	Negative	Late	Horby et al., medRxiv, 7/15/2020, doi:10.1101/2020.07.15.20151852 (press release 6/5) (Preprint)	Effect of Hydroxychloroquine 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..
6/3	Positive (see notes)	PEP	Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed)	A Randomized Trial of Hydroxychloroquine 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..
5/31	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 Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
		Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0 .0001="" class="hs" span="" style="display: inline-block; margin: 0px; max-width: 0.01em; padding: 0px; width: 0.01em;">

Q+AZ) or 13 days, p<0 .0001="" 88="" analysis="" cardiac="" case="" control="" matched="" no="" of="" pa..="" patients="" retrospective="" small="" study="" td="" toxicity.="" with="">

5/29

Positive

LateAyerbe 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. HCQ reduces mortality from 30% to 13%. Not adjusted for age and gender. HCQ group 10% more males and 6 years younger. Study primarily interested in Heparin.

5/28

Positive

LateChamieh 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 hydroxychloroquine and azithromycin in Lebanon HCQ+AZ potentially explains 94.7% success in treating a fairly complex cohort.

5/28

Positive

PrEPChatterjee 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 HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists.

5/28

Positive

LateHuang 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 chloroquine for the treatment of COVID-19 197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.

5/27

Meta

EarlyRisch, 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.

5/25

Negative

LateIp et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint)Hydroxychloroquine 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 HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]..

5/22

Positive
(advisory)

PEP, PrEPICMR, Indian Council of Medical Research (Advisory) (not included in the study count)Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection Healthcare workers on HCQ prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HCQ prophylaxis to asymptomatic household contacts of cases and fron..

5/22

Retracted

LateMehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed)Hydroxychloroquine or chloroquine 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.

5/20

Meta
(negative)

LateChacko et al., medRxiv, doi:10.1101/2020.05.14.20101774 (Preprint) (meta analysis - not included in the study count)Hydroxychloroquine 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..

5/19

Negative

LateSingh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint)Outcomes of Hydroxychloroquine 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..

5/18

Positive

LateKim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint)Treatment Response to Hydroxychloroquine, 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 HCQ+antibiotic. Preprint withdrawn pending peer review.

5/18

Positive

EarlyAhmad et al., doi:10.1101/2020.05.18.20066902 (Preprint)Doxycycline and Hydroxychloroquine 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 HCQ+AZ compared to 22% using a naive indirect comparison.

5/16

Inconc.

PrEPMacias 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 hydroxychloroquine therapy Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HC

5/15

Positive

LateYu et al., Sci China Life Sci., 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed)Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19 Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ.

5/14

Negative

LateMahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed)Clinical efficacy of hydroxychloroquine 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 HCQ. Power of study appears too low to support conclusions [1]. None of the 15 patients receiving HC<..

5/11

Positive

LateDavido et al., medRxiv, doi:10.1101/2020.05.05.2008875 (Preprint)Hydroxychloroquine plus azithromycin: a potential interest in reducing in hospital morbidity due to COVID-19 pneumonia (HI-ZY-COVID)? Retrospective of 132 hospitalized patients. HCQ+AZ significantly reduces death. Note that due to the controversy, authors withdrew this paper from medRxiv pending peer review.

5/11

Negative

LateRosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed)Association of Treatment With Hydroxychloroquine 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.

5/10

Positive

LateAlberici 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 HCQ but p=0.12, OR 0.44 (0.16–1.24).

5/8

Positive

LateCarlucci et al., doi:10.1101/2020.05.02.20080036 (Preprint)Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients Observational retrospective. Addition of Zinc to HCQ+AZ reduces mortality.

5/7

Theory

TheoryDerendorf, 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 hydroxychloroquine and azithromycin Discusses pharmacokinetic properties of HCQ+AZ as a potential underlying mechanism of the observed antiviral effects.

5/7

Inconc.

LateGeleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed)Observational Study of Hydroxychloroquine 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

Positive
(news)

N/ASermo (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 HCQ used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians.

