ObjectivesTo better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs).MethodsPatients and controls from a large COVID-19 study, with (1) no previous history of COVID-19, (2) negative baseline anti-SARS-CoV-2 IgG test and (3) SARS-CoV-2 vaccination at least 10 days before serum collection were measured for anti-SARS-CoV-2 IgG. Demographic, disease-specific and vaccination-specific data were recorded.ResultsVaccination responses from 84 patients with IMID and 182 controls were analysed. While all controls developed anti-SARS-CoV-2 IgG, five patients with IMID failed to develop a response (p=0.003). Moreover, 99.5% of controls but only 90.5% of patients with IMID developed neutralising antibody activity (p=0.0008). Overall responses were delayed and reduced in patients (mