A compilation of evidence on hydroxychloroquine and azithromycin in treatment of COVID-19 and breaking results from antibody prevalence studies
Please visit https://www.medicineuncensored.com for BREAKING results from the latest antibody studies and HCQ trials in treatment of COVID-19.
ALL UPDATES WILL BE POSTED AT https://www.medicineuncensored.com FROM NOW ON.
By James M. Todaro, MD
Twitter: @JamesTodaroMD
covidtrial.io
Table of Contents
Recent publications by James Todaro, MD on COVID-19
COVID-19 antibody prevalence results and new estimates of infection fatality rates
Evidence on hydroxychloroquine, azithromycin and zinc in early treatment of COVID-19
Upcoming clinical trials on efficacy of HCQ in prevention of COVID-19
Antiviral properties of azithromycin
Cardiac injury and myocarditis in COVID-19
Safety profile of hydroxychloroquine and azithromycin
Antiviral effects of zinc supplements and synergy with chloroquine
Efficacy of chloroquine against SARS-CoV-1
Given the nature of this rapidly spreading pandemic, some of this evidence is anecdotal or expert opinion.
This is not medical advice and is for informational purposes only. Any mention of dosages is for informational purposes only and not for medical use. Please consult a medical professional.
The list is organized such that the newest evidence is continually added to the top of the list.
Recent publications by James Todaro, MD on COVID-19
* An Effective Treatment for Coronavirus (COVID-19) by James M. Todaro, MD and Gregory J. Rigano, Esq. March 13, 2020.
* A two-step strategy to reopen America by James M. Todaro, MD, Joey Krug, Moshe E. Praver, MD and Vladimir Zelenko, MD. April 23, 2020.
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COVID-19 antibody prevalence results and new estimates of infection fatality rates
* Miami antibody study in a sample of nearly 1,800 people in mid-April showed a population prevalence of COVID-19 between 4.4% and 7.9%, projecting an estimated 165,000 adults already infected in Miami-Dade County. This is a 17-fold higher prevalence than confirmed cases in the area at the time, and has a projected infection fatality rate of 0.2%.
* New York antibody study in a sample of 3,000 people in mid-April showed a population prevalence of COVID-19 to be ~21% in NYC, projecting an estimated 1.8 million already infected. This is approximately a 15-fold higher prevalence than confirmed cases in the area at the time. Based on these estimates, the infection fatality rate of novel-coronavirus is ~0.5%. Source: Governor Andrew Cuomo, daily news briefing, April 23, 2020.
* USC antibody study in LA County in a sample of nearly 1,000 people in early April showed a population prevalence of COVID-19 between 2.8% and 5.6%, projecting an estimated 221,000-442,000 adults already infected in LA County. This is a 28 to 55-fold higher prevalence than confirmed cases in the area at the time. Based on these estimates, the infection fatality rate of novel-coronavirus is between 0.14% and 0.27%.
* German antibody study near the border of the Netherlands in 500 residents in early April showed a population prevalence of COVID-19 to be ~14% with an estimated infection fatality rate of 0.37%.
* Stanford antibody study in Santa Clara County in a sample of 3,330 people in early April showed a population prevalence of COVID-19 between 2.49% and 4.16%, projecting an estimated 48,000-81,000 people already infected in Santa Clara County. This is a 50 to 85-fold higher prevalence than confirmed cases in the area at the time. Based on these estimates, the infection fatality rate (IFR) of novel-coronavirus is between 0.12% and 0.2%.
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Evidence on hydroxychloroquine, azithromycin and zinc in early treatment of COVID-19
* Observational study in Spain of early treatment with hydroxychloroquine in 166 COVID-19 patients showed a significant survival benefit in patients started on hydroxychloroquine in the mild stage of disease. Patients were categorized into one of three groups at initial presentation: mild, moderate or severe. There was a significant survival benefit in the mild group compared to controls (1.8 times, p = 0.032) and a trend toward survival benefit in the moderate and severe groups (1.4 times and 1.6 times, respectively). Of note, the average time between symptom onset and treatment was 7 days.
* Prospective observational study assessing cardiac risk of hydroxychloroquine, chloroquine and azithromycin in treatment of 201 COVID-19 patients resulted in no episodes of Torsade de pointes, no arrhythmogenic deaths and prolonged QT interval requiring discontinuation of therapy in 3.5% of patients. Of note, 59% of patients received azithromycin in combination with hydroxychloroquine or chloroquine.
