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Review 1: "Defective neutralizing antibody response to SARS-CoV-2 in vaccinated dialysis patients"

Reviewer: Michael Jahn and Johannes Korth (University of Duisburg-Essen) | 📗📗📗📗◻️

Published onMar 15, 2022
Review 1: "Defective neutralizing antibody response to SARS-CoV-2 in vaccinated dialysis patients"
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key-enterThis Pub is a Review of
Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients
Description

AbstractPatients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

Methods and data certainly justify the study’s claims. The overall conclusion is that dialysis patients should be considered for an additional boost and other therapeutic strategies, including early immunotherapy with monoclonal antibodies due to reduced neutralizing activity and delayed affinity maturation of SARS-CoV-2 S-specific B cells can be taken seriously.

However, the classifications of antibody titers as “no“-“low“-“high“ and the classification of neutralizing activity into “no“, “low“, “moderate“ and “high“ appear somewhat arbitrary. The reader cannot understand why antibody titers and neutralizing activities were evaluated as ordinal variables and not as metric variables. Please specify the approach in the methods section in order to make your results more comprehensible and reproducible. Otherwise, one gets the impression that the boundary between low-responder and high-responder was chosen until a statistical significance is reached.

Furthermore, I think that the equation of low-responders with non-responders in the evaluation of the results is problematic, already from a purely semantic point of view. To my knowledge, based on the existing literature it can be assumed that the immune response of low-responders differs from that of non-responders. The discussion should be improved in this area. In addition, the authors should also address the not yet fully elucidated role of T cell activity in the immune responses triggered by SARS-CoV-2 vaccines.  

Finally, the authors declare, “Based on these data, we calculated that the fraction of dialysis patients non-responding to the vaccine further increased to 77% in the case of the Delta variant.” Even after an intensive study of the manuscript, I could not see what this statement was based on. I suspect, however, that this information refers to the activity of the neutralizing antibodies against the delta variant. Maybe, Figure 2 could be extended to visualize these data.

Overall I consider the manuscript as reliable. It confirms previous understanding and sufficiently takes into account the current literature. The recommended actions could be better elaborated in the manuscript.

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