Immunogenicity and tolerability of COVID‐19 vaccination in peritoneal dialysis patients—A prospective observational cohort study

In peritoneal dialysis (PD) patients, information on the immunogenicity and tolerability of SARS‐CoV‐2 vaccination is still scarce. We compared the immunogenicity and tolerability of SARS‐CoV‐2 vaccination of PD patients with that of medical personnel.

Conclusions: SARS-CoV-2 vaccination in COVID-19-naïve PD patients appeared to induce a very high rate of seroconversion but a substantially lower rate of patients with a strong response compared with medical personnel. Vaccination appeared to be safe in the PD patients studied.

| INTRODUCTION
Dialysis patients are considered an immunocompromised patient group. They are at much higher risk of infection and have higher COVID-19-associated infection and mortality rates than the normal population. 1 The optimal vaccination strategy against SARS-CoV-2 in immunosuppressed patients, such as dialysis patients, is still unclear.
Importantly, rates of seroconversion after vaccination are often lower in this patient group than in the normal population. 2 To date, numerous studies in the normal population and more than 40 studies in hemodialysis patients have evaluated seroconversion rates after SARS-CoV-2 vaccination. However, the immunogenicity and tolerability of SARS-CoV-2 vaccination in peritoneal dialysis patients may differ from that in hemodialysis patients and the normal population.
To date, there is limited information on the immunogenicity and tolerability of the SARS-CoV-2 vaccination in peritoneal dialysis patients. 3 There is a particular lack of studies which include an internal control group. A condensed literature overview including details of studies involving SARS-CoV-2 vaccinated peritoneal dialysis patients is provided in Table S1.
In a prospective observational cohort study, we aimed to compare SARS-CoV-2 antibody-related immunogenicity and tolerability of vaccination in peritoneal dialysis patients with medical personnel.

| Design and setting
In a prospective observational cohort study, all peritoneal dialysis patients treated at renal care centers in Potsdam, Ludwigsfelde, and Rangsdorf, Germany, were eligible to participate between February and August 2021 to measure SARS-CoV-2 antibody levels and to obtain information on the tolerability of SARS-CoV-2 vaccination  Peritoneal dialysis patients as well as immunocompetent medical personnel, both COVID-19 naïve or with COVID-19 more than 3 months prior to study entry, were enrolled after providing written informed consent for study participation and were vaccinated as described.
Exclusion criteria for SARS-CoV-2 antibody measurement were lack of written informed consent or age <18 years. The study was approved by the Ethics Committee of the "Landesärztekammer Brandenburg," Germany (S9/(bB)/2021). This manuscript adheres to the "Strengthening the Reporting of Observational Studies in Epidemiology" guidelines. 4

| Definitions
History of COVID-19 was defined as previous PCR-positive . A positive response to SARS-CoV-2 vaccine ("seroconversion") was defined as SARS-CoV-2 spike IgG level ≥50 AU/ml, a moderate vaccine response as level ≥500 AU/ml, and a strong response ≥1000 AU/ml, the latter corresponding to the 25th percentile of SARS-CoV-2 spike IgG levels in the current study population 6 weeks after the second vaccination. Furthermore, SARS-CoV-2-spike-IgGlevels ≥1000 AU/ml of the assay used in the present study correspond to an ACE2-receptor-binding-inhibition capacity >30%, 5 a cut-off value that is consistent with the titer of this assay considered acceptable by the FDA for neutralizing SARS-CoV-2. 6,7 Patients with seroconversion were referred to as responders and those without seroconversion as non-responders.

| Endpoints
Primary endpoint was SARS-CoV-2 spike IgG levels 6 weeks after second dose of vaccine. Secondary endpoints were the proportion of patients or medical personnel with positive, moderate, or strong SARS-CoV-2 spike IgG response 6 weeks after second dose of vaccine, spike IgG and IgM levels before and after both vaccinations, the proportion of patients with local, systemic, or severe vaccination side effects, the latter defined as medication intake or medical presentation within the first week after SARS-CoV-2 first and second vaccination, and, the number of any side effects in affected participants.  to take medications or present to a physician to treat vaccination side effects. Medical personnel also completed these questionnaires as described above.

| Search, study selection, and data extraction of condensed literature overview
To identify studies regarding immunogenicity or tolerability of SARS-CoV-2 vaccines, we used the databases PubMed, Scopus, and Web of Science, independently of the publication type and status and without any limits imposed on the time periods covered. Furthermore, we regularly screened medical journals that were relevant for the subject matter of our review article, and conference abstracts; we also searched pre-publication platform medRxiv for non-peer-review studies. Reference lists of identified publications were screened for relevance.
Effective date of search: 12 August 2021.
Results: PubMed, Scopus, and Web of Science: N = 92; medRxiv: N = 196. Then, double publications were excluded and extracted data on peritoneal dialysis patients was summarized in Table S1 including information on reference, vaccine type, number of patients and controls, inclusion/exclusion of individuals with peritoneal dialysis and prior COVID-19, SARS-CoV-2 antibody assay and cut-off used, vaccine response rate and SARS-CoV-2 antibody levels, and side effects.   Tables S2-S4. There were no significant differences between non-responders and responders.   Table 1. SARS-CoV-2 spike IgG levels before and after first vaccination are shown in Figure 2A,B.

| Medical personnel characteristics
In both groups, SARS-CoV-2 spike IgG levels were low after first vaccination (Table 1, Figure 2B). In peritoneal patients, SARS-CoV-2 spike IgG levels increased 21-fold from first to second vaccination, and, in medical personnel, 32-fold.

| SARS-CoV-2-vaccine tolerability
Questionnaires on SARS-CoV-2-vaccine tolerability were available from 28 COVID-naïve peritoneal dialysis patients (Figure 1).  The findings of the present study are novel with respect to the graded magnitude of the SARS-CoV-2 IgG spike levels in response to COVID-19 vaccination in peritoneal dialysis patients compared with normal population. While seroconversion rates (spike IgG level >50 AU/ml) were similar in both groups in the present study, peritoneal dialysis patients showed lower immunogenicity as they were less likely to reach a higher spike IgG cut-off value (>1000 AU/ml) compared with medical personnel. This cut-off value was considered a likely indication of better protection against COVID-19. 6,7 In our study, a threefold higher spike IgG level was found in medical personnel compared with patients, whereas this ratio was 1.5 times higher in a recent report. 16 SARS-CoV-2 spike IgG levels of peritoneal dialysis patients observed in the present study appeared to be similar or higher compared with that recently reported in hemodialysis patients; however in these studies, immunogenicity of vaccines in normal population and tolerability of vaccination in peritoneal dialysis patients or normal population was not reported. [17][18][19][20] The results of the present study can be explained, at least in part, by the shorter time between the first and second vaccinations, the different spike IgG assays, and the SARS-CoV-2 vaccines used compared with the recent report. The results of the present study may have several implications.
Vaccine breakthroughs observed in the normal population can also be expected in dialysis patients. This may also be true for peritoneal dialysis patients, who are similarly likely to fail to respond to hepatitis B vaccination as hemodialysis patients. 9 The results of the present study demonstrate effective and safe immunization against COVID-19 in peritoneal dialysis patients and support the notion that COVID-