Introduction

COVID-19 infection in kidney failure patients receiving dialysis has been reported to have high morbidity and mortality. [1, 2] Hospitalization of dialysis patients for COVID-19 infection not only utilizes hospital isolation beds, and dialysis facilities but also increases the workload of inpatient dialysis nurses. Therefore, prevention of COVID-19 infection by applying strategies to minimize the risk of infection among kidney failure patients receiving dialysis [3,4,5,6] is of paramount importance to reduce morbidity, mortality, and healthcare cost.

Peritoneal dialysis (PD) patients are vulnerable to COVID-19 infection due to their immunocompromised state and are at increased risk of develo** serious complications if they contract the virus. In a case series of 11 PD patients with COVID-19 infection, 3 required mechanical ventilation, and 2 died. [7] Therefore, in addition to the practice of preventive strategies for COVID-19 infection, such as wearing a face mask, social distancing, and hand hygiene, immunization against severe acute respiratory syndrome coronavirus 2 (SAR-COV-2) is recommended to mitigate the risk of infection and its associated complications in PD patients. The safety of the SAR-COV-2 vaccine has been tested in the general population and kidney failure patients, [8,9,10,11] particularly in hemodialysis patients, however, there is a paucity of studies available on the adverse effects of SAR-COV-2 vaccine among PD patients. There was a previous report of adverse effects of the COVID-19 vaccine among 32 PD patients, [12] however, the study was limited by small sample size. The present cross-sectional study, using online self-administered survey questionnaires, aimed to provide information on the local and systemic adverse effects of the COVID-19 vaccine experienced by PD patients, factors associated with adverse effects, source of vaccine information for PD patients, and reasons for delay or rejection of the vaccine.

Materials and methods

This was a single-center, cross-sectional study conducted between the period of October 2021 to November 2021. The study included PD patients who were followed up at Singapore General Hospital (SGH). The study has obtained approval from the local Ethics Committee, Singapore Health Service (SingHealth) Centralized Review Institutional Board (CRIB), reference number 2021/2563.

The study included anonymized data from patients, and the survey was conducted using the secured online survey platform; form.sg platform. PD patients who were followed up in the center were provided with a survey link or barcode to assess the survey. The survey questions were available in English Language only. Data collected for the survey included age, gender, race, marital status, employment status, education status, first modality of kidney replacement therapy (KRT), modality of PD, duration of PD, and self-care or assisted PD. The other data collected in the study included a source of information regarding the vaccine. COVID-19 vaccination record, types of vaccine, reasons for or against the COVID-19 vaccine, adverse effects of vaccine (local and systemic effects) for each dose of vaccine, hospitalization for vaccine-related adverse effects, history of COVID-19 infection, history of immunization with influenza vaccine, and history of drug allergy. Survey questions related to adverse effects, source of vaccine information, and reasons for or against the vaccine, were presented as multiple-choice questions, and participants were allowed to choose more than one answers that applied to them, and also a free text for them to include additional response.

The primary outcome was vaccine-related adverse effects experienced by PD patients. Secondary outcomes were sources of information for the vaccine, reasons to receive or decline the vaccine, and factors associated with the development of adverse effects of the vaccine. Data were presented as frequency (percentage) for the primary outcome and some secondary outcomes. Factors associated with vaccine adverse effects for first and second doses of vaccine were analyzed using logistic regression. Variables examined included age group (> 65 versus ≤ 65 years), gender, race (Chinese versus non-Chinese), employment status (full/part-time versus not employed/retired), presence of drug allergy, types of vaccine (Pfizer versus Moderna), and history of receiving influenza vaccine. Variables with a p < 0.2 in univariate analysis were included in the final analysis. P < 0.05 were considered statistically significant. Data were analyzed with Stata (version 14.0 Stata Corp LP).

Results

A total of 107 PD patients responded to the survey for the COVID-19 vaccine between October and November 2021. Of these, 102 (95%) patients reported receiving vaccines: 23 patients (22%) received 3 doses, 78 patients (77%) received 2 doses and 1 patient (1%) received 1 dose of COVID-19 vaccine (Supplemental Table 1). The majority of patients (91%) received the mRNA (Pfizer) vaccine and few received Moderna (8%) or Sinovac (1%) vaccines. The demographic data of the study participants are presented in Table 1; 50% were male, 79% Chinese ethnic, and most of them performed PD therapy themselves. Four patients developed vaccine breakthrough infection and all recovered at home without requiring hospitalization.

