Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Abstract

Patients 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 (HD) 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-naive HD patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity, consistent with a delayed affinity maturation of SARS-CoV-2 S-specific B cells. These data indicate that dialysis patients should be considered for an additional boost and other therapeutic strategies, including early immunotherapy with monoclonal antibodies.

COVID-19 in dialysis: clinical impact, immune response, prevention, and treatment

“…Data in hemodialysis patients are limited. The neutralizing activity of serum taken 3 weeks after the second BNT162b2 or mRNA-1273 dose in dialysis patients was significantly lower against Beta than Alpha 88 , and against Delta than the wild-type virus 89 . Although BNT161B2 vaccination induced comparable neutralizing response against VOC in dialysis and non-dialysis patients, the adenoviral-based vaccine AZD1222 (AstraZeneca) had lower immunogenicity 90 .…”

Neutralization assays for SARS-CoV-2

“…The sample size in some studies was as low as <10 individuals 30 38 48 81 94 86 120 , and therefore, such studies are less likely to yield reliable information and meaningful conclusions. It is important to include a statistically appropriate sample size with logical assumptions for reliable estimates with narrow confidence intervals and good precision.…”