Immunogenicity and safety of SARS-CoV-2 mRNA vaccine in patients with nephrotic syndrome receiving immunosuppressive agents

Abstract

Background: As there are no large-scale reports of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with nephrotic syndrome using immunosuppressive agents, we conducted the prospective study.

Methods: SARS-CoV-2 mRNA vaccines were administered to patients with nephrotic syndrome receiving immunosuppressive agents. The titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. We evaluated factors associated with antibody titers after vaccination and analyzed adverse events.

Results: We enrolled 40 patients and evaluated vaccine immunogenicity in 35 of them. Seroconversion (> 0.8 U/mL) was achieved in all patients, and the median antibody titer was 598 U/mL (interquartile range, 89-1380 U/mL). Patients using mycophenolate mofetil (MMF) showed lower antibody titers than those who were not (median: 272 U/mL vs. 2660 U/mL, p = 0.0002), and serum immunoglobulin G (IgG) levels showed a weak linear relationship with antibody titers (R² = 0.16). No breakthrough infections were noted. Three patients (7.5%) suffered from a relapse of nephrotic syndrome (2 and 3 days, respectively, after the first dose and 8 days after the second dose), two of whom had a history of relapse within 6 months before the vaccination.

Conclusions: The SARS-CoV-2 mRNA vaccine was immunogenic in patients with nephrotic syndrome using immunosuppressive agents, although the use of MMF and low levels of serum IgG were associated with lower antibody titers after vaccination. Patients with high disease activity may experience a relapse of nephrotic syndrome after vaccination. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Mycophenolate mofetil; Nephrotic syndrome; Relapse; SARS-CoV-2 S antibody; Seroconversion; Serum IgG.

Fig. 1

CONSORT flow diagram of the study population

Fig. 2

SARS-CoV-2 S antibody titers after vaccination (n = 35). Box represents the median and interquartile range (IQR). Median: 598 U/mL, IQR: 89–1380 U/mL, minimum: 5 U/mL; maximum: 6520 U/mL

Fig. 3

Factors associated with SARS-CoV-2 S antibody titers after vaccination. a Comparison between patients using or not using MMF. b Relationship between serum IgG levels and SARS-CoV-2 S antibody titers (SARS-CoV-2 S antibody = 1.65 × IgG − 524.2, R² = 0.16). c Relationship between PHA-SI and SARS-CoV-2 S antibody titers (SARS-CoV-2 S antibody =  − 0.75 × PHA-SI + 1234.0, R.² = 0.003). Data in all panels are expressed as median (IQR). SARS-CoV-2 S antibody, severe acute respiratory syndrome coronavirus type 2 spike protein receptor–binding domain antibody; MMF, mycophenolate mofetil; IgG, immunoglobulin G; PHA-SI, phytohemagglutinin-stimulation index