Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccination.

To the editor:

Coronavirus disease 2019 (COVID-19) vaccine is one of the most effective public health interventions to end the COVID-19 outbreak. There are insufficient data on the use of COVID-19 vaccines in patients with autoimmune disease, but vaccines appear to be safe, and experience from previous vaccine studies does not indicate an increased risk of relapse/recurrence. However, theoretically, unwanted immunologic events, such as autoimmunity, may be triggered by vaccines. We describe a patient with membranous nephropathy (MN) who stayed in remission for 8 years and experienced a relapse after vaccination with a purified inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus vaccine called CoronaVac (produced in China by Sinovac).

A 66-year-old female patient presented with lower-extremity edema 2 weeks after the first dose of Sinovac’s COVID-19 vaccine. She had been diagnosed with biopsy-proven primary MN 8 years earlier. At that time, secondary causes of MN, such as malignancy, infections, and drugs, were excluded, but anti–phospholipase A2 receptor (anti-PLA2R) antibody could not be tested because it was not available. She was treated with steroid, cyclosporine, and lisinopril 10 mg/d. Complete remission was achieved within 3 months, and all immunosuppressive treatments were discontinued at 6 months while lisinopril 10 mg/d was continued. Renal functions and urinary protein excretion remained in the normal range without immunosuppressive therapy for 8 years. Her medical history also showed hypertension for 1 year and diabetes mellitus and hyperlipidemia for 6 years. On admission, urea was 93 mg/dl, creatinine was 2.78 mg/dl, serum albumin was 2.6 g/dl, spot urine protein-to-creatinine ratio was 9.42 mg/mg, and anti-PLA2R antibody was positive (120.53 relative units/ml [<14, negative; >20, positive]). Secondary causes of MN, such as malignancy, infections, and drugs, were excluded. No diabetic retinopathy was noted. A diagnosis of MN relapse was established given the clinical symptoms and laboratory examination results.

To our knowledge, cases of nephrotic syndrome in MN form have been reported after influenza vaccination. , A case of minimal change disease with full-blown nephrotic sydrome and acute kidney injury 10 days after the Pfizer-BioNTech COVID-19 vaccination has also been reported. In addition to this case, we observed 2 patients who developed anti-PLA2R–positive MN after SARS-CoV-2 infection. Our observation suggests that the SARS-Cov-2 virus may cause a loss of tolerance to the PLA2R antigen. Consequently, close follow-up of patients with MN after SARS-CoV-2 vaccination is recommended. Further studies are needed to determine whether relapse of MN is specific for inactivated SARS-CoV-2 virus vaccination and to decipher the mechanisms of immune dysregulation in those patients.