5/6

Animal

AnimalMaisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count)Hydroxychloroquine use against SARSCoV-2 infection in non-human primates Monkey study which reports no effect of HCQ or HCQ+AZ. However, there are actually several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and contr..

5/5

Positive

LateMembrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint)Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study 166 patients hospitalised with COVID-19, HCQ 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

Early, LateMillion 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 Hydroxychloroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France Retrospective 1061 patients. HCQ+AZ safe and results in a low fatality rate.

5/5

Inconc.

PrEPGendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed)Continuous Hydroxychloroquine 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 HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases..

5/1

Safety

N/AMercuro 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 Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19) Study of 90 hospitalized patients given HCQ, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HCQ, and 442ms for HCQ+AZ. Medi..

5/1

Safety

N/ABessière 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 Hydroxychloroquine 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. HCQ with or w/o AZ was given to 4..

5/2

Positive
(news)

LateSeydi (News) (not included in the study count)Coronavirus: a study in Senegal confirms the effectiveness of hydroxychloroquine Preliminary results of Senegal trial with 181 patients showing faster recovery with HCQ, and even faster recovery with HCQ+AZ.

4/30

Positive

EarlyMeo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed)Efficacy of chloroquine and hydroxychloroquine 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 CQ/HCQ (widely used for malaria) are pr..

4/29

Safety

N/ASaleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed)The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection 201 hospitalized patients. No serious side effects of HCQ. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, c..

4/25

In Vitro

In VitroAndreani 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 hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect HCQ and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.

4/24

Positive

EarlyAshraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint)COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes 100 patients. HCQ improved clinical outcome.

4/21

Positive

EarlyIzoulet 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]CQ, showing dramatically lower death in [H]CQ countries. This paper does not at..

4/21

Negative

LateMagagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed)Outcomes of hydroxychloroquine 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 HCQ or HCQ+AZ. Study notes HCQ was more likely..

4/17

Positive

PEPLee 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.

4/16

Negative

LateBorba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed)Chloroquine 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..

4/15

Positive

EarlyEsper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint)Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine 636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.

4/14

Negative

LateTang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed)Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial 150 patients very late stage RCT. No significant difference. More symptomatic relief with HCQ. No safety concerns of HCQ. Treatment very late, average 16.6 days after symptom onset. Data favor..

4/13

Positive

LateGao 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 Chloroquine/Hydroxychloroquine to Treat Coronavirus Disease 2019 (COVID-19) Increasing evidence from completed clinical studies shows CQ and HCQ effective (HCQ more effective).

4/12

Negative

LateBarbosa et al., Preprint (Preprint)Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19 : a quasi-randomized comparative study Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been publishe..

4/11

Positive

EarlyGautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed)Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study Pilot study suggesting improvement with HCQ+AZ and recommending further study.

4/10

Meta
(negative)

LateLover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in the study count)Quantifying treatment effects of hydroxychloroquine 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 HCQ treatment, with more significant effects from [HCQ+AZ]".

4/1

Positive

LateHuang 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 Chloroquine 22 patients. All CQ patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for CQ vs. 6.5 days for Lopinavir/Rotinavir.

3/31

Positive

LateChen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint)Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial 62 patients. RCT showing significantly faster recovery with HCQ. 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

In Vitro

In VitroClementi 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 Hydroxychloroquine 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.

3/28

Negative
(letter)

LateMolina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter to the editor)No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection 11 patients with severe cases. No evidence of benefit for HCQ.

3/26

Positive
(news)

LateZhong Nanshan (钟南山) (News) (not included in the study count)Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial 197 patients. HCQ effective. Viral RNA negative in 95.9% versus 79.6% control. Median time to negative tests 3 days versus 9 days for control.

3/24

Theory

TheoryPagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory)Is Hydroxychloroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19? CQ and HCQ 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 ..

