Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses, 2023, Nayyerabadi et al.

SNT Gatchaman

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Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses
Maryam Nayyerabadi; Lyvia Fourcade; Swarali A. Joshi; Prabha Chandrasekaran; Arpita Chakravarti; Chantal Massé; Marie-Lorna Paul; Joanie Houle; Amina M. Boubekeur; Charlotte DuSablon; Valérie Boudreau; Danijela Bovan; Emma Darbinian; Emilia Aïsha Coleman; Sandra Vinci; Jean-Pierre Routy; Pierre-Olivier Hétu; Johanne Poudrier; Emilia Liana Falcone

Background
Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses and viral persistence is unclear.

Methods
In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems and psychological well-being scores before, and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood.

Results
COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs. post-vaccination: 3.92 ± 4.02; p<0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs. post-vaccination: 1.89 ± 1.12; p<0.001), and increases in WHO-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs. post-vaccination: 56.15 ± 22.83; p<0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1β and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity towards SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination.

Conclusions
Our study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.


Link | PDF (International Journal of Infectious Diseases)
 
In this prospective observational cohort study, we included 83 participants previously infected with SARS-CoV-2 who were diagnosed with PCC according to the WHO clinical case definition

Of the 83 participants included in this study, 44 had not yet received a COVID-19 vaccine at the inclusion visit (unvaccinated), while the remaining 39 had already received 1 or 2 doses.
 
Highlights
COVID-19 vaccination post-PCC reduced number of symptoms and increased well-being
COVID-19 vaccination post-PCC down-regulated systemic markers of inflammation
COVID-19 vaccination post-PCC did not abrogate the persistence of viral products
A viral reservoir not cleared by one or two vaccine doses may persist

While the underpinnings of PCC remain to be fully elucidated, viral persistence has been proposed as a potential driver of PCC symptoms in both adults and children [13, 14]. Viral proteins and/or RNA have been detected in intestinal tissue and stool more than 4 months post-infection [15], and in other tissue including skin, appendix, liver, lung and breast [16, 17]. One study detected circulating SARS-CoV-2 spike antigen in 60% of patients with PCC up to 12 months post-infection compared to 0% of patients infected with SARS-CoV-2 without PCC [18]. Persistence of the SARS-CoV-2 spike (S)1 in peripheral blood monocytes from patients with PCC has been observed 15 months post-infection [19]. These data suggest that viral persistence may sustain inflammation and/or immune dysregulation causing PCC.

Participants were enrolled any time between 3 and 6 months from the date of COVID-19 diagnosis with follow-up visits at 12 and 24 months. The median time elapsed between first vaccine dose and study visit was 61.5 days (IQR 22-68) and that between a second vaccine dose and study visit was 20.5 days (IQR 18-32.5).

Canadian research
It's good that a study of the impact of vaccinations on Long covid has been done, as there has been a lot of speculation. But, this design doesn't allow the authors to make the claims that they have in 'Highlights'. With no controls, we can't know if the time elapsed between the baseline and the study visit after the vaccine alone accounts for the reduction in symptoms.
 
Of the 83 participants included in this study, 44 had not yet received a COVID-19 vaccine at the inclusion visit (unvaccinated), while the remaining 39 had already received 1 or 2 doses. Of the 44 unvaccinated participants, 39 were also evaluated after 1 (n=23) and/or 2 (n=16) vaccine doses (longitudinal analysis). We also performed a cross-sectional analysis comparing all unvaccinated participants (n=44) with those having received 1 (n=61) or 2 vaccine doses (n=39).

I'm not sure how you get 16 unvaccinated participants @EndME? 44 of the 83 participants started the study unvaccinated - and they were assessed at baseline. Of those 44, 39 of them were then evaluated after 1 vaccination.
 
They "found no significant difference in plasma levels of SARS-CoV-2 spike and nucleocapsid proteins in participants pre- compared to post-vaccination"

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It seems there are also some different methods to determine whether the spike protein is vaccine induced or virally induced. It would be nice to see this included in studies as this could makes the whole spike amount pre- and post-vaccination debate redundant if the results from this study are to believed.
 
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