#245 COVID Cakes: Masks, Home Testing, Anticoagulation

December 7, 2020 | By Deb Gorth

Why do we have to do this again?

Learn about the latest in COVID-19: Do masks prevent infection?, SARS-CoV-2 home testing, vaccine advice, and how to prevent and treat VTE in COVID-19. Join us as our tzar-of-clinical-appraisal Curbsider/internist/epidemiologist Rahul Ganatra MD MPH (@rbganatra) talks us through the controversial DANMASK-19 trial, plus Watto reports back on his conversation with Dr Parth Rali @parthrali (Temple Lung Center) who helped write the CHEST anticoagulation guidelines for COVID-19.

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Credits

• Producer: Deb Gorth ScM
• Show Notes, Cover Art, and CME by: Deb Gorth ScM and Matthew Watto MD
• Written by: Matthew Watto MD, Paul Williams MD, and Rahul Ganatra MD MPH
• Hosts: Rahul Ganatra MD MPH, Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP
• Editor: Matthew Watto MD (written materials); Clair Morgan of com

Sponsor

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Time Stamps

• 00:00 Intro, disclaimer, Picks of the week* and Vaccine advice
• 08:00 DANMASK-19
• 25:00 Anticoagulation in COVID-19
• 35:06 COVID-19 home PCR testing
• Outro

DANMASK-19 Trial

Bundgard H, Bundgaard JS, et al: Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers. Annals of Internal Medicine 2020.

Question: The DANMASK-19 Trial aimed to assess whether wearing a mask confers the mask wearer a 50% reduction in SARS-CoV-2 infection.

Primary Outcome: SARS-CoV-2 infection measured by antibody positivity, PCR, or hospital diagnosis.

Duration of Followup: One month.

Comparison: This randomized controlled trial compared encouragement to social distance versus encouragement to social distance and wear masks, along with a supply of 50 surgical masks.

Study Population:  Participants were adults spending greater than 3 hours outside the home in Denmark during April and May 2020.

Results: Out of the 4862 participants who completed the trial, 95 total SARS-CoV2 infections were recorded, 42 (1.8%) participants recommended masks and 53 (2.1%) control participants (-0.3 percentage points [95% CI, -1.2 to 0.4; p = 038]). Of the participants recommended masks, 46% reported adherence.

Bottom Line: This negative study failed to show that wearing a mask leads to a 50% relative risk reduction.

Evidence Based Medicine Sidebar: Changes in Test Specificity Have a Large Effect on the Positive Predictive Value of Low Prevalence Diseases

The false-positive rate of any test increases rapidly when outcomes are rare and specificity is much lower than 100%. At a prevalence of 2% and a sensitivity/specificity of 82.5% / 99.5% for the antibody assay used in this study, the positive predictive value (PPV; the proportion of tests that if positive truly mean someone has the infection) is 77%. However, using the specificity reported by the FDA of 97.5%, just 2% lower, the PPV falls to 40%, a reduction of 37%! (The low PPV of a test when there is low prevalence is why we do series testing for diseases like HIV.) This is important for our interpretation of this study, because a PPV of <50% means the majority of all infections diagnosed by serology are likely to be false positives, distributed evenly between groups, thus biasing towards the null hypothesis.

So What?

While this study failed to show that the recommendation to wear a mask confers a risk reduction for SARS-CoV-2 infection to the wearer, to contextualize the DANMASK-19 results, it is important to consider how the study was powered and the effect of low incidence of COVID-19 during the study period. Powering the study for a 50% reduction in infection, an effect more in line with what can be expected from a vaccine, meant that this work would fail to identify a more subtle effect. In addition to the discussion above regarding how incidence/specificity affects PPV, studying rare events is notoriously difficult. A (theoretical) study looking at the efficacy of bulletproof vests will not show a mortality benefit if the incidence of gunshots is low, but that does not mean that bulletproof vests do not protect against gun shots.

Masks work. Looking at county-to-county differences in Kentucky, the CDC reported that mask mandates confer a sizable reduction in COVID-19 incidence (Van Dyke et al 2020). Furthermore, a study modeling the effect of masking on mortality predicts over 100,000 deaths prevented in the US by Feb 2021 if universal masking is achieved (IHME COVID-19 Forecasting Team). See this site for continuously updated IHME projections.

Check out Dr Ganatra’s tweetorial breaking it all down: Link to Rahul’s Thread

Anticoagulation and VTE prevention in COVID-19

Background: Early reports of increased incidence venous thromboembolism (VTE) in patients hospitalized w/COVID-19; even if on anticoagulant prophylaxis. Both microthrombosis and symptomatic VTE occur (Daniel Kaul, NEJM JWatch article June 2, 2020 and Jiménez et al 2020).

