SGEM Xtra: COVID19 Treatments – Be Skeptical - The Skeptics Guide to Emergency Medicine

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Date: May 9th, 2020

Guest Skeptic: Dr. Sean Moore is an Assistant Professor at the Northern Ontario School of Medicine (NOSM), Chief of Emergency Services at Lake of the Woods Hospital in Kenora, Medical director with Ornge, and Associate Medical Director with CritiCall Ontario.

CAEP Town Hall

We had the pleasure of presenting for the Canadian Association of Emergency Physicians (CAEP) COVID-19 Town Hall this week. CAEP is the national voice of emergency medicine (EM) in Canada and provides continuing medical education, advocates on behalf of emergency physicians and their patients, supports research and strengthens the EM community. In co-operation with other specialties and committees, CAEP also plays a vital role in the development of national standards and clinical guidelines.

Our CAEP COVID-19 Town Hall presentation is available to watch on the CAEP website. It has also been uploaded to CAEP’s YouTube channel. All of the the CAEP COVID-19 Town Halls talks are available free open access. Copies of our slides can be downloaded at this link.

Dr. Sean Moore

Dr. Moore and I were asked to speak about the treatments being used for COVID-19. In this global pandemic, clinicians and researchers have been throwing multiple different treatments at this new corona virus hoping something will work. This includes things like: Azithromycin, Steroids, Famotidine, IL-6 inhibitors, Chloroquine, Hydroxychloroquine, Remdesivir, Vitamin C, and Zinc.

We narrowed our presentation down to five treatments and the evidence behind those treatments. These are listed below with links to the references mentioned in the presentation.

Chloroquine / Hydroxychloroquine

Dr. Didier Raoult

Gautret et al. 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. Travel Med Infect Dis. April 11th, 2020
Tang et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. MedRxIV April 14th, 2020
Chowdhury et al. A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID‐19. AEM May 2020.

We cannot recommend hydroxychloroquine or chloroquine based on the available evidence.

Steroids

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020 Mar 28.
Steroids
Wilson et al. COVID‐19: Interim Guidance on Management Pending Empirical Evidence. From an American Thoracic Society‐led International Task Force. Thoracic April 3rd, 2020
Villar et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Resp Med Feb 7th, 2020
Wu et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Int Med March 13th, 2020

We cannot recommend the use of steroids outside of an RCT. However, steroids should be considered when patients have other indications like COPD or asthma.

Remdesivir

Grein et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. NEJM April 10th, 2020
Wang et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet April 29th, 2020
Fauchi A. Adaptive COVID-19 Treatment Trial (ACTT). Press Conference April 29th, 2020

We cannot recommend the routine use of remdesivir based on the available evidence.

Convalescent Plasma

Convalescent plasma is being investigated but there is very little information on this treatment modality. Currently the CONCOR Trial is underway in Canada using 200-500 ml of plasma. Researchers from across the country are involved including Drs. Donald Arnold, Philippe Begin and Jeannie Callum. Plasma collection was started in April.

We cannot recommend the use of convalescent plasma outside of a research study.

Vaccines

Much work is being done on developing a COVID19 vaccine but that is a least months if not years away. My position on vaccines is that the evidence for potential benefit is much greater than the evidence for potential harm. Vaccines are safe and effective for the vast majority of people. SGEM#20 with guest skeptic Dr. Lauren Westafer (@LWestafer) from FOAMCast discussed the issue of flu shots for healthcare workers.

We do not know how effective a vaccine will be, it’s safety or how long the immunity would last at this time.

George Santayana

Dr. Moore and I continued the presentation with a reminder that we should remember our history. We have made mistakes in the past by adopting new technology or treatments too soon in medicine. There are examples of when the treatment was properly studied it was found not to work or even worse, increase mobility or mortality. It was George Santayana who said “those who cannot remember the past are condemned to repeat it”.

An excellent article was written by Jeaane Lenzer and Shannon Brownlee and published in Issues in Science and Technology. It was titled Pandemic Science Out of Control: A toxic legacy of poor-quality research, media hype, lax regulatory oversight, and vicious partisanship has come home to roost in the search for effective treatments for COVID-19. I would encourage people to read at least the first paragraph.

“On September 14, 1918, in the midst of the worst pandemic in modern history, an article in the New York Times quoted Dr. Rupert Blue, then surgeon general of the US Public Health Service. Blue reported that doctors in many countries were treating their influenza patients with digitalis and the antimalaria drug quinine. There was no evidence that the two drugs were any more effective than folk remedies being used by patients, including cinnamon, goose grease poultices, and salt stuffed up the nose, but doctors were desperate and willing to try just about anything. They would eventually abandon quinine and digitalis as treatments for flu when studies showed they were not only ineffective but caused serious and sometimes deadly side effects.”

Dr. Rob Leeper

I took us back over 200 hundred years to give an example of why it is important to conduct randomized controlled trials rather than relying upon clinical experience and observational data. The study was conducted by Scottish medical student Alexander Hamilton who in 1809 challenged the standard of care, blood letting, for camp fever. He demonstrated that the number needed to treat for harm (NNT) was four. The primary outcome (harm) in this case was death. More details about blood letting and the importance of randomization can be found on the SGEM Xtra with Dr. Rob Leeper.

The CAEP Town Hall on COVID-19 Treatments ended with an excellent article from the NEJM. It was a perspective piece written by Zagury-Orly and Schwartzstein called: A Reminder to Reason. I would highly suggest reading the entire article but the last paragraph gives a powerful statement.

“We are living through an unprecedented biopsychosocial crisis; physicians must be the voice of reason and lead by example. We must reason critically and reflect on the biases that may influence our thinking processes, critically appraise evidence in deciding how to treat patients, and use anecdotal observations only to generate hypotheses for trials that can be conducted with clinical equipoise. We must act swiftly but carefully, with caution and reason.”

The SGEM will be back next episode doing a structured critical appraisal of a recent publication. Trying to cut the knowledge translation window down from over ten years to less than one year using the power of social media. Ultimately we want patients to get the best care, based on the best evidence.