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As People Suffer, Little is Understood


March 15 marks Long COVID Awareness Day. The day is designed to shed greater light on a mysterious condition, post-acute Sequelae of SARS-CoV-2 (PASC) or Long COVID. The medical condition is particularly vexing as it does not have any definitive diagnostic tests, therapeutic treatments, and limited clinical information for providers and patients to really understand it. Along with a multitude of symptoms, one of the significant health issues associated with the condition is neurological. Specifically, brain fog is often been a persistent symptom of the condition. In recent commentary published in the New England Journal of Medicine, clinicians remarked on the studies looking at the cognitive issues associated with Long COVID.1

The authors referenced an online assessment tool that looked at cognitive function in patients with COVID-19.1

“Participants with unresolved persistent symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ,” the authors wrote.1

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” the authors concluded.

Identifying Biomarkers for Long COVID
One of the ongoing challenges is the inability of medical science to land on a direct diagnosis and there are no definitive tests to identify the condition. Much like people who experience chronic fatigue syndrome (CFS), it is difficult to understand its enigmatic nature, and people with either of these post-viral conditions can suffer for months or even years.

There has been some research around potential biomarkers in helping to potentially identify the condition. One study looked at blood serum proteins. Carlo Cervia-Hasler et al, showed that patients experiencing Long COVID, “exhibited changes to blood serum proteins indicating activation of the immune system’s complement cascade, altered coagulation, and tissue injury.”2

This was a multicenter study, which consisted of 39 healthy control patients and 113 COVID-19 patients who were followed-up to 1 year after initial confirmation of infection through PCR test. After confirmation of acute infection, patients were seen for follow-up appointments at 6 months and 12 months to identify biomarkers associated with Long COVID. At the 6-month follow-up, 40 patients had Long COVID symptoms.2

At the recent Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, CO, another study looked at blood-related biomarkers. Investigators collected blood samples from 3 different groups: participants with Long COVID with symptoms duration > 3 months with 30 in this group; patients who were previously infected with COVID-19 but without persistent symptoms (10 people); and healthy donors (20 people).2

Flow cytometry was utilized to quantify MK frequency. The investigators analyzed platelets and blood MKs for microclots, and the presence of spike protein and SARS-CoV-2 RNA. Spike and serotonin were quantified in plasma.2

“The frequency of CD41+ MKs in peripheral blood mononucleated cells (PBMCs) was significantly higher than healthy donors (0.28± 0.05 versus 0.03± 0.02) as a sign of MK infection, as we previously shown in acutely infected individuals with SARS-CoV-2 in platelets. Accordingly, in all samples analyzed, circulating MK in Long COVID sheltered both Spike and SARS-CoV-2 ssRNA, but also dsRNA suggestive of viral replication,” the investigators wrote.2

Long COVID: Can it be Treated?
There is no FDA-approved therapy for Long COVID and treatment may be more about trying to ameliorate individual symptoms, when possible.

Interestingly, new data around the antiviral, remdesivir, and Long COVID was published at CROI.

Specifically, investigators performed a retrospective cohort study with information from HealthVerity database. Study participants included individuals 12 years of age and older who were hospitalized for COVID-19 for 2 days or more during a study period between May 1, 2020, and September 30, 2021. Remdesivir exposure was measured on day 1 or 2 of hospitalization, and symptoms and diagnoses associated with Long COVID occurred 90 to 270 days post hospitalization.3

“RDV treatment during the first 2 days of hospitalization (vs no RDV treatment during the first 2 days of hospitalization) was associated with lower relative hazards for any [post COVID conditions] PCC symptom/ diagnosis in patients aged <65 years (HR, 0.90 [95% CI, 0.86-0.93];) and in patients aged ≥65 years (HR, 0.90 [95% CI, 0.86-0.95],” the investigators wrote.3

Another Option
It remains to be seen if this post-viral condition will continue to be a public health issue long-term and what inroads will be made for diagnostics and therapies. In the meantime, the federal government has recognized Long COVID as a condition that could result in a disability under the Americans with Disabilities Act (ADA). The US Department of Health and Human Services has resources and more information on its website. (See the Long COVID resources above. 

References

1 Al-Aly Z, Rosen CJ. Long Covid and Impaired Cognition – More Evidence and More Work to Do. N Engl J Med. 2024;390(9):858-860. doi:10.1056/NEJMe2400189

2. Parkinson J. Potential Biomarkers of Long COVID. ContagionLive. March 4, 2024. Accessed March 15, 2024.

3. Parkinson J. Remdesivir Associated With Lower Risk of Long COVID in Hospitalized Patients. ContagionLive. March 5, 2024. Accessed March 15, 2024.



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