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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Scientists are looking for the biological causes underlying the symptoms of post-COVID conditions (long COVID). A recent preprint reveals the results of a study exploring the state of patients’ immune systems after acute COVID-19. The authors found that patients with long COVID symptoms, such as fatigue, brain fog (i.e., cognitive impairment), and nervous system dysfunction, have low cortisol levels and “exhausted” T cells. Understanding these causes could lead to more directed trials of potential treatments. (See Topics to Watch for one such treatment.)  

These biomarkers are also found in patients with myalgic encephalomyelitis/chronic fatigue syndrome and serve as a reminder that many people are living with postinfectious conditions. A recent electronic health record study matched the records of 1.25 million post-COVID-19 patients with the records of an equal number of patients who had experienced other respiratory infections, but not COVID-19. Mood disorders, such as depression and anxiety, may be no more common in people who have had COVID-19 than in people who have had other respiratory infections, but the risk of psychosis, dementia, brain fog, and seizures appears to be higher for the two-year period after a person has had COVID-19. 

In response to the continuing burden patients and their families are facing, the United States has launched a National Research Action Plan on Long COVID and published a report on Services and Supports for Longer-Term Impacts of COVID-19.

Ivabradine for Treatment of Post-COVID-19 Postural Orthostatic Tachycardia Syndrome

At a Glance

  • Ivabradine is a heart rate–lowering medication the US Food and Drug Administration (FDA) approved for treating heart failure. It is currently being investigated as a treatment for post-COVID postural orthostatic tachycardia syndrome (POTS).
  • POTS is a debilitating condition characterized by an excessively high heart rate upon standing, contributing to fatigue, headache, and brain fog.
  • Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that lowers heart rate by selectively blocking the channel responsible for the cardiac pacemaker current.
  • Preliminary findings from a phase 3 clinical trial in patients with hyperadrenergic POTS suggest that ivabradine might also be applied to alleviating symptoms in patients with post-COVID POTS.
  • A phase 4 clinical trial scheduled to begin enrollment in September 2022 will evaluate whether ivabradine effectively lowers standing heart rate in adults with post-COVID POTS. Primary completion is expected in September 2024.

OP-101 to Treat Severe COVID-19

At a Glance

  • Hyperinflammation caused by severe COVID-19 is associated with serious illness. Dexamethasone therapy causes broad immune suppression, possibly leading to significant adverse effects such as secondary infections.
  • OP-101 uses a novel, targeted carrier molecule to deliver N-acetyl-cysteine (NAC) directly to activated, proinflammatory immune cells.
  • NAC is an amino acid derivative with demonstrated antioxidant, anti-inflammatory, and immune-modulating properties. OP-101 is designed to increase the bioavailability of NAC at sites of inflammation, including the central nervous system (CNS).
  • Top-line data show that a single intravenous infusion of OP-101 was well tolerated and reduced the risk of death or mechanical ventilation, as well as biomarkers of brain injury and systemic inflammation characteristic of severe COVID-19 infection and its lingering symptoms.
  • Regulatory meetings between the developer and FDA are planned for the fourth quarter of 2022.

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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

Posted: August 26, 2022

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