Post-Acute Sequelae of COVID (PASC or Long COVID): An Evidenced-based Approach, 2024, Griffin

[Nightsong]

Abstract
While the acute manifestations of infectious diseases are well known, in some individuals, symptoms can either persist or appear after the acute period. Post-viral fatigue syndromes are recognized with other viral infections and are described after COVID-19. We have a growing number of individuals with symptoms that persist for weeks, months, and years. Here, we share the evidence regarding the abnormalities associated with post-acute sequelae of COVID-19 (PASC) and therapeutics. We describe physiological and biochemical abnormalities seen in individuals reporting PASC. We describe the several evidence-based interventions to offer patients. It is expected that this growing understanding of the mechanisms driving PASC, and the benefits seen with certain therapeutics may not only lead to better outcomes for those with PASC but may also have the potential for understanding and treating other post-infectious sequelae.

Open Forum Infectious Disease (August 2024) | https://doi.org/10.1093/ofid/ofae462 | Link | PDF

 

[Nightsong]

Review article based on TWIV / Parasites without Borders / MicrobeTV discussions:

In early 2020, the directors, staff, and contributors at Parasites Without Borders and Microbe TV, two New York-based nonprofits, started following the clinical presentations and literature surrounding COVID-19. These observations and discussions of the literature were initially shared on the podcast This Week in Virology (TWIV) and posted to the Parasites Without Borders website with links to the articles discussed.

The articles for consideration on the podcast and website, and included in this review, were selected by the directors of Parasites Without Borders (Daniel Griffin, Dickson Despommier, Charles Knirsch, Vincent Racaniello, and Peter Hotez) and the directors of MicrobeTV (Vincent Racaniello, Daniel Griffin, Kathy Spindler, and Amy Rosenfeld). Listeners also suggested articles, which were included if the directors found them appropriate. Due to the very high number of articles being published, not all papers could be selected for discussion.

When an article was selected, a literature review using key terms was conducted to identify similar articles for reference during the discussions and review of the articles. This article will follow the history of the growing appreciation of the phases of COVID19 and the tail of manifestations that came to be recognized under the umbrella term Post-acute Sequelae of COVID (PASC) as presented each week. Articles identified and discussed as contributing to this growing understanding in the episodes released from February 2020 to June 1, 2024, are included.

 

[SNT Gatchaman]

Pretty good.

Some patients with Long COVID tolerate and benefit from exercise. In contrast, a number of patients with Long COVID develop post-exertional malaise (PEM) and can be harmed without careful attention and broad recommendations for graded exercise training (GET). Much literature and controversy surround GET and pacing. There are concerns around any benefits of GET as well as potential harms for those with PASC. There is some evidence that, in a properly selected subset of individuals with Long COVID without PEM), there can be some benefits to GET. There is concern that investigations supporting pacing or GET have been poorly designed and just selected patients able to participate rather than proving a general benefit. There is some evidence that inducing post-exertional malaise can be harmful, triggering metabolic disturbances, myopathy, infiltration of amyloid-containing deposits, and focal necrosis.

Cognitive behavioral therapy (CBT) for severe fatigue following COVID-19 is being studied but remains controversial with concerns about study design and a history of recommending this therapy for ME/CFS despite a lack of compelling evidence. There is a genuine concern that broad recommendations for CBT send a dismissive message. The ME/CFS literature does not support any significant or sustained benefit to this CBT and recommending CBT is contradictory to NICE ME/CFS guidelines.

One big challenge to date and going forward is that there is more disinformation than actual information in this area, as many peddle misinformation for personal gain.

 

[SNT Gatchaman]

Much literature and controversy surround GET and pacing

There is concern that investigations supporting pacing or GET have been poorly designed

But again note the confusion of terms generated by the PACE trial, pacing-up etc.

 

[Hutan]

On the idea that most people improve and even recover in the first two years:

One encouraging message is that the majority of people have slowly decreasing symptoms, while only some having highly persistent symptoms.43 The natural history of Long COVID is such that most impacted individuals will improve, with only a minority still having a persistent condition at two years.43-46

43 Servier, C., Porcher, R., Pane, I., Ravaud, P. & Tran, V.T. Trajectories of the evolution of post- COVID-19 condition, up to two years after symptoms onset. Int J Infect Dis 133, 67-74 (2023).
Forum thread
French team. Large prospective study with periodic tracking. Three trajectories of the evolution of post-COVID-19 condition were identified: “high persistent symptoms” (4%), “rapidly decreasing symptoms” (5%), and “slowly decreasing symptoms” (91%).


44 Bowe, B., Xie, Y. & Al-Aly, Z. Postacute sequelae of COVID-19 at 2 years. Nature medicine 29, 2347-2357 (2023).
Forum thread
US Dept of Veterans Affairs. Very large prospective study.
The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals.
Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6–89.6) and 642.8 (95% CI: 596.9–689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9–31.0%) and 21.3% (18.2–24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year.


45 Boscolo-Rizzo, P., et al. Olfactory and Gustatory Function 3 Years After Mild COVID-19—A Cohort Psychophysical Study. JAMA Otolaryngology–Head & Neck Surgery 150, 79-81 (2024).
Paywall and uninformative abstract


46 Demko, Z.O., et al. Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6–12 Months Postinfection. Open Forum Infectious Diseases 11(2024)
John Hopkins Baltimore team
Small study, only 51 participants provided data at 2 year followup.
During the study period, 33% of participants experienced long COVID (had not returned to pre-COVID-19 health status and reported at least 1 symptom >90 days postinfection); 8% had not returned to their pre-COVID-19 health status 24 months postinfection.
Forum thread

 

[rvallee]

One big challenge to date and going forward is that there is more disinformation than actual information in this area, as many peddle misinformation for personal gain.

Sums up the controversy pretty well. Lots of charlatans are taking advantage of patients here, and the worst of them have MDs and medical licenses. And a whole lot of cowards allowing them to dominate the issue despite having delivered absolute fuck all in decades. That's a unique challenge, exists nowhere else in the world than in health care, where it is actually common. So there's no precedent or examples to draw from. Other than in medicine. Where similar examples are never actually dealt with. Hence why they continue without challenge.

 

[Kalliope]

Next week's episode in the podcast TWiV: Clinical update with Dr. Daniel Griffin will be dedicated Long Covid and this paper, according to yesterday's episode.