Remission of severe forms of Long Covid following monoclonal antibody (MCA) infusions: A report of signal index cases..., 2024, Scheppke, Klimas et al

Related RCT enrolling via UCSF: An Exploratory, Randomized, Double-Blind Placebo-Controlled Study to Assess the Safety of an Anti-SARS-CoV-2 Monoclonal Antibody and Response to Treatment in Individuals With Long COVID (outSMART-LC)

See also https://classic.clinicaltrials.gov/ct2/show/NCT05877508

This is not the same mAb cocktail as in this paper. Hoping to enrol 30, with 2:1 AER002 vs placebo.

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For the mAb cocktail described in this paper, I am told that a number of people have indicated no effect on LC in various Twitter threads (can't confirm with direct links to those comments). So that might be in keeping with the idea that targeting persistent viral antigen is only helpful in a (small?) subset of pwLC and that other mechanisms dominate. Or these are simply a few spontaneous recoveries unrelated to the mAbs.
 
Isn't it also the case that some people with LC report it resolving after another Covid infection, which is what the three people in this study had? Why is it assumed to be related to the mAbs instead of the infection itself?
 
LarsSG said:
Isn't it also the case that some people with LC report it resolving after another Covid infection
Click to expand...
Yes.

LarsSG said:
which is what the three people in this study had? Why is it assumed to be related to the mAbs instead of the infection itself?
Click to expand...
No. Only one actually was positive. The other two were exposed (presumably close family members) but didn't become positive. The authors also try to cover this point in the supplementary materials.

Appendix B said:
One could also speculate that the acute exposures/re-infections leading to the MCA treatment occurred during the Delta phase and that Delta infection may have been the intervention that changed the long COVID condition. However, now based on extensive clinical observations, that has not been the apparent case for the many other long COVID-19 patients who became re-infected with the Delta variant but did not receive the MCA.
Click to expand...
 
Merged

Full Title: Remission of severe forms of Long Covid following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targetd research, 2024, Nancy G Klimas et al

Highlights
  • Long COVID-19 remains crippling for millions and their families worldwide.
  • The first three index cases of therapeutic complete remission are reported here.
  • Each full remission occurred within a week monoclonal antibody infusion.
  • Remission occurred despite dissimilar past histories, sex, age, illness duration.
  • This has mechanistic implications for treating other post-viral chronic conditions.
Abstract

Objective
Long COVID has afflicted tens of millions globally leaving many previously-healthy persons severely and indefinitely debilitated. The objective here was to report cases of complete, rapid remission of severe forms of long COVID following certain monoclonal antibody (MCA) infusions and review the corresponding pathophysiological implications.

Design
Case histories of the first three index events (among others) are presented. Unaware of others with similar remissions, each subject independently completed personal narratives and standardized surveys regarding demographics/occupation, past history, and the presence and respective severity grading of 33 signs/symptoms associated with long COVID, comparing the presence/severity of those symptoms during the pre-COVID, long-COVID, post-vaccination, and post-MCA phases.

Setting
Patient interviews, e-mails and telephone conversations.

Subjects
Three previously healthy, middle-aged, highly-functioning persons, two women and one man (ages 60, 43, and 63 years respectively) who, post-acute COVID-19 infection, developed chronic, unrelenting fatigue and cognitive impairment along with other severe, disabling symptoms. Each then independently reported incidental and unanticipated complete remissions within days of MCA treatment.

Interventions
The casirivimab/imdevimab cocktail.

Measurements and main results
Irrespective of sex, age, medical history, vaccination status, or illness duration (18, 8 and 5 months, respectively), each subject experienced the same complete remission of their persistent disabling disease within a week of MCA infusion. Each rapidly returned to normal health and previous lifestyles/occupations with normalized exercise tolerance, still sustained to date over two years later.

Conclusions
These index cases provide compelling clinical signals that MCA infusions may be capable of treating long COVID in certain cases, including those with severe debilitation. While the complete and sustained remissions observed here may only apply to long COVID resulting from pre-Delta variants and the specific MCA infused, the striking rapid and complete remissions observed in these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions and long COVID from other variants.

Key points
  • Question: Considering that long COVID-19 has been devastating for many millions worldwide, what is the proposed pathophysiology and are there any effective treatments?

  • Findings: Previously-healthy middle-aged persons who had developed persistent debilitating post-acute SARS-CoV-2 sequelae, each experienced complete remission of their symptoms within days of receiving a specific monoclonal antibody infusion despite relative differences in sex, age, medical history, vaccination status, and long COVID duration.

  • Meaning: Certain monoclonal antibody infusions may be capable of reversing severe long COVID. Beyond providing an effective potential treatment for long COVID, these findings have mechanistic implications for treating other post-viral chronic conditions, including future long COVID variants.




https://www.sciencedirect.com/science/article/pii/S073567572300534X?via=ihub


 
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Medscape: Monoclonal Antibodies: A New Treatment for Long COVID?

quote:

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

  • It stimulates the body to fight off any residual virus. "We suspect that many of these patients simply have levels of virus that are so low they can't be picked up by conventional testing," said Marty. "The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out." This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.

  • It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms "not because of residual virus but because of junky antibodies," said Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. "This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient's cells," she explained.

  • Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. "It may not explain all of the cases of long COVID, but it could make up a subgroup," she said. It's thought that the monoclonal antibodies may perhaps neutralize this reactivation.
 
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