GLUCOCORTICOIDS' TREATMENT IMPAIRS the MEDIUM-TERM IMMUNOGENIC RESPONSE to SARS-COV-2 MRNA VACCINES in SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

ABSTRACT

Background: Patients with rheumatic diseases are at an increased risk for community infections (1,2). There still exists lack of data regarding SARS-CoV-2 vaccines' efficacy in vulnerable collectives with a compromised immune system, either due to a chronic pathology or to therapies targeting an autoimmune disease (3). Objectives: To evaluate neutralizing antibodies (nAB) to SARS-CoV-2 vaccine after 3 to 5 months from administration in Systemic Lupus Erythematosus (SLE) patients, as a surrogate of sustained-immunological response. Methods: This cross-sectional study compared nAB titre of 39 SLE patients and 37 Healthy individuals with no previous SARS-CoV-2 infection, who had all received two doses of a mRNA SARS-CoV-2 vaccine within the last 3 to 6 months. SLE patients included 10 Not-treated subjects, 10 patients with Hydroxychloroquine (First-Line), 10 subjects with immunosuppressive drugs (Second-Line) and 9 patients under biological treatment (Third-Line). Glucocorticoids were permitted in all patient groups. Neutralization assay were used to determine nAB titre according previously validated protocol (4). Results: Neutralizing antibody titres were assessed for a total of 76 serum samples from 39 (51%) Lupus patients and 37 (49%) healthy Controls. Healthy individuals showed the highest levels of nAB (1638.0 titre median), which were like not treated SLE subjects (1361.5 titre median). Treated patients presented substantially lower nAB titres compared to Healthy subjects: a 73% decrease for First-Line patients (p-value = 0.0135), 56% for patients received a Second-Line treatment (p-value = 0.2218) and 72% for Third-Line treated patients (p-value = 0.0104). A multivariate analysis pointed to Glucocorticoids as the most associated factor with declining nAB levels (75% decrease, p-value = 0.0037), and the one explaining, to a large extent, the lower acquired response in treated SLE patients. Furthermore, a significant reduction in nAB titres was observed for patients treated with Rituximab compared to Healthy subjects (89% decrease, p-value= 0.0008) (Figure 1). Conclusion: Medium-term response of SLE patients to SARS-CoV-2 vaccination, as measured by the titre of nABs, may be compromised by Glucocorticoids and Rituximab users. This reduced response likely translates into a higher probability of COVID-19 infection These fndings might help to inform recommendations in vaccination protocols for SLE patients.