#214 COVID Cakes 3: Llamas, Remdesivir, Strokes, the Future, and More!

May 18, 2020 | By Emi Okamoto

We talk Llama Antibodies, Remdesivir and Critical Appraisal Pearls

Elevate your critical appraisal skills as we review the first RCT of remdesivir and share the latest and greatest COVID-19 stories including: Llama antibodies, Stroke statistics, Future Waves, Exit Strategies and Awake Proning. We’re joined by everyone’s favorite Curbsider/internist/epidemiologist, Rahul Ganatra MD MPH (@rbganatra). Rahul provides critical appraisal of the newest randomized control trial (RCT) on remdesivir from the Lancet, and gives us a lesson on why statistical power is so important to consider. We also share updates on strokes, awake proning, pandemic predictions, and we reveal another reason to love llamas (besides those luscious lashes). Llama mia, here we go again!

Show Notes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | CME!

Credits

Written and Produced by: Sarah P. Roberts MPH, Rahul Ganatra MD, MPH, Emi Okamoto MD, Paul Williams MD and Matthew Watto MD

Cover Art: Beth Garbitelli

Hosts: Matthew Watto MD, Paul Williams MD, Rahul Ganatra MD MPH, Emi Okamoto MD , Sarah P. Roberts MPH, 

Editor: Matthew Watto MD (written materials); Clair Morgan of nodderly.com

Sponsors

We are excited to announce that the Curbsiders are now partnering with VCU Health Continuing Education to offer continuing education credits for physicians and other healthcare professionals. Check out curbsiders.vcuhealth.org for more information.

Time Stamps

• 00:00 Intro
• 02:10 Fun animal facts: Llama antibodies
• 09:10 Remdesivir RCT by Wang et al
• 12:40 Power and Sample Size
• 16:32 Baseline Characteristics, Results and Author’s conclusions
• 19:15 Rahul’s conclusions: How chance and bias affected the results
• 24:00 Right censoring; Viral load and timing of antivirals
• 30:30 Final thoughts on Remdesivir RCT by Wang et al; Looking ahead to the NIAID (ACTT) trial
• 33:53 Are patients really having fewer strokes and heart attacks?
• 38:20 Awake proning
• 43:30 Paul teaches us not to use the term “happy hypoxemic”
• 45:00 CIDRAP viewpoint on future waves and exit strategies
• 50:22 Outro

COVID Cakes 3 Show Notes 

Llama antibodies:

Wrapp, D et al. Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies. Cell. May 28, 2020. 

Researchers in Belgium found that antibodies from a llama (named Winter) immunized with coronavirus proteins were able to neutralize SARS-CoV-2 in cell cultures. The study was published in Cell and covered by the New York Times. Neutralizing antibodies are important as they inhibit the receptor binding and fusion, stopping viral entry into cells.

Remdesivir Rundown

Wang, Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. April 29, 2020. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext]

For a step-by-step breakdown of the study, follow along with Dr Ganatra (@rbganatra) on his twitter learning thread (hashtag: #HowIReadThisPaper).

Bottom line: 

RDV was not associated with reduced time to clinical improvement in patients hospitalized with COVID-19. The study suffered from a Lack of power after enrollment stopped early. Additionally, baseline imbalances suggest the RDV group was sicker. Both issues raise the likelihood of a false negative result. Larger studies are needed. Watch out for future studies: NIAID (ACTT) trial and NIAID (ACTT 2 trial of remdesivir plus baricitinib) 

COVID and Stroke

Kansagra AP, Goyal MS, Hamilton S, Albers GW. Collateral Effect of Covid-19 on Stroke Evaluation in the United States. N Engl J Med. Published online May 8, 2020. doi:10.1056/NEJMc2014816

• Some evidence suggesting stroke patients are delaying care due to concerns about receiving treatment during the pandemic
• AHA has released public service announcements in English and Spanish intended to encourage community members to seek care if they have any stroke symptoms

Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020;382(20):e60. doi:10.1056/NEJMc2009787

• Emerging reports of stroke cases among young (<50 yrs old) COVID-19 + patients
• Recent New York Times article details the illness and slow recovery of a 27 year old EMT who fell ill with COVID-19 before experiencing a stroke 

Bottom line: 

Encourage patients and community members to seek immediate care if they experience even mild potential stroke symptoms; be alert for possible stroke symptoms in younger, previously healthy patients who are tested or presumed positive for COVID-19 

Awake Proning

Caputo ND et al. Early self-proning in awake, non-intubated patients in the emergency department: A single ED’s experience during the COVID-19 pandemic. Acad Emerg Med. Apr 22, 2020.

• “Apathetic hypoxia” is common (decreased O2, no distress, +/- tachypnea, otherwise clinically stable). Paul rightly notes, afflicted individuals should not be defined by their condition or their supposed (and unlikely) mental state (“happy hypoxics”). 
• Who was included in this sequential case series report? N = 50 persons admitted to an NYC emergency room in March with hypoxemia after O2 and SARS-CoV2 diagnosis. All clinically able to self-prone safely, and likely qualified for “early intubation” otherwise.
• Median oxygen saturations on arrival: 80%, pre-prone on ~5L O2 via nasal cannula or non-rebreather: 84%, post prone: 94%. 13 needed intubation within 24h, including 7 within the first hour.
• Watch out for more clinical trials, and find this in some guidelines: Intensive Care Society Guidance for Prone Positioning of the Conscious COVID Patient (UK based) and ASTMH include in guidelines for respiratory support during COVID

Bottom line: 

Worth trying if vigilant monitoring and frequent reassessments! Recommended 30-120 minutes prone, and changing between prone, lateral decubitus, and sitting. No cost and minimal risk.

The pandemic’s future

Part 1 of CIDRAP discussing 3 possible scenarios for course of pandemic 

Part 2 of CIDRAP discussing principles of crisis communication as well as possible ways to come out of quarantine and the likely repercussions that balance illness/death and economic recovery (see blue box below)

Where is this all going? Researchers from the Center for Infectious Disease Research and Policy (CIDRAP) extrapolate historical data from prior influenza pandemics to predict possible future scenarios for COVID-19. Be aware, the outbreak will likely last 18-24 months, nothing that it likely won’t end before 60-70% of the population is immune. Three scenarios describe future waves of the outbreak, which will depend much on control measures and other factors, and the authors advise leaders to prepare for the worst (a larger wave this fall 2020).

Bottom line: 

This pandemic will likely last for 18-24 months and multiple wave patterns are possible (based on knowledge from previous pandemics). Relaxing social distancing measures is a trade off between economics and health and safety. 

Goal

Listeners will hone their skills in critical appraisal as they update themselves on all things COVID-19

Learning objectives

After listening to this episode listeners will…

1. Critically appraise recent research on remdesivir as a treatment for COVID-19
2. Recognize the consequences of COVID-19 on strokes
3. Discuss the potential benefits of proning for COVID-19 patients
4. Describe different scenarios likely for the pandemic’s future

Disclosures

The Curbsiders report no relevant financial disclosures. 

Citation

Ganatra R, Okamoto E, Williams P, Roberts SP, Watto MF. “#214 COVID Cakes 3: Llamas, Remdesivir, Strokes, Predicting the Future, and More!”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list May 18, 2020.