Antibody Response After Initial Vaccination for SARS-CoV-2 in Patients With Amyloidosis

Abstract

In systemic amyloidoses, misfolded proteins form amyloid fibrils that are deposited in various tissues causing organ dysfunction. In systemic immunoglobulin light chain (AL) amyloidosis, a usually small plasma cell clone produces a monoclonal immunoglobulin light chain with amyloidogenic properties. Although modest in size, this plasma cell clone may affect immunocompetence, while organ dysfunction further increases susceptibility and risk of complications of infectious diseases. In addition, the use of anti-plasma cell therapies further decreases the fitness of the immune system. In other types of amyloidosis, most common being transthyretin-related amyloidosis (ATTR), this immunosuppressive effect may not be present but other factors related to organ dysfunction may affect the fitness of the immune system. Thus, COVID-19 is particularly challenging for patients with critical organ involvement by amyloidosis.1,2 Vaccination against SARS-CoV-2 is the best strategy to avoid severe COVID-19, however, response to vaccines may be compromised in patients with plasma cell malignancies or other B-cell lymphoproliferative disorders.3,4 In patients with ATTR such a clone does not exist, but other factors could affect response to vaccination. Since it is clinically relevant to evaluate the efficacy of anti-SARS-CoV-2 vaccination in patients with AL and ATTR amyloidosis, to optimize strategies for the immunization of this vulnerable patient population, we measured the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 after the first dose of the BNT162b2 and AZD1222 vaccines. This report is part of larger prospective study (NCT04743388) for the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination. The major inclusion criteria for this analysis include: (1) a prior diagnosis of AL or ATTR amyloidosis; (2) eligibility for vaccination. As a control group we used volunteers matched for age, gender (1:3) who had (1) no autoimmune or active malignant disease; (2) no HIV or active hepatitis B and C infection. Serum was separated within 4 hours from blood collection and stored at −80°C until the day of measurement on (1) day 1 (D1; before the first dose of BNT162b2 or AZD1222) and (2) day 22 (D22; before the second dose of the BNT162b2 or 3 weeks after the first dose of AZD1222). NAbs against SARS-CoV-2 were measured using FDA-approved methodology (ELISA, cPass SARS-CoV-2 NAbs Detection Kit; GenScript, Piscataway, NJ).5 The study was approved by the respective Ethical Committees in accordance with the Declaration of Helsinki and all patients and controls provided written informed consent before enrollment. Our study included 59 patients with AL amyloidosis (34 males/25 females; median age: 62, interquartile range [IQR]: 57– 72 years) and 118 controls (68 males/50 females; median age: 62, IQR: 57–72 years), who were vaccinated during the same period, at Alexandra Hospital, Athens, Greece. The patients followed a centrally controlled vaccination program run by the Greek healthcare authorities that prioritized healthcare workers, the elderly and patients with malignancies for anti-SARS-CoV-2 vaccination (with either BNT162b2 or AZD1222). The proportion of the different vaccines was similar in patient and control groups (78% had BNT162b2 and 22% had AZD1222, respectively). At the time of vaccination, 31/59 (53%) patients were receiving anti-clonal therapy. Table 1 shows the other characteristics of the patients.