key: cord-0702549-rznlagol authors: Beerlage, Astrid; Leuzinger, Karoline; Valore, Luca; Mathew, Roby; Junker, Till; Drexler, Beatrice; Passweg, Jakob R.; Hirsch, Hans H.; Halter, Jörg title: Antibody response to mRNA SARS‐CoV‐2 vaccination in 182 patients after allogeneic hematopoietic cell transplantation date: 2022-04-18 journal: Transpl Infect Dis DOI: 10.1111/tid.13828 sha: a8bdbfbff2becd2579ce748409d3a50c5f3fe300 doc_id: 702549 cord_uid: rznlagol INTRODUCTION: Patients after allogeneic stem cell transplantation are at high risk for infection‐related complications, and vaccination efficacy might be impaired depending on the immune reconstitution. In this study, we evaluate their response to mRNA vaccines against SARS‐CoV‐2. METHODS: During routine follow‐up visits, patients were asked about their vaccination status and if they had a previous infection with SARS‐CoV‐2. In fully vaccinated patients, the antibody titer was measured using the Roche Elecsys Anti‐SARS‐CoV‐2 S test. A titer of <1 U/L was considered as negative, titers of ≥250 U/ml as a high antibody titer, and a titer of 50–249 U/ml as a low antibody titer. Patient characteristics were evaluated by chart review to identify risk factors for poor vaccination response. RESULTS: The majority of patients developed a high antibody titer (138 out 182 patients, 75.8%). Risk factors for a low antibody titer were immunosuppressive therapy, a lymphocyte count <0.9 G/L, ongoing treatment for the underlying malignancy, and active graft‐versus‐host disease (GvHD). Donor type, underlying disease, a previous SARS‐CoV‐2 infection, and sex did not significantly influence the response to the vaccination. DISCUSSION: While patients undergoing allogeneic stem cell transplantation have been excluded from the initial registration trials, our real‐world experience with a large patient cohort confirms the data of previous studies, showing that most patients do have a good response to mRNA vaccines against SARS‐CoV‐2. Nevertheless, a significant proportion of patients shows an inadequate vaccination, which can be improved after a third vaccination in most cases despite immunosuppressive therapy. The Only patients who consented to the general research were assessed and data were anonymized after finishing the data collection process. One hundred eighty-two patients with antibody measurements between March 23 and September 1, 2021 were included. Immunosuppressive therapy as well as maintenance or preemptive therapy for underlying malignancy were recorded and graft-versushost disease (GvHD) was documented. Patients were considered to have an immunosuppressive therapy if they had one or more of the Antibody titers were measured using the Elecsys Anti-SARS-CoV-2 Spike assay on the cobas e801 platform (Roche, Rotkreuz, Switzerland) as part of the routine laboratory tests performed on site in the laboratory of the University Hospital Basel. 4 Titers of <1.0 U/ml were considered as negative, a titer of 1-249 U/ml as a low antibody, and titers of ≥250 U/ml as a high antibody titer. By dilution, a maximum titer of 2500 U/ml could be measured, values above were given as >2500 U/ml and were assumed to be 2500 U/ml for the statistical analyses. For those patients with a third vaccination because of an insufficient antibody titer (negative or low), a further antibody titer measurement was recommended to assess response and data were collected by chart review. Statistical analyses were performed using SPSS. Statistical significance was evaluated with chi-square test and a p-value <.05 was considered as statistically significant. Antibody titers were measured in 182 patients with a median age of 56 years (range 21-80 years) ( Imdevimab as well as Remdesivir. Expectedly, the antibody titer was >2500 U/L thereafter. Rebuilding protective immunity is of paramount importance for patients after allogeneic HCT. Several reports showed that SARS-CoV-2 vaccination is significantly less effective in patients after allogeneic HCT compared to the general population, 5-13 reporting seroconversion in 68%-83%. As the vaccination is safe and feasible, it remains a pivotal part in preventing COVID-19 in this vulnerable patient population. Some reports [6] [7] [8] include only patients vaccinated with BNT162b2 (BioNTech Pfizer), including two prospective trials, 12, 13 while others 5, [9] [10] [11] include results after vaccination with BNT162b2 or mRNA-1273 (Moderna). In our patients, we found a response to vaccination with either BNT162b2 or mRNA-1273 in 92% of patients, with high titers in 75% ( Figure 1 ). The rate of any antibody response is slightly higher than previously reported and might be partially explained by the higher median interval between HCT and vaccination of 39 months compared with roughly 2 years in other studies. 6, 8, 10, 11 We can confirm the findings of other reports 6,7,10,11 that time interval less than 1 year between HCT and vaccination is a risk factor for an insufficient antibody response, while others have not. 9 Our study has some limitation. Due to the retrospective study design, the time interval between last vaccination and antibody assessment was not standardized. Although there was no significant difference in antibody levels between patients assessed within less than 60 days versus longer time intervals, we cannot exclude the patients in the latter group might had different characteristics, allowing longer intervals between visits. Furthermore, it was not possible to collect data on mild side effects or mild transient manifestations of GvHD. However, both a careful interim history as well as a systematic assessment for signs and symptoms of GvHD are part of every follow-up visit so that both serious side effects and new or aggravating GvHD manifestations would have been noted. Finally, we cannot exclude asymptomatic infections as an additional reason for measurable antibody levels without baseline serology, but we believe that due to the high awareness of the symptoms and a low threshold for testing among patients and closely associated persons, the rate of oligo-or asymptomatic infections are likely low. Of note, this study was done before appearance of the SARS-CoV-2 Omicron variant In conclusion, mRNA vaccination shows a favorable risk profile in recipients of allogeneic HCT. 12, 13 In contrast to other post-transplant vaccinations that are usually performed at the transplant center, all patients were vaccinated by community-operated vaccination centers in the catchment area, making it more challenging for a transplant team to assess response to vaccination. Response rate is high in patients without pharmacological immunosuppression, lymphopenia, or active antitumor therapy, especially when the patient is more than 1 year after transplant. mRNA-1273 seems slightly more immunogenic than BNT162b2. However, measurement of antibody response is recommended in all patients to confirm successful seroconversion, which is successful in a significant proportion of patients. 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The authors declare that there is no conflict of interest.