Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients

Abstract

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients

“…Both conditions may facilitate the virus entry and in particular its spread. Although the use of anti-CD20 monoclonal antibodies has been consistently associated with a lower amount of SARS-CoV-2-R-A after vaccination [29][30][31][32], being treated with anti-CD20 monoclonal antibodies was not associated with an increased incidence of breakthrough infection in our study. It is likely that the number of events and in particular of patients who received anti-CD20 monoclonal antibodies within 6 months before starting vaccination (n = 97, 36%) was too low to observe significant differences.…”

“…Several prior studies revealed that among HD patients, CLL patients are characterized by a severe cellular immune dysfunction which translates into a low humoral response rate [24,25] and a severe course of the disease [26,27], although a significant reduction in mortality has been observed in the Omicron era [28]. On the other hand, corticosteroid use has been associated with a lower probability of mounting an adequate humoral response [29]. Both conditions may facilitate the virus entry and in particular its spread.…”

“…Although we do not have a likely explanation for this difference, we can speculate that hormonal differences and/or differences in social behaviors between males and females may explain such differences. Finally, patients free of treatment for at least one year before vaccination experienced a lower incidence, most likely because the probabilities of having a serological response after vaccination are consistently higher [29]. In light of these findings, it seems reasonable to maximize humoral vaccine responses according to the disease status and treatment as recently suggested by the SEHH [15] and that low-evidence-based preexposure prophylaxis recommendations in vaccinated patients with long-lasting monoclonal antibodies should be restricted to patients harboring these conditions instead of its unselective use.…”

SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination

“…This prospective, observational, multicenter registry study was conducted by the Infectious Complications Subcommittee (GRUCINI) of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH-TC). Characteristics of the registry have been published elsewhere in detail [ 4 , 12 ]. Briefly, the registry included consecutive hematological disorders (HD) patients who were vaccinated against SARS-CoV-2 between December 30, 2020 and June 30, 2021 in 21 participating Spanish centers.…”

“…The cumulative incidence of SARS-CoV-2 breakthrough infection at one year after full vaccination was 15.3% [95%, confidence interval (C.I. ), [12][13][14][15][16][17][18]. Cumulative incidence was similar among cell procedures: 21% (95%, C.I.…”