Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID, 2024, Iwasaki et al

[EndME]

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID

Abstract
Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology.

Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination.

Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-β and CNTF, among soluble analytes.

Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

https://www.medrxiv.org/content/10.1101/2024.01.11.24300929v1

 

[EndME]

Of course the small sample size and lack of controls makes it impossible to say too much about these results. Maybe this can be followed-up by a larger and controlled study, but if that was worth it they probably would have gone for such a study straightaway.

What I definitely learnt: I never knew that one could spell "naive" as "naïve".

 

[SNT Gatchaman]

What I definitely learnt: I never knew that one could spell "naive" as "naïve".

How meta

 

[SNT Gatchaman]

Interesting to note how the LC patients didn't have PEM in their top 10 symptoms initially, though mostly did at follow-up. There may have been some confusion with the intolerance of/inability to exercise choice though.

 

[NelliePledge]

Interesting to note how the LC patients didn't have PEM in their top 10 symptoms initially, though mostly did at follow-up. There may have been some confusion with the intolerance of/inability to exercise choice though.

I didn’t really register what PEM really was until I started reading materials from ME Association which would have been towards the end of the first year after I got diagnosed. So this doesn’t surprise me.

 

[Kitty]

I never knew that one could spell "naive" as "naïve".

It used to annoy me like crazy when I couldn't find the diaeresis on a keyboard.

Now I just wish I had the energy to be annoyed!

 

[Kitty]

I didn’t really register what PEM really was until I started reading materials from ME Association which would have been towards the end of the first year after I got diagnosed.

Same here. I'd had it for 30 years before I even knew it existed as a concept.

 

[DokaGirl]

@NelliePledge and @Kitty

Me too!

I'd read as much as I could find on ME, but for many years, I never came across the concept/term PEM. There were lots of symptoms discussed in the stuff I read, but no mention of PEM, until much later on.

 

[NelliePledge]

@NelliePledge and @Kitty

Me too!

I'd read as much as I could find on ME, but for many years, I never came across the concept/term PEM. There were lots of symptoms discussed in the stuff I read, but no mention of PEM, until much later on.

Probably because a lot of PWME and clinicians don’t look much beyond fatigue as a description of what’s wrong when as we know it’s a whole bundle of things that are affected

 

[DokaGirl]

Probably because a lot of PWME and clinicians don’t look much beyond fatigue as a description of what’s wrong when as we know it’s a whole bundle of things that are affected

Exactly!

There was, and still is incorrectly, a lot of focus on fatigue. Very plainly, the stigmatizing term "chronic fatigue syndrome", greatly assisted in misinforming about this debilitating, biomedical disease.

 

[Sean]

I didn’t really register what PEM really was until I started reading materials from ME Association which would have been towards the end of the first year after I got diagnosed. So this doesn’t surprise me.

I first learned the term 4 years into it, and it was a real shock of recognition, light bulb turning on moment.

 

[Nightsong]

Now published (Nature Communications Medicine, May 2025, open access):

Link | PDF

Background
The symptomatic and immune responses to COVID-19 vaccination of people with Long COVID are poorly characterized.

Methods
In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination.

Results
At 12 weeks post-vaccination, self-reported improved health is seen in 10 out of 16 participants, 3 have no change, and 3 have worse health although 2 report transient improvement after vaccination. One participant reporting worse health was hospitalized twice with chest pain (after each dose). Symptom outcomes are most associated with plasma biosignatures. Higher baseline sIL-6R is associated with symptom improvement, and stably elevated levels of IFN-β and CNTF are associated with no improvement. Significant elevation in SARS-CoV-2-specific TCRs and spike protein-specific IgG are observed at 6 and 12 weeks after vaccination. No changes in reactivities are observed against herpes viruses and self-antigens.

Conclusions
In this study of 16 people with Long COVID, vaccination is associated with increased SARS-CoV-2 spike protein-specific IgG and T cell expansion in most participants. Specific immune features are associated with symptom change after vaccination and most participants experience improved health or no change following vaccination.

Plain language summary
The impact of the COVID-19 vaccine on unvaccinated individuals suffering from Long COVID is uncertain. This study assessed the experience and biological markers of 16 unvaccinated participants with Long COVID. A total of 10 participants had improved health after vaccination, three reported worsening health, with one hospitalized twice with chest pain. Vaccination boosted the body’s immune responses against the virus that causes COVID-19. We identified biological markers that correlate with the changes in overall health after vaccination. Given that the study was small, more research is needed to confirm these results.