COVID-19 Intelligence Report: Emerging Conversations

• 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the finding of the earlier study in NEJM that found no increased risk of death in patients on ACEs/ARBs - a study that was retracted.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. 

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).

• Despite a documented spike in community spread of Covid-19 syndrome, Mayor Bowser says DC may still reopen on May 29^th.   See: https://dcist.com/story/20/05/25/coronavirus-latest-bowser-says-d-c-may-still-reopen-on-may-29/#bowsermay25

• Are Pregnant Women at higher risk?  In contrast to the recent paper reporting pathology findings in placentas, many studies indicate good outcomes of pregnant patients. https://www.medrxiv.org/content/10.1101/2020.05.08.20089268v1