In Austria, the first cases of the current pandemic of coronavirus disease (COVID-19) appeared on February 25^th, 2020 when two individuals tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). As of November 7^th 2021, 883887 SARS-CoV-2 cases and 11502 deaths due to COVID-19 were documented in Austria (population size 8.9 million) (2). Among the first vaccines available against SARS-CoV-2, the lipid-nanoparticle-encapsulated mRNA-based vaccines mRNA-1273 and BNT162b2 proved to be safe and induce high levels of protection against COVID-19 in the general population (3, 4). Furthermore, it was shown that mRNA vaccines elicit serum neutralizing activity against wild-type SARS-CoV-2 and various emerging mutants (5). Dialysis patients are among the most vulnerable individuals susceptible to COVID-19, having a reported 28-day case-fatality rate up to 25% after infection with SARS-CoV-2 due to age and frailty (6). Furthermore, it is known that dialysis patients in general are immunocompromised and respond less effectively to many vaccines (7–10), although exceptions exist (11). In an effort to protect this vulnerable group, dialysis patients were recommended to be prioritized for vaccination against SARS-CoV-2 (12, 13).

According to the Austrian Dialysis and Transplantation Registry (ÖDTR) the mRNA-1273 vaccine was used in 52.5% of hemodialysis (HD) patients and 75.6% of peritoneal dialysis (PD) patients. The BNT162b2 vaccine was used in 46.6% of HD patients and 23.6% of PD patients, respectively (14).

Since the beginning of 2021, several studies in hemodialysis patients have reported varying seroconversion rates in mRNA vaccinated patients that range from 18% to 53% after one dose and from 70% to 96% after two doses, respectively (15). The humoral response to SARS-CoV-2 vaccination may differ between HD and PD patients (16). However, the majority of trials investigated these early antibody responses to anti-SARS-CoV-2 vaccines in patients on hemodialysis and only a few focused on peritoneal dialysis (17).

In this retrospective observational study, we report on 39 PD patients at our institution who received two doses of the mRNA-1273 anti-SARS-CoV-2 vaccine. We analyzed how many percent of these patients seroconverted after one or two vaccine doses and looked at tolerability of the vaccine in this patient population. Furthermore, we looked at antibody response after the first and second dose and analyzed factors which might be associated with anti-SARS-CoV-2 S antibody titers.

In total 40 PD patients received two doses of the Moderna^®mRNA-1273 vaccine. One of these patients was excluded since he was retrospectively tested positive for antibodies targeting the nucleocapsid (N) antigen, confirming previous (asymptomatic) COVID-19 infection. The study cohort consisted of 26 men and 13 women. The mean age was 55.2 years (range 29-80 years) with a median dialysis vintage of 16.1 months (IQR 6-31.3 months). Seven of 39 patients received immunosuppressive therapy. Detailed characteristics of the study cohort are shown in Table 1 .

In this study we showed that 38 of 39 PD patients at our institution responded well to two doses of the anti-SARS-CoV-2 mRNA-1273 vaccine, reaching a seroconversion rate of 97.4%. The majority of the studies on humoral response to mRNA-based anti-SARS-CoV-2 vaccines included patients on hemodialysis. The seroconversion rates found in COVID-19 naive HD patients using predominantly the BNT162b2 vaccine were below 43% after a single dose of vaccination and between 82-97% after two doses (16, 23–42). Only three studies reported lower seroconversion rates (71-73%) in HD patients (36, 43, 44). Kaiser et al. described in a non-randomized retrospective study including 116 HD patients, that patients vaccinated with mRNA-1273 developed higher antibody titers than those that received BNT162b2 (32), whereas Broseta et al. reported similar seroconversion rates (45).

Few studies investigated the immune response of PD patients after SARS-CoV-2 vaccination, using predominantly the BNT162b2 vaccine (16, 23, 34, 39). These studies described seroconversion rates after the second dose between 85% and 100%, which are comparable with those found in the present study. In the only study analyzing the humoral response of PD patients to mRNA-1273 vaccine, published by Rodriguez-Espinosa, the seroconversion rate after two vaccine doses (97%) was similar to our results (97.4%) (46). However, in our study the percentage of patients with detectable humoral response after the first dose was higher than the one found by Rodriguez-Espinosa (86.4% vs 62.5%). Younger age (mean 55.2 vs 62.2 years) and shorter dialysis vintage (mean 22.5 vs 64.5 months) of our cohort could explain the higher seroconversion rate after one dose of vaccine observed in our PD patients.

