Objectives Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation. Methods Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls. Results All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p Conclusions The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.

https://ard.bmj.com/content/annrheumdis/80/10/1345.full.pdf

SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity.

Treatment with rituximab (RTX), a monoclonal antibody targeting CD20, constitutes an important therapeutic strategy for patients with inflammatory rheumatic diseases. Some recent reports have already highlighted the risk of SARS-CoV-2 infection in patients treated with RTX.1–4 Besides the risk of a more severe disease course during B cell depleting therapy, a major concern relates to a risk of reduced immunogenicity of vaccination. Therefore, the question arises if patients should withhold or interrupt RTX therapy around COVID-19 vaccination or delay vaccination. To address this question, we have assessed antibody response and T cell mediated immune response to the BNT162b2 (Pfizer/BioNTech) vaccine in patients undergoing RTX treatment at the end of the treatment interval.

Five patients under regular and recent RTX treatment were selected for COVID-19 vaccination with BNT162b2 (Pfizer/BioNTech). A detailed description of the methods and the patient characteristics (online supplemental table S1) can be found in the online supplemental material. The last RTX infusion was administered between 4 and 12 months ago (online supplemental figure S1). At the time of the vaccination, peripheral CD19+ B cells could only be detected in two patients (online supplemental table S2). Antibodies against the SARS-CoV-2 nucleocapsid …

https://ard.bmj.com/content/annrheumdis/80/10/1355.full.pdf

SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response.

COVID-19 infection among autoimmune rheumatic disease patients: Data from an observational study and literature review.

We read with great interest the article by Geisen et al .1 The authors reported a considerable immunogenicity of mRNA vaccines against SARS-CoV-2 in patients with chronic inflammatory diseases receiving immunosuppression; noteworthy, none was on B-cell depleting agents.

Rituximab (RTX) is one of the mainstays of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) treatment, both for induction and maintenance therapy2; of note, recent data have shown that RTX therapy was associated with poorer COVID-19-related outcomes in patients with rheumatic diseases.3 

In the absence of an effective treatment, vaccination would be a promising tool to prevent severe COVID-19 in immunocompromised patients.

Only four cases addressing the issue of antibody production after SARS-CoV-2 infection in patients with AAV treated with RTX are available in literature,4–6 while no data about antibody production after vaccination have been published yet.

We describe here the case of two AAV patients who did not produce neutralising antibodies after mRNA vaccination against SARS-CoV-2 (cases 1 and 2); we also report the case of a patient who experienced COVID-19 while B-cell depleted without seroconversion (case 3).

Case 1: …

https://ard.bmj.com/content/annrheumdis/80/10/e158.full.pdf

Correspondence on 'Immunogenicity and safety of anti-SARS-Cov-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort'

The outcomes of COVID-19 in patients treated with biologic agents are a subject of intense investigation. Recent data indicated that patients under rituximab (RTX) may carry an increased risk of serious disease. We performed an electronic search in Medline and Scopus using the keywords rituximab and COVID-19. We present a rare case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following RTX treatment. In a relevant literature search, we identified 18 cases of patients with rheumatic diseases (6 RA, 8 ANCA vasculitis, 3 systemic sclerosis and 1 polymyositis) treated with RTX who experienced an atypical and/or prolonged course of COVID-19 pneumonia with no evidence of cytokine storm. Our case indicates that RTX may unfavorably affect outcomes following SARS-CoV-2 infection. B cell depletion may dampen the humoral response against the virus; we may hypothesize that B cell-depleted patients may be protected from cytokine storm but on the other hand may have difficulties in virus clearance leading to a protracted course. Taking into account that COVID-19 vaccines are available we may consider delaying RTX infusions at least in patients without life threatening disease, until vaccination is completed.

/pdf/protracted-severe-covid-19-pneumonia-following-rituximab-j3av1z197m.pdf

Protracted severe COVID-19 pneumonia following rituximab treatment: caution needed.

/pdf/timing-of-rituximab-and-immunoglobulin-level-influence-the-1ynq1lmmfi.pdf

Timing of Rituximab and immunoglobulin level influence the risk of death for COVID-19 in ANCA-associated vasculitis.

Lung involvement in systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS) has extensively been outlined with a multiplicity of different manifestations. In SLE, the most frequent finding is pleural effusion, while in pSS, airway disease and parenchymal disorders prevail. In both cases, there is an increased risk of pre-capillary and post-capillary pulmonary arterial hypertension (PAH) and pulmonary venous thromboembolism (VTE). The risk of VTE is in part due to an increased thrombophilic status secondary to systemic inflammation or to the well-established association with antiphospholipid antibody syndrome (APS). The lung can also be the site of an organ-specific complication due to the aberrant pathologic immune-hyperactivation as occurs in the development of lymphoma or amyloidosis in pSS. Respiratory infections are a major issue to be addressed when approaching the differential diagnosis, and their exclusion is required to safely start an immunosuppressive therapy. Treatment strategy is mainly based on glucocorticoids (GCs) and immunosuppressants, with a variable response according to the primary pathologic process. Anticoagulation is recommended in case of VTE and multi-targeted treatment regimens including different drugs are the mainstay for PAH management. Antibiotics and respiratory physiotherapy can be considered relevant complement therapeutic measures. In this article, we reviewed lung manifestations in SLE and pSS with the aim to provide a comprehensive overview of their diagnosis and management to physicians taking care of patients with connective tissue diseases.

https://journals.sagepub.com/doi/pdf/10.1177/1759720X211040696

Giulia Del Frate

Papers

Timing of Rituximab and immunoglobulin level influence the risk of death for COVID-19 in ANCA-associated vasculitis.

Diagnosis and management of lung involvement in systemic lupus erythematosus and Sjögren’s syndrome: a literature review: