Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines

Abstract

Objective The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. Methods Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. Results A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). Conclusion In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

The Third Dose Is the Charm: Effective Cellular and Humoral Immune Responses to Third COVID-19 Vaccine Doses in Immunosuppressed Nonresponders

“…9 ABA decreases T cell activation and priming by blocking CD28-CD80/CD86, which also decreases B cell activation due to the lack of T cell help. In this study, 8 ABA use was associated with decreased T and B cell responses. On the other hand, RTX targets B cells without a direct effect on T cells.…”

“…Current ACR guidelines recommend holding ABA, belimumab, cyclophosphamide, and other conventional or targeted synthetic immunomodulatory or immunosuppressive medications for 1 to 2 weeks and RTX for several months prior to each injection with the SARS-CoV-2 vaccine, when possible. 9 Data from Isnari and colleagues 8 support the CDC recommendation that the primary SARS-CoV-2 vaccination series should include 3 rather than 2 doses in immunocompromised patients. Further studies on the effect of immune suppression on host-pathogen responses are needed to develop more efficacious vaccines, vaccination strategies, and vaccine response monitoring for our immunosuppressed patient population.…”

“…[4][5][6][7] In this issue of The Journal of Rheumatology, Isnardi and colleagues evaluate the cellular and humoral responses after a third SARS-CoV-2 vaccine dose in patients with rheumatoid arthritis (RA) who did not develop detectable anti-SARS-CoV-2 antibodies following completion of the primary SARS-CoV-2 vaccine series. 8 Isnardi et al 8 enrolled 21 patients who met 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology criteria for RA from 2 sites in Argentina and who did not develop any detectable levels of SARS-CoV-2 antibodies after 2 doses of the SARS-CoV-2 vaccine. Blood was collected 21 to 40 days after the third vaccine dose to measure anti-SARS-CoV-2 antibodies with neutralizing activity, and T cell activity was quantified using an interferon-γ ELISA-based assay with the SARS-CoV-2 receptor binding domain from the spike protein.…”

“…Isnardi and colleagues 8 showed that a third dose of the SARS-CoV-2 mRNA vaccine can stimulate a robust immune response in previous primary series vaccine nonresponders. It is unknown whether any immunosuppressive medications were held prior to receiving any of the vaccine doses as currently recommended.…”

Efficacy and safety of inactivated SARS‐CoV‐2 vaccination in COVID‐19‐associated pneumonia among patients with rheumatic and musculoskeletal diseases: A real‐world retrospective observational study

“…RMD patients produce low levels of neutralizing antibodies due to impaired immune systems. But with multiple vaccine injections, they can still protect most patients from severe COVID‐19 41 . Thus, current guidelines recommend that patients with autoimmune and inflammatory rheumatism be vaccinated regardless of whether they use immunomodulators 28 …”