Review Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infection, 2022, Newell and Waickman

[Hutan]

https://www.sciencedirect.com/science/article/pii/S0952791522000759?via=ihub

Highlights
Post-acute sequelae of SARS-CoV-2 (PASC) are associated with persistent inflammation.
The antigens or other immune stimuli driving PASC are still unclear.
PASC severity and duration is reduced by SARS-CoV-2 vaccination.

Abstract
SARS-CoV-2 infection is known to result in a range of symptoms with varying degrees of acute-phase severity. In a subset of individuals, an equally diverse collection of long-term sequelae has been reported after convalescence. As survivorship and therefore the number of individuals with 'long-COVID' continues to grow, an understanding of the prevalence, origins, and mechanisms of post-acute sequelae manifestation is critically needed.

Here, we will explore proposed roles of the anti-SARS-CoV-2 immune response in the onset, severity, and persistence of SARS-CoV-2 post-acute sequelae. We discuss the potential roles of persistent virus and autoantigens in this syndrome, as well as the contributions of unresolved inflammation and tissue injury. Furthermore, we highlight recent evidence demonstrating the potential benefits of vaccination and immunity in the resolution of post-acute symptoms.

 

[Hutan]

There's claims of higher levels of inflammatory molecules e.g. CRP in Long Covid, to fit with their overall story of inflammation causing prolonged symptoms, but I think findings have been variable and inconclusive.

Unchecked inflammation and dysregulated adaptive immune responses have been associated with long-term sequelae following the resolution of many other viral pathogens, including Ebola, Lassa, Chikungunya, and influenza viruses 18, 19, 20.

Ebola - Associations between antibody Fc-mediated effector functions and long-term sequelae in Ebola virus survivors
This paper is a bit interesting. I saw it first and was looking to see if there had been any discussion of it in the literature, and came across this 2022 paper.
Long-lasting severe immune dysfunction in Ebola virus disease survivors
That one looks like it could be worth reading.
Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections
And this one has some interesting references to follow up

 

[Hutan]

Antigen persistence in the absence of viral persistence

Multiple immunological mechanisms exist to retain antigen for the purpose of maturing immunological memory after the resolution of an acute infectious insult 38, 39. Most notably, follicular dendritic cells can retain protein antigens in germinal centers (GCs) within lymph nodes or spleen for months after initial antigen production. Indeed, the long-term retention of SARS-CoV-2 antigen within GCs has been suggested to drive clonal and mutational maturation of memory B cells isolated from convalescent COVID-19 patients 29••, 40•.

A separate study identified reduced total IgM or IgG3 levels as a predictor of PASC risk [41], suggesting that not just the magnitude and affinity, but also the isotype of SARS-CoV-2 Ig may play a role in PASC.