Dr. Daniel Cameron: Inside Lyme Podcast
COVID-19 Podcast: Hydroxychloroquine and azithromycin for COVID-19 may be effective after all.
Welcome to my next Inside Lyme podcast. – I will examine the evidence supporting hydroxychloroquine and azithromycin for COVID-19.
You may be wondering why I am discussing COVID-19 during an Inside Lyme podcast. I am concerned for my children, grandchildren, and my patients. I want to share my understanding of COVID-19 through my eyes as a clinical epidemiologist.
COVID-19 is now a pandemic. We need an effective and safe drug to treat this virus.
Researchers have turned to existing drugs that might be effective without causing significant side effects. Hydroxychloroquine and chloroquine have been prescribed for the treatment and prophylaxis of malaria in addition to the treatment of autoimmune diseases. Hydroxychloroquine and azithromycin have also been prescribed for Lyme disease patients. Hydroxychloroquine and azithromycin have been marketed under the name Plaquenil and Zithromax, respectively in the US.
Both chloroquine and hydroxychloroquine have side effects. The most common side effect of hydroxychloroquine is nausea and diarrhea. In rare cases, hydroxychloroquine can lead to reduced white blood cells, platelets count, anemia, and retinopathy. Retinopathy can lead to color blindness and loss of vision. Both hydroxychloroquine and azithromycin can lead to sudden death from a prolonged QT interval.
Antiviral effects of Hydroxychloroquine and chloroquine
Hydroxychloroquine and chloroquine have shown some antiviral benefits in vitro (Wang, 2020, letter) Both have been studied for other related viruses, including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (Mers).
Chloroquine improved outcomes in a series of small studies in China. Gao and colleagues discussed the finding in the journal BioScience Trends . “Thus far, results from more than 100 patients have demonstrated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion, and shortening the disease course according to the news briefing.” These findings led the State Council in China to approve chloroquine for COVIID-19Hydroxychloroquine and azithromycin for COVID-19 may be effective after all. Click To Tweet
Unfortunately, this series of Chinese trials do not appear to have been published. It is hard to discuss these Chinese trials until they are published.
First French clinical trial by Gautret and colleagues
Gautret and colleagues published a French trial evaluating the benefit and risks of hydroxychloroquine and Zithromax for the treatment of COVID-19.
The authors prescribed 600 mg of hydroxychloroquine to 26 patients with COVID-19. Two were asymptomatic. Ten had upper tract respiratory infections, and six had lower tract respiratory infections. The doctors prescribed azithromycin to 6 of their patients with COVID-19 to prevent bacterial superinfection.
The authors were able to show a significant reduction in the viral load in nasopharyngeal samples of their COID-19 patients treated with hydroxychloroquine compared to COVID-19 patients who were not treated.
The authors were able to show even a greater reduction in viral load in the six COVID-19 patients when Zithromax was added.
Only one of the 26 patients treated with hydroxychloroquine was dropped from the study due to an adverse event. That patient dropped out due to nausea.
The authors explained why they decided to share their findings early. “For ethical reasons and because our first results are so significant and evident, we decide to share our findings with the medical community, given the urgent need for an effective drug against SARS-CoV-2 in the current pandemic context.”
Flaws in the first French trial by Gautret
The Gautret trial was small and flawed. They should have used controls from the same hospital with the same characteristics as the 26 treated patients. Instead, they enrolled 16 controls were from other centers.
The Gautret trial did not evaluate whether a reduction or elimination of the COVID-19 virus in saliva would prevent outcomes important to patients such as a transfer to an intensive care unit or death. Four of the 26 patients treated with hydroxychloroquine did poorly. Three were transferred to the intensive care unit. One died. None of the patients with a COVID—19 infection developed a QT prolongation.
The Gautret trial was not designed to determine if the absence if COVID-19 from the saliva meant the absence of COVID-19 from other tissues.
The Gautret trial could not determine if the benefits seen for the six COVID-19 patients treated with azithromycin were from an antiviral effect or an antibiotic effect.
Second French trial
A recently published second French trial by Gautret and colleagues added further support for the hydroxychloroquine with azithromycin. “In 80 in-patients receiving a combination of hydroxychloroquine and azithromycin we noted a clinical improvement in all but one 86 year-old patient who died, and one 74-year-old patient still in intensive care unit.”
Researchers at the University of Minnesota are planning on a trial “to see whether malaria treatment hydroxychloroquine can prevent or reduce the severity of the coronavirus disease (COVID-19)” writes Gabe Gutierrez and Dennis Romero in NBCNews.
Could cutting the COVID-19 viral load be helpful?
Yes, according to Gautret. “hydroxychloroquine and azithromycin “can play a role in controlling the disease epidemic by limiting the duration of virus shedding, which can last for several weeks in the absence of specific treatment.” write Gautret.
Could hydroxychloroquine and azithromycin for individuals with COVID-19 be helpful?
Yes, according to both Gautret trials. Hydroxychloroquine and azithromycin lowered the COVID-19 viral load patient. Moreover, most of the patients with a COVID-19 infection were improved or discharged in the second Gautret trial.
Could hydroxychloroquine and azithromycin prevent COVID-19 infection?
Neither Gautret trials assessed whether hydroxychloroquine with azithromycin would be effective for prophylaxis before an infection. The study only enrolled hospitalized patients already infected with the COVID-19 virus.
For now, researchers and politicians are divided on whether to recommend hydroxychloroquine and azithromycin for the prevention and treatment of COVID-19. There is growing pressure on doctors to wait for science.
Doctors have patients who are sick now. Doctors have patients who want to prevent getting COVID-19.
“The Food and Drug Administration (FDA) on Sunday issued an emergency-use authorization for a pair of anti-malaria drugs as health officials work to combat the rapid spread of the novel coronavirus.” writes Jusin Wise in The Hill.
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- Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
- Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949.
- Cai J, Xu J, Lin D, Yang Z, Xu L, Qu Z, Zhang Y, Zhang H, Jia R, Liu P, Wang X, Ge Y, Xia A, Tian H, Chang H, Wang C, Li J, Wang J, Zeng M. A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis. 2020 Feb 28. pii: ciaa198
- Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73.
- Gautret P, Lagier JC, Parola P, and colleagues. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study. To be published as of 3/20/20.
- Clinical trials on coronavirus drugs may take only months, researcher says. Gabe Gutierrez and Dennis Romero, From NBCNew.com Last accessed 3/29/20.