Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity 2023 Altmann et al

[Andy]

Abstract

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection. It has been proposed that Long Covid is a consequence of either an excessive or inadequate initial immune response. Here, we analyze SARS-CoV-2 humoral and cellular immunity in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave. Symptom questionnaires allow stratification into those with persistent symptoms and those without for comparison.

During the period up to 18-weeks post-infection, we observe no difference in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses. Also, there is no difference in the profile of antibody waning. Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity. Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality.

Open access, https://www.nature.com/articles/s41467-023-40460-1

 

[EndME]

Haven't read the paper yet, but the question will be whether their analysis was intricate enough to have studied the results presented in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272838/ and https://www.frontiersin.org/articles/10.3389/fimmu.2023.1221961/full.

 

[mariovitali]

Can someone explain whether findings of this paper suggest that there is no "viral reservoir" which some claim is responsible for Long COVID symptoms?

 

[SNT Gatchaman]

The paper suggests evidence is against.

The introduction says —

It has been variously proposed either that Long Covid sufferers are unusual in having especially low adaptive immunity to the virus, or alternatively, that the persistent symptoms may be related to an excessively high and uncontrolled anti-viral response. The ‘high anti-viral response’ hypothesis is potentially compatible with a related hypothesis of Long Covid aetiology, namely that there is a chronic reservoir of persistent SARS-CoV-2 antigen, for example in the gut.

Results/discussion —

We were thus able to compare HCW who had suffered contemporaneous, first-wave, mild/asymptomatic COVID-19, with or without evidence of persistent symptoms, looking at pre-vaccination immunity with respect to: Ab binding response to spike (S) and nucleocapsid (N) during and following the acute infection, as well as neutralizing Ab titers and T cell responses at 4 months after infection. This not only allowed us to investigate whether symptom persistence was associated with especially high or low parameters for these elements of SARS-CoV-2 adaptive immunity acutely or in subsequent months, it also allowed us to use the trajectory of the longitudinal N Ab response as a proxy measurement of whether there was likely to be an ongoing, persistent reservoir of antigen. Antigen persistence might be predicted to correlate with a sustained or rising N Ab response; from first principles, a persistent antigen reservoir may be visible through its immunogenicity and impact on ongoing stimulation of the Ab response to N, and thus a tendency to increased levels.

We initially considered whether the groups who did or did not go on to experience persistent symptoms assessed at 6-months differed in any aspects of their immune response to the virus. With respect to binding Ab to RBD, there was no difference between groups in terms of peak Ab titer, with Ab level similarly maintained in both groups through to week 24. Each group contained a small minority of HCW with a low or undetectable Ab response, as we have previously described. A similar pattern was also evident for the anti N Ab response. We did not find evidence for aberrant anti-viral immunity as a predictor of persistent symptoms and the data also were not strongly supportive either of differential immune waning or of ongoing immune stimulation from a persistent immune reservoir of virus.

They concluded —

That we did not see a differential Ab response in the persistent symptoms group of this cohort might be considered to argue against the ‘persistent antigen reservoir’ hypothesis as commonly causal in Long Covid.