Briefing

The Briefing provides an at-a-glance view of some important developments in the information universe surrounding COVID-19. The views presented here are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders.

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Recent studies by the Centers for Disease Control and Prevention (CDC) indicate that vaccines against COVID-19 have remained effective and that the risk of being hospitalized for COVID-19 is 4.5 times higher for adults who are not fully vaccinated.  Patients requiring hospitalization might benefit from new treatments aimed to supplement standard of care for severe COVID-19 (see Topics to Watch).

Against this background, the science of booster shots is being debated and newer generations of vaccines continue to be tested, including the first ever DNA-based vaccine, recently approved in India.  

A small study from the University of Arkansas for Medical Sciences hints that angiotensin-converting enzyme (ACE)-2 autoantibodies might be a promising target for future treatment of patients with long COVID, although other work is looking to objectively diagnose such patients (see Topics to Watch). A National Institutes of Health (NIH) project called the REsearching COVID to Enhance Recovery (RECOVER) Initiative is working to make future long-COVID studies stronger by creating a meta-cohort that brings together a national study population.

C21 (VP01) to Treat Severe COVID-19 

At a Glance

  • C21 is an investigational oral small molecule angiotensin II type 2 receptor (AT2R) agonist added to standard of care for treating patients hospitalized with severe COVID-19.
  • SARS-CoV-2 binding to ACE2 might cause a loss of function leading to an imbalance in and reduction of the protective effects of the renin-angiotensin-aldosterone system (RAAS). Treatment with C21 purportedly stimulates AT2R and restores the functionality of the RAAS, purportedly promoting antioxidant, anti-inflammatory, anticoagulative, and antifibrotic effects.
  • Preprint data from a phase 2 randomized controlled clinical trial in 106 hospitalized patients found that at day 14, the proportion of patients in the C21 group still requiring supplemental oxygen was significantly reduced by 90%, compared with the placebo group.
  • An ongoing phase 3 randomized trial comparing C21 with placebo in hospitalized adults with severe COVID-19 has a primary completion expected in February 2022.

Corneal Confocal Microscopy to Detect Long COVID

At a Glance

  • Corneal confocal microscopy (CCM) is a noninvasive, ophthalmic imaging technology proposed as a method to identify patients with long COVID more objectively.
  • CCM purportedly detects subtle changes in nerve fibers in the front of the eye that might be linked with other neurologic symptoms of long COVID.
  • An early study found patients with post-COVID neurologic symptoms also had the largest reductions in several types of corneal nerve fibers. Reductions in these corneal nerve fibers were significantly correlated with patients’ scores on a standard long-COVID screening questionnaire.
  • Further research is needed to definitively link corneal nerve changes with long COVID and differentiate it from other potentially preexisting neurologic conditions.

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Commentary in this COVID-19 Scan reflects preliminary views of ECRI Horizon Scanning and internal ECRI stakeholders.
The information contained in this document has not been vetted by other stakeholders.

We welcome your comments on this Scan. Send them by email to [email protected]
or by mail to: Patient-Centered Outcomes Research Institute, 1828 L Street, NW, Suite 900, Washington, DC 20036.


Posted: September 24, 2021

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