Table 1 Demographic data of study participants
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Local and systemic adverse effects

No severe adverse effects were observed with the SAR-COV-2 vaccine in PD patients. After the first dose of COVID-19 vaccines, 75% did not suffer any adverse effects of the vaccine, whilst 25% reported having one or more local and systemic adverse effects of the vaccine (Figs. 1 and 2). The common local adverse effect was pain at the injection site (20.6%), and the common systemic adverse effects were muscle pain (14.7%) and fatigue (12.7%). Most patients (72%) did not experience any local or systemic adverse effects, whilst 29 patients (28%) experienced one or more local or systemic adverse effects after the second dose of the vaccine. The common local and systemic effects were similar to those after the first dose such as pain at the injection site (21.6%), fatigue (18.6%), muscle pain (14.7%), and fever (14.7%), respectively (Figs. 1 and 2). Among 23 PD patients who received the third dose, 10 patients reported having at least one local or systemic adverse effect with the vaccine. The common adverse effects were similar including pain at injection, fatigue, muscle pain, or fever (Figs. 1 and 2). Among all PD patients who received the vaccine, none of them required hospitalization for vaccine-related adverse effects. Individuals who did not develop adverse effects with the first dose were significantly less likely to experience adverse effects with subsequent doses of the vaccine. Approximately 86% of patients who had no adverse effects with the first dose did not experience any adverse effects with the second dose of the vaccine. Similarly, 80% of patients experiencing adverse effects with the third dose of vaccine had previous adverse effects with the second dose of vaccine.

Fig. 1
figure 1

Local adverse effects reported by study participants after COVID-19 vaccination

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Fig. 2
figure 2

Systemic adverse effects reported by the study participants after COVID-19 vaccination

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The subgroup analyses were performed to examine risk factors associated with adverse effects of the vaccine. Age, race, employment status, and history of drug allergy or history of receiving influenza vaccine were not significantly associated with the development of adverse effects of the COVID-19 vaccine (Table 2). However, gender (female) was significantly associated with a higher risk of develo** local or systemic adverse effects (odds ratio: 3.37; 95% confidence interval (CI) 1.25 – 9.08; p = 0.02) with first dose COVID-19 vaccine (Table 3). The association between gender and adverse effects was not observed in the second dose of the vaccine.

Table 2 Univariate logistic regression of risk of develo** adverse effects with COVID-19 vaccination
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Table 3 Multivariate logistic regression of risk of develo** adverse effects with COVID-19 vaccination
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Information for COVID-19 vaccine

Sources of information for the COVID-19 vaccine were explored during the survey and 107 participants completed the survey, indicating that the common sources of information for the COVID-19 vaccine were government (48%), followed by family members (36%), and media (television or newspaper) (32%) (Fig. 3).

Fig. 3
figure 3

Sources of information for COVID-19 vaccine

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Reasons for receiving or refusal or delay in receiving COVID-19 vaccine

Reasons for receiving the vaccine were examined among participants (n = 102) who received at least one dose of the vaccine. The common reasons to receive the vaccine were perception of the seriousness of COVID-19 infection (63%), followed by a recommendation by the government (46%), and recommendation by doctors (36%) (Fig. 4). Reasons for refusal or delay in receiving the vaccine were explored among participants (n = 5) who have not received the vaccine during the study, the main reason for vaccine hesitancy was concern about the safety of the vaccine (60%).

Fig. 4
figure 4

Sources of information for COVID-19 vaccine

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Discussion

The study demonstrated that the majority of PD patients did not experience any adverse effects of COVID-19 vaccination. The common local adverse effect of the vaccine was pain at the injection site, and common systemic adverse effects were muscle pain, fatigue, or fever. None of them required hospitalization for vaccine-related adverse effects. The female gender was associated with a higher risk of develo** adverse effects than the male gender after the first dose of the vaccine but such association was not observed in the subsequent dose. Most patients reported that the main source of vaccine information was the government. The main reason for receiving the vaccine for PD patients was the perception of the seriousness of COVID-19 infection and the main reason for vaccine hesitancy was a concern for the safety of the vaccine.