CHEST VTE Guidelines for COVID-19 (Moores, 2020)

A panel of experts decided on 13 PICO questions, conducted systematic reviews and made 22 recommendations (based on evidence when available, but ultimately used expert consensus) via a modified Delphi process. NOTE: The following recommendations refer to acutely ill (non-critically ill) patients with COVID-19.

• Use LMWH or fondaparinux for hospitalized patients over unfractionated heparin (UFH) due to once daily dosing (limit HCP exposure)
• DOACs are given lower priority in the hospital given drug-drug interactions (Wiggins, 2020 ) –potentially with remdesivir– and risk of clinical deterioration, renal failure
• Standard dose VTE prophylaxis is recommended over intermediate dosing
• Extended duration VTE prophylaxis is not recommended at this time
• Don’t start full anticoagulation just based on D-dimer levels!
• For outpatients use a DOAC > Vit K antagonist > LMWH (for convenience). Duration = 3 months minimum

NIH Guidelines Antithrombotic therapy

These are in strong agreement with the CHEST guideline

• One slight difference: Extended prophylaxis with DOACs may be considered after discharge if low risk bleeding and high risk VTE (per inclusion criteria used in trials of rivaroxaban 10 mg daily (31-39 days) and betrixaban (35-42 days)
  • Both are FDA approved for non-COVID patients based on things like age (>60-75 yo), D-dimer >2x ULN, previous VTE or cancer, IMPROVE-VTE score (4 factors: age >60, current cancer, previous vte, thrombophilia).

Bottom line: Current recommendations can be broadly interpreted using the same prophylactic anticoagulation for patients hospitalized with COVID-19 as you would for any hospitalized patient.

 What’s next?: Multiple large RCTs for VTE treatment and prevention are ongoing (NCT04498273, NCT04409834 aka COVID-PACT, NCT04373707 aka COVID-DOSE, and NCT04394377) with results expected in the next few months. The CHEST guidelines will be updated again at that time.

COVID-19 Testing PCR vs Antigen, home test kit

PCR

• False-negative rates are 100% on day 1, 67% on day 4, 38% when symptoms begin on day 5, 20% on day 8 (3 days after symptom onset), and rise back up to 66% on day 21 (Kucirka, Annals Int Med 2020 ).
• Sensitivity and specificity of rRT-PCR assays for SARS-CoV-2 also vary between local, commercial, and federal laboratory kits, with best practices still in evolution (ACP COVID-19 Resource guide).

Home test kit

• The FDA authorized an at home test kit.
• Patients collect their own nasal swabs at home for detection of nucleic acid from SARS-CoV-2 (PCR test).
• “Sometimes the swab can feel slightly uncomfortable or tickly. “
• “Rotating the swab 5 times around the inside walls of both nostrils is very important for the test to work properly.”
• The manufacturer claims 94% positive percent agreement and 98% negative percent agreement (PDF handout for Lucira test kit).
• Patients need a prescription from their doctor to get the kit.

COVID-19 Vaccines ARE HERE!

• Bottom line: Take any FDA approved COVID-19 vaccine available to you in the near future. You can always get a booster if one proves superior in the long term. Tell your family and friends “it’s just a matter of staying disciplined for the next couple of months and getting them to the other side” ( Peter Hotez on Fresh Air).

Links*

Links

1. A non-alcoholic IPA from our future(?) non-alcoholic beer sponsors (call us Athletic Brewing Company, please).
2. YouTube working from home fails, pets are a bonus.
3. Check out this great interview with vaccine scientist, Dr Peter Hotez (Baylor).
4. Dolly Parton is a national treasure:
   1. She helped fund a SARS-CoV-2 Vaccine.
   2. She provides COVID-19 economic relief through Mountain Tough.
   3. Dollywood.
   4. She helps promote childhood literacy through her Imagination Library.
   5. She created a web series of her reading bedtime stories.
   6. She was involved in greenlighting Buffy the Vampire Slayer.
   7. Also, Jolene.

Goal

Listeners will learn about the DANMASK-19 trial, the latest on SARS-CoV-2 testing, and current anticoagulation recommendations for patients suffering from COVID-19.

Learning objectives

After listening to this episode listeners will… 

1. Learn about the DANMASK-19 trial.
2. Recognize the importance of power calculations to interpreting a clinical trial.
3. Review the current testing methods for detecting SARS-CoV-2 infection.
4. Appreciate the current anticoagulation recommendations for patients suffering from COVID-19.

Disclosures

Dr Ganatra and The Curbsiders report no relevant financial disclosures

Citation

Ganatra RB, Gorth DJ, Williams PN, Watto MF. “#245 COVID Cakes: Masks, Home Testing, Anticoagulation”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date December 7, 2020.