Rodriguez-Espinosa et al. could not find any factors associated with the antibody response to the mRNA-1273 vaccine in PD patients (46). In an observational study including 21 PD and 35 HD patients, Tylicki et al. suggested that younger age, shorter dialysis vintage, better residual renal function and fewer co-morbidities of PD patients lead to a higher antibody response after vaccination with the BNT162b2 vaccine in the PD cohort (16). In accordance with this hypothesis we found in the univariate analysis that shorter dialysis vintage and a lower Davies Comorbidity Score were associated with higher antibody titers after the first vaccine dose. Other studies reported that younger age (23, 39) and higher serum albumin (23) were factors that correlated with higher antibody levels in response to BNT162b2 vaccine in PD patients. Since both studies did not report the characteristics of included PD patients, any comparison with our population was unfeasible. In the multivariate analysis none of the factors (age, gender, immunosuppressive therapy, sodium, albumin, CRP, dialysis vintage, BMI, Kt/V, GFR and Davies Comorbidity Score) had a significant effect on the antibody titers in our PD cohort, possibly due to the limited number of included patients. However, we were able to observe some trends. Men tended to have lower antibody titers. Higher GFR and younger age seemed to be associated with higher antibody titers, confirming previous data with the BNT162b2 vaccine (16, 23, 39).

An important factor that interferes with the humoral response to the SARS-CoV-2 vaccines appears to be the immunosuppressive therapy of kidney transplant and dialysis patients (34, 47–49). We showed that among patients with immunosuppressive therapy, those who were treated with MMF had a lower anti-SARS-CoV-2-S antibody response compared to the patients treated with prednisolon. MMF, a potent inhibitor of both T- and B- lymphocyte proliferation, is broadly used as immunosuppressive drug in transplant patients (50). In agreement with our findings, recently published data described a MMF-dose dependent reduction of humoral response after SARS-Cov-2 vaccination in kidney transplanted patients (47–49). Furthermore, MMF was associated with a significantly reduced BNT162b2-induced immunogenicity in patients with autoimmune inflammatory rheumatic diseases ( 51). These observations raise the question whether interrupting or reducing MMF dose before vaccination might improve the humoral response.

To our knowledge this is the first study describing the local and systemic adverse events in PD patients after the first and the second mRNA-1273 vaccination. The percentage of PD patients reporting AEs at the site of injection was lower than in the general population receiving the same vaccine: (79.5% vs. 84.3% after the first dose and 79.5% vs. 88.6% after the second dose, respectively) (3). As for the general population, the most common local AE was pain at the injection site. The occurrence of systemic AEs in our patients was less frequent in comparison to the general population (38.5% vs. 54.9% after the first dose and 51.3% vs. 79.4% after the second dose, respectively). These results could be explained by the fact that our study cohort consisted of 66.7% male participants compared to the 52.7% reported by Baden et al. Other studies have reported that women show a higher rate of adverse events in response to mRNA vaccines (52). Furthermore, the incidence of local and systemic adverse events in our study population was higher than in HD patients receiving the BNT162b2 vaccine (42, 52). The fact that our study participants were treated with PD, were on average 13 years younger than the participants of the other studies and received a different vaccine may explain these differences. A negative correlation between age and number of adverse events in response to mRNA vaccines has been reported previously (4, 42). Accordingly, systemic AEs in our study were more common in younger patients (87% of the patients reporting systemic AEs were younger than 65 years old). Furthermore, the severity of AEs increased after the second dose of vaccine, in consistency with data published by Baden et al. in the general population (3).

Our study had certain limitations. Most importantly, interpretation of our data may be limited by the fairly small sample size. Other limitations include the retrospective single center design and lack of a control group. However, our data on the safety of the mRNA-1273 vaccine in PD patients represent an asset to the current knowledge, since, so far, safety data using this type of vaccine have not been reported in this patient group. The fact that the majority of adverse events were mild and no serious AEs occurred, might be helpful for PD patients to overcome their skepticism towards SARS-CoV-2 vaccination.

In conclusion, we found a high seroconversion rate of 97.4% and high median antibody titer levels in this cohort of PD patients after vaccination with two doses of mRNA-1273. Lower Davies Comorbidity Score and shorter dialysis vintage were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose. The two dose vaccination scheme was tolerated well and did not cause any serious AEs in this population.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Committee of the Medical University of Vienna EK 1418/2021. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

GB: contributed to conception and design of the study, analyzed data and wrote the manuscript. RM: analyzed data and wrote sections of the manuscript. FF: contributed to the design of the study and performed the statistical analysis. MG: contributed to conception and design of the study RS: performed antibody titer measurements. AV: contributed to conception and design of the study and wrote the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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