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COVID-19 Intelligence Report: Emerging Conversations

This section aims to spread emerging ideas from the professional rumor mill, in an effort to keep decision makers apprised of topics that are brewing. While this information may become part of the COVID pedagogy, it may represent less rigorously scientific and/or non-evidence-based propositions. They may not be peer reviewed. Accordingly, we do not recommend incorporation into clinical guidelines.

June 29, 2020

  • As mentioned last week, preliminary results from the RECOVERY trial show mortality reduction in patients on oxygen or invasive mechanical ventilation who received dexamethasone 6 mg given once daily for up to ten days vs. usual case. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). There was no benefit to people without an oxygen requirement and may be a trend towards harm in that group.
    • MGH FLARE summary of evidence on steroids, ARDS, and COVID-19 suggest clinicians should “strongly consider the use of dexamethasone in their COVID-19 patients with an oxygen requirement or hypoxemic respiratory failure.”
  • A study looking at the association between renin–angiotensin system inhibitors and COVID-19 complications found the risk of admission to ICU or death prior to ICU admission was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. Further study on this potential link needs to be done. This is counter to the finding of the earlier study in NEJM that found no increased risk of death in patients on ACEs/ARBs - a study that was retracted.
  • Mounting clues suggest the coronavirus might trigger diabetes: There have been reports of patients who spontaneously developed diabetes after being infected with SARS-CoV-2. A recent experimental study in miniature lab-grown pancreases published last week suggests that the virus might trigger diabetes by damaging the cells that control blood sugar. An online registry has been developed to evaluate COVID-19 related diabetes further. 

June 1, 2020

Title: Editorial Comment - Face coverings for the public: Laying straw men to rest

Publisher: Journal of Evaluation in Clinical Practice

Publication Date: May 26, 2020 URL: https://doi.org/10.1111/jep.13415

Key Takeaway: This is an evidence based narrative rebuttal of criticisms of the effectiveness of face coverings/masks in preventing the transmission of the Coronavirus/COVID-19. Evidence of asymptomatic carriage of Sars‐CoV‐2 is strong and consistent, the public health rationale for the public use of face masks is to minimize forward spread of this virus. The author Dr Trisha Greenhalgh is an expert practitioner of evidence based medicine.

 

Title: Hydroxychloroquine (HCQ) or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Publisher: The Lancet

Publication Date: May 22, 2020

URL: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180- 6/fulltext

Key Takeaway: This is a report from a multinational registry that comprised data from 671 hospitals in six continents and 15,000 patients who received HCQ or chloroquine were about twice as likely to die compared to controls who did not receive these agents after adjusting for covariates (18.0% for hydroxychloroquine and 16% for chloroquine versus 9.3% for controls). The authors conclude: “We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in- hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.”

NOTE: A group of more than 140 scientists, researchers, and statisticians have written an open letter to the Lancet and the authors of this study raising concerns about the integrity of the results and calling for the release of patient data and for the findings to be validated by the World Health Organization (WHO), or at least one other independent institution. Lancet did issue a correction to some specific data reported but that the overall findings remain unchanged. See: https://www.tctmd.com/news/lancet-covid-19- hydroxychloroquine-study-faces-data-integrity-questions

 

Title: Remdesivir: An Important First Step (Raphael Dolin, MD & Martin Hirsch MD)

Publisher: NEJM

Publication Date: May 27, 2020

URL: https://www.nejm.org/doi/full/10.1056/NEJMe2018715?query=recirc_curatedRelated_article

Key Takeaway: This is an thoughtful editorial by two researchers experienced in HIV therapeutic development about what we currently know, don’t know and need to know about the role of remdesivir looking at the study reported above and the one reported last week (https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=featured_home):

  • Remdesivir’s effect appears to be modest.
  • Timing of initiation of treatment with an antiviral such as remdesivir, as well as the underlying clinical status of the patient, may have important effects on the outcomes of therapy and
  • Since the pathogenesis of Covid-19 involves not only virus replication, but also immunomodulation and inflammation, studies of combination therapy with other antivirals and antiinflammatory agents in appropriate sequence are of high priority (and plans for such studies are already under way).

May 25, 2020

 

May 18, 2020

Title: Study to Determine Incidence of Novel Coronavirus Infection in U.S. Children Begins

Publisher: NIAID News Release

Publication Date: May 4, 2020

URL: https://www.niaid.nih.gov/news-events/study-determine-incidence-novel-coronavirus-infection-us-children-begins

Key Takeaway:  News release on HEROS study to prospectively follow 6000 people from 2000 US families already enrolled in NIH research to look at SARS-CoV-2 infection rates, and subsequent symptom development. An aim of the study is to determine if persons with allergic conditions may be less susceptible to SARS-CoV-2 due to less ACE2 in upper and lower airway cells, based on preliminary evidence.

 

May 11, 2020

Viral Mutations

Title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 (Preprint)

Publisher: bioRxiv

Publication Date: 30 April 3030

URL: https://www.biorxiv.org/content/10.1101/2020.04.29.069054v1

doi: https://doi.org/10.1101/2020.04.29.069054

Key Takeaways: The Spike (S) protein in SARS-CoV-2 mediates the infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics.  A mutation in this protein has been documented (along with over a dozen others).  It began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. The authors also present evidence of recombination between locally circulating strains, indicative of multiple strain infections.  There is concern that this mutation has the potential to facilitate a more infectious strain of COVID, although there is no evidence to that effect at this time.  The report did gain some mainstream media attention as well as a significant critique of the decision to print the information.

 

Epidemiology

Title: COVID-19: The CIDRAP Viewpoint

Publisher: Center for Infectious Disease Research and Policy (CIDRAP), University of Minnesota

Publication Date: 30 April 2020

URL: https://www.cidrap.umn.edu/sites/default/files/public/downloads/cidrap-covid19-viewpoint-part1_0.pdf

(An alternative non-PDF link: https://www.cidrap.umn.edu/covid-19/covid-19-cidrap-viewpoint)

Key Takeaways: The report details possible future pandemic wave scenarios for COVID (see figure 2). Officials should prepare and plan for the worst-case scenario which includes no vaccine availability and little herd immunity.  This includes the need to ensure adequate protection for the healthcare community during future disease peaks

 

Risk communication for COVID should incorporate the concept that there may be resurgences of disease for the next two years

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