3/23

Theory

TheoryHu 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 chloroquine efficacy against COVID-19 CQ is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.

3/21

Positive
(advisory)

PrEPICMR, Indian Council of Medical Research (Advisory) (not included in the study count)Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection Recommends HCQ for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo.

3/20

Positive
(news)

LateHu 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 HCQ with 184 cases and 21 hospitals show HCQ is effective.

3/18

In Vitro

In VitroLiu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count)Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro HCQ effective in vitro and less toxic than CQ. In addition to direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensiv..

3/17

Positive

EarlyGautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed)Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial HCQ significantly associated with viral load reduction / elimination, enhanced with AZ.

3/17

Review

N/ASahraei 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): chloroquine or hydroxychloroquine Discussion of mechanisms of action, CQ vs. HCQ, early studies, safety.

3/13

Review

N/ATodaro 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 CQ and HCQ, recommending use.

3/12

Theory

TheoryDevaux 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 chloroquine against coronavirus: what to expect for COVID-19? Discusses mechanisms of CQ interference with the SARS-CoV-2 replication cycle.

3/10

Meta
(positive)

N/ACortegiani 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 Chloroquine 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.

3/9

In Vitro

N/AYao 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 Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) HCQ is more potent than CQ in vitro for inhibiting SARS-CoV-2. Simulates HCQ concentration in lung fluid and provides dosing recommendations.

3/6

Negative

LateChen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed)A pilot study of hydroxychloroquine 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 HCQ but not statistically significant. One HCQ patient developed to ..

3/4

Positive

LateColson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Peer Reviewed)Chloroquine and Hydroxychloroquine as Available Weapons to Fight COVID-19 Recommending CQ and HCQ for COVID-19 based on 20 clinical studies in China and a strong rationale for use.

2/20

Positive

LateJiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed)Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia Early trials in China show CQ results in shorter hospital stays and improved patient outcomes.

2/19

Positive

LateGao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed)Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies Results from 15 clinical trials in China showing CQ is effective.

2/17

Positive
(news)

LateSun 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 HCQ under clinical trials in >10 hospitals in China and has shown fairly good efficacy.

2/4

In Vitro

In VitroWang 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 chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro In vitro study, not included in the study count or percentages. Remdesivir and CQ potently blocked virus infection in vitro.

2014

In Vitro

In Vitrode 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 CQ inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range.

2012

Animal

AnimalYan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count)Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model CQ, 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.

2009

Animal

AnimalKeyaerts 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 Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice CQ inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with CQ acquired transplacentally or via maternal milk. The highest survi..

2008

In Vitro

In VitroKono 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 chloroquine: Involvement of p38 MAPK and ERK CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracell..

2006

In Vitro

In VitroSavarino 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 chloroquine Update to 2003 paper, not included in the study count or percentages. Hypothesis of CQ inhibiting SARS replication has been confirmed in two in-vitro studies. CQ affected an early stage of SAR..

2005

In Vitro

In VitroVincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count)Chloroquine is a potent inhibitor of SARS coronavirus infection and spread In vitro study, SARS-CoV-1, not included in the study count or percentages. CQ has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treat..

2004

In Vitro

In VitroKeyaerts 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 chloroquine In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of CQ for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inh..

2003

Theory

TheorySavarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count)Effects of chloroquine on viral infections: an old drug against today's diseases Not included in the study count or percentages. Discussion/review noting that CQ exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coron..

1896

Inconc.
(news)

N/AEdwin Wiley Grove (News) (not included in the study count)Laxative Bromo Quinine Quinine has been used for respiratory infections since 1896. Not included in the study count or percentages, just as an interesting observation.

Note: In Vitro, Meta, Theory, Safety, Review, and News items are not included in the percentages and study count. There is a total of 110 items. Positive/negative effects vary in degree and certainty, please read the papers or descriptions thereof for more details.

Please send us corrections, updates, comments. Please send us any missing papers but check first - almost all submissions to date were already posted.