In a previous study, it has been reported that physician recommendations influenced vaccine uptake among dialysis patients. [13] In the present study, approximately one-third of participants indicated that physicians’ recommendations encouraged them to receive the vaccine. Given that PD patients are usually followed up by physicians at PD clinic, the vaccination status should be included as a part of the routine checklist for the PD program.

Most participants in the study received the mRNA (Pfizer) vaccine, which has 95% vaccine efficacy. [11] In the present study, 4 PD patients developed vaccine breakthrough COVID-19 infection but none of them required hospitalization and recovered at home. Vaccination has been shown to minimize the severity of infection in the general population. [14, 15] In a previous study of influenza vaccine in PD patients, vaccinated individuals were significantly associated with reduced morbidities and mortality. [16] Association between vaccination and outcomes of COVID-19 infection among PD patients should be examined in future studies.

In the present survey, only 5% of participants have not received a vaccine, which was largely due to concern about vaccine safety. A previous survey of beliefs and attitudes towards the COVID-19 vaccine among maintenance dialysis patients (mainly HD patients) reported a similar reason for vaccine hesitancy. [17, 18] Therefore, the study on the safety profile of vaccines on patients receiving dialysis would potentially encourage vaccine uptake among dialysis patients. Unfortunately, there was a paucity of data on the adverse effects of the SARS-CoV-2 vaccine among the PD population.

A previous large randomized control trial (RCT) on the efficacy and safety of the COVID-19 vaccine in the general population (n = 43,448) reported that the adverse effects of the vaccine were 27%. [11] Similarly, in the present study, the adverse effects of the vaccine were 25% and 27% after the first and second dose of the vaccine, respectively. Only a few patients have received the third dose during the time of the survey and therefore, caution should be exercised in the interpretation of the proportion of patients who developed adverse effects with the third dose. A previous RCT of safety and efficacy of the vaccine in 30,420 individuals reported that pain at the injection site was the most common local adverse effect of the vaccine. [8] A previous small study of COVID-19 vaccine tolerability in 28 PD patients reported having mild adverse effects, such as pain at the injection site (36%). [12] Similarly, in the present study, the main local side effect of the vaccine was pain at the injection site.

A study of COVID-19 vaccine safety among solid organ transplant recipients also reported female individuals had a higher risk of develo** systemic adverse effects than male individuals. [19] Similarly, the present study also demonstrated that the female gender was associated with a higher risk of develo** adverse effects after the first dose of the vaccine. The reason for such association is unclear, but gender was no longer associated with vaccine adverse effects in the subsequent doses of the vaccine.

To date, this is one of few studies of SARS-COV-2 vaccine adverse effects on the PD population. The study also explored the source of information for vaccines and the reasons for PD patients receive or reject vaccination. However, the study suffers from several limitations including a single-center study, cross-sectional study design, and using the online survey platform, which might potentially exclude those patients who were not equipped with technology to use the online survey. In addition, the survey was conducted in the English language only, therefore, excluding those patients who are illiterate or have a language barrier. Moreover, there is a possibility of recall bias and selection bias due to the study design. Moreover, the majority of patients received a particular type of vaccine (Pfizer), therefore, findings from the study may not be generalizable to other types of vaccines. Nonetheless, with a paucity of available data on the adverse effects of vaccines experienced by PD patients, the findings from the present study would potentially encourage more PD patients to receive the vaccine.

In summary, the SARS-COV-2 vaccine was generally safe for PD patients and a minority of them developed mild local and systemic adverse effects, which were commonly observed with other viral or influenza vaccines. None of them required admission for vaccine-related adverse effects. Most PD patients received vaccines because of the perception of the severity of COVID-19 infection, and also vaccine was recommended by the government and doctors. Among patients who have not received the vaccine, vaccine safety was the main concern. The government was the main source of information about the vaccine. Only 5% of patients developed vaccine breakthrough infection and they recovered without requiring hospitalization. This finding may need to be confirmed in a future large study. Finally, the findings generated from the study would help address the vaccine hesitancy among PD patients.