* Dr. Didier Raoult challenges the results of the VA study on hydroxychloroquine (Magagnoli et al) pointing to flaws that could result in a higher mortality rate in the hydroxychloroquine treatment group. Of note, there was a significant difference in baseline characteristics between the treatment and control arms in this retrospective analysis. The hydroxychloroquine treatment arms had significantly higher proportions of patients with lymphopenia (low levels of lymphocytes--a type of white blood cell), which has been shown previously to correlate with higher mortality risk. Dr. Raoult also points out the severity of illness in the cohort, such that a substantial percent of the patients were likely intubated prior to receiving hydroxychloroquine treatment out of desperation, and resulting in a higher mortality rate.
* In a letter to Arizona Governor Ducey, the Association of American Physicians and Surgeons (AAPS) reported treatment of 2,333 COVID-19 patients in Phoenix with hydroxychloroquine +/- azithromycin and zinc. Of this cohort, 91.6% of patients treated with hydroxychloroquine improved clinically. There were 63 deaths, with the vast majority (52/63) attributed to a single VA report of hydroxychloroquine use in severely ill patients.
* Observational, non-comparative study of 1061 COVID-19 patients treated early with hydroxychloroquine and azithromycin in Marseille resulted in 91.7% virologically cured within 10 days (prior studies report viral shedding duration over 20 days in 50% and 30% of patients, F Zhou et al (The Lancet) and KKW To et al (The Lancet)). Mortality rate in the total cohort was 0.75%, lower than the mortality rates for other treatment regimens in all other Marseille public hospitals (p < 0.01). The mean time between symptom onset and treatment with HCQ+AZ was 6.4 days. To date, this is the largest cohort study published on the efficacy of early treatment with HCQ+AZ.
* Dr. Zelenko reports successfully treating hundreds of COVID-19 positive and suspected patients in New York with a regimen of hydroxychloroquine, azithromycin and zinc with only two deaths as of April 12, 2020—a mortality rate of 0.14%.
* Preliminary results from a study in New York on hydroxychloroquine with or without azithromycin in treatment of COVID-19 show no effect on critically ill patients, announced Governor Andrew Cuomo in a press conference on April 23, 2020. These results are in agreement with other studies below that late treatment with hydroxychloroquine has little to no beneficial effect on patient outcomes.
* Retrospective analysis of 368 hospitalized patients at the VA in Virginia who received hydroxychloroquine, hydroxychloroquine + azithromycin or standard therapy in treatment of COVID-19. Rates of death were 27.8%, 22.1% and 11.4% in the HCQ, HCQ+AZ and standard therapy groups, respectively. The risk of all-cause mortality in the HCQ group was significantly higher than in the standard therapy group. Of note, it is unclear how long from time of symptom onset patients began treatment. However, with mortality rates over 10% in all groups (far higher than the national average among confirmed cases), it is apparent that this was a very sick cohort of patients likely in the advanced stages of illness. This is further evidence that late treatment with HCQ may have minimal or no benefit.
* A non-randomized, prospective study in Sao Paulo, Brazil of 636 symptomatic outpatients treated with hydroxychloroquine for 7 days and azithromycin for 5 days vs control group showed a significant decrease in need for hospitalization. Only 1.9% versus 5.4% of patients in the treatment group needed hospitalization compared to the control group (p < 0.001) with a number needed to treat (NNT) of 28. In a subgroup analysis of outpatients who started treatment within the first 7 days of symptoms, the need for hospitalization decreased to 1.17%. Of note, the treatment group was clinically sicker at baseline than the control group with dyspnea of 22.1% vs 16% (p < 0.0001). Lastly, inclusion criteria was based on flu-like symptoms as opposed to positive COVID-19 testing.
* Randomized controlled trial in China of 150 patients hospitalized for COVID-19 who received either hydroxychloroquine or standard therapy for 2-3 weeks with a primary endpoint of negative conversion rates at 28 days. There was no significant difference in conversion rates between the two arms, but authors did note greater symptomatic relief in patients who received hydroxychloroquine over standard therapy. There were no safety concerns observed in the hydroxychloroquine arm and the most common adverse event was diarrhea (10%). Also of note, treatment was started an average 16.6 days after symptom onset.
* Non-randomized trial of 181 COVID-19 patients hospitalized for hypoxic pneumonia were treated with either 600 mg daily of hydroxychloroquine or standard therapy with primary endpoint of transfer to ICU. Of the patients treated with hydroxychloroquine, 20% also received azithromycin. There was no difference between treatment groups in transfer to ICU or death 7 days after hospital admission.