The breadth of the neutralizing antibody response to original SARS-CoV-2 infection is linked to the presence of Long COVID symptoms, 2023, Buck et al.

The breadth of the neutralizing antibody response to original SARS-CoV-2 infection is linked to the presence of Long COVID symptoms
Amanda M. Buck; Amelia N. Deitchman; Saki Takahashi; Scott Lu; Sarah A. Goldberg; Aaron Bodansky; Andrew Kung; Rebecca Hoh; Meghann C. Williams; Marian Kerbleski; David P. Maison; Tyler-Marie Deveau; Sadie E. Munter; James Lombardo; Terri Wrin; Christos J. Petropoulos; Matthew S. Durstenfeld; Priscilla Y. Hsue; J. Daniel Kelly; Bryan Greenhouse; Jeffrey N. Martin; Steven G. Deeks; Michael J. Peluso; Timothy J. Henrich

The associations between longitudinal dynamics and the breadth of SARS‐CoV‐2 neutralizing antibody (nAb) response with various Long COVID phenotypes before vaccination are not known. The capacity of antibodies to cross‐neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms.

We measured longitudinal neutralizing and cross‐neutralizing antibody responses to pre‐ and post‐SARS‐CoV‐2 Omicron variants in participants infected early in the COVID‐19 pandemic, before widespread rollout of SARS‐CoV‐2 vaccines. Cross‐sectional regression models adjusted for clinical covariates and longitudinal mixedeffects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms, as well as Long COVID phenotypes.

We identified several novel relationships between SARSCoV‐2 antibody neutralization and the presence of Long COVID symptoms. Specifically, we show that, although nAb responses to the original, infecting strain of SARS‐CoV‐2 were not associated with Long COVID in cross‐sectional analyses, cross‐neutralization ID 50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of Long COVID and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with Long COVID phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants.

Our findings suggest that relationships between various immune responses and Long COVID are likely complex but may involve the breadth of antibody neutralization responses.

Link | PDF (Journal of Medical Virology)

 

I found this hard to interpret, the language is not readily congruent with a logical thought process.

Here is an example. The sentence starts by substituting the subject of the sentence.

The subject is "the rapid emergence" ~ of Omicron variants. This emergence is a singular phenomenon but the sentence uses the plural form of "result" referring no doubt to the multiple variants, which is an incoherent linguistic structure. This demonstrates linguistic confusion and poor sentence structure, present throughout the document.

Given my previous employment as a TEFL teacher I would tentatively suggest a better use of English as follows.

With regard to the science being discussed, this sentence appears, by one interpretation, to suggest that the evasion of neutralising antibodies by Omicron variants results from prior infection with other variants. This is a significant principle and is discussed in a paper referenced by the paper this paper refers to as ref#25, as ref#5 of ref#25. This is presumably what the author was trying to say though it is a matter of debate whether they actually said it!?

ref#25
https://www.jci.org/articles/view/164303
"Neutralizing antibody responses in patients hospitalized with SARS-CoV-2 Delta or Omicron infection" Linderman SL, Lai L, Bocangel Gamarra EL, et al.

ref#5 of ref#25
https://www.science.org/doi/10.1126/science.abq1841
"Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure" Reynolds CJ, et al.

I dont like the term imprinting, it fails to give adequate regard to the process of antigen binding antibody development as a process involving the random reassortment of gene sequences, resulting in unique antibodies for every individual. Adaptive immunity is not simply the product of an imprint as if it were a potato print.

IMHO the garbled language used in this paper, for unknown reasons, is based on science which has its own basis in studies of approximately n=400 health care workers in London, at most and often less. I think replicability has to be an issue here. Investigators ought to establish replicable facts in multiple cohorts and locations before waxing lyrical. This kind of publication seems speculative and hasty on the nature of longCOVID but these observations are worth investigating to verify them so I would tend to agree with the authors conclusion that more studies need to be undertaken into both the immunogenicity of infection and vaccination patterns towards different variants and the subject of this paper, the relationship between immunogenicity and longCOVID.

Well thats me done for the day, hope it makes sense.

 

This seems like it might just be a multiple comparisons problem, because they checked if a whole lot of things were correlated and found a few closely related things were, which is not surprising. Their analysis is not that there is a correlation between the neutralization of BA.5 as a continuous variable, but specifically correlating being in the top 15% for that variable with having LC symptoms, which seems like a weird thing to do when more than half of the cohort has LC.