Dialysis patients are at increased risk of severe coronavirus disease 2019 (COVID-19) infections [1]. Although these patients are obviously a high priority for vaccination, there are some concerns concerning the efficacy of vaccines. Indeed, dialysis patients are considered to be less prone to respond to vaccines [2]. However, few data exist concerning humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with BNT162b2 (Pfizer-BioNTech) in patients on haemodialysis (HD). However, about 90% of HD patients exhibit antibody positivity after two injections of vaccine [3–5]. Nevertheless, factors associated with poor response are not well described.
We studied 50 HD patients who were COVID-19 naïve (no clinical history, negative serology) and 15 HD patients with a history of COVID-19 infections. All the patients received two doses of the BNT162b2 mRNA COVID-19 vaccine. Humoral response (SARS-CoV-2 immunoassay, Abbott®) and factors associated with this response were studied. As a relevant threshold cannot be determined, we used that provided by the manufacturer and a more empirical defined by a value above the first quartile of results (224 UA/mL).
Among naïve patients, 45 (90%) had an antibody titre >50 UA/mL and 37 (74%) >224 UA/mL (threshold of the first quartile) 1 month after the second dose. All non-responder patients were or have been under immunosuppressive drugs (titre <50 UA/mL). Considering a threshold of 224 UA/mL, a present or past history of immunosuppressive drugs was more frequent in non-responder patients (54% versus 23%; P = 0.007). Non-responder patients had higher C reactive protein (CRP) concentrations (13.6 ± 9.3 versus 5.7 ± 3.9 mg/L; P = 0.016) and lower lymphocyte count (1046 ± 301 versus 1363 ± 316/mm2; P = 0.031). There was a close inverse relationship between CRP concentration and antibody level (r = −0.26; P = 0.021). Other clinical and biological parameters were similar in responders and non-responders (Table 1).
Table 1.
Clinical and biological characteristics of responders and non-responders patients (threshold 224 UA/mL)
| Non- responders | Responders | P | |
|---|---|---|---|
| Age (years) | 75 ± 10 | 69 ± 10 | 0.185 |
| Gender (% male) | 62 | 59 | 0.895 |
| Dialysis vintage (months) | 24 ± 21 | 31 ± 23 | 0.145 |
| Use of immunosuppressive drugs (%)* | 54 | 23 | 0.007 |
| Albumin (g/L) | 31 ± 4.9 | 32 ± 3.3 | 0.438 |
| CRP (mg/L) | 13.6 ± 9.3 | 5.7 ± 3.9 | 0.016 |
| Haemoglobin (g/100 mL) | 11.2 ± 1.5 | 11.6 ± 1.8 | 0.156 |
| Lymphocytes count (/mm3) | 1046 ± 301 | 1363 ± 316 | 0.031 |
Data are presented as mean ± standard deviation, or %. *Concerning immunosuppressive drugs: in non-responders—rituximab, 2; cyclophosphamide, 2; melphalan, 1: on going. Calcineurin inhibitors, 2: stopped (24 and 31 months ago). In responders—calcineurin inhibitors, 5 (with mycophenolic acid in 2); mTOR inhibitors, 1; azathioprine, 1: all stopped (mean time since withdrawal: 36 ± 29 months).
Among previously exposed HD patients, we observed a stronger response to vaccine than that in naïve patients [5516 (895–40 000) versus 1837 (0–7459) UA/mL; P < 0.001).
We report in a single-centre study that 90% of dialysis patients have a vaccine response after two doses of BNT162b2 mRNA COVID-19 vaccine. We observe that the immune status markedly affects the vaccination response.
The dialysis population is heterogeneous. In this study, 30% of patients received or had received immunosuppressive drugs. Optimal response to vaccination in this group was only 53%, whereas it was 85% in those who did not take immunosuppressive drugs. Of note, a reduced response to BNT162b2 mRNA COVID-19 vaccine has been already reported in kidney transplant patients [6]. Exposure to such medications seems to be an important point to consider in the vaccination strategy.
HD patients exhibit both immune deficiency, which is similar to accelerated immune senescence, and inflammation, which is in part related to chronic innate immune activation [7, 8]. The term ‘inflammaging’ is frequently proposed to include these two aspects. We report that inflammaging characterized by low lymphocyte count and elevated CRP levels is associated with a decreased humoral response to the BNT162b2 mRNA COVID-19 vaccine. More accurate determination of the individual immune profile is required to better define vaccination protocol in dialysis patients.
Surprisingly, age was not associated with vaccination response. This may be explained by the low proportion of young patients. However, very old patients seem to have a similar response to patients in age range 50–70 years.
Patients with a history of COVID-19 infection have an explosive reaction after two doses of BNT162b2 mRNA COVID-19 vaccine. A single injection could be considered in these patients.
Two doses of BNT162b2 mRNA COVID-19 vaccine provide a strong humoral response in three-quarters of dialysis patients. The individual immune status seems to be more important to consider than the status of dialysed persons.
CONFLICT OF INTEREST STATEMENT
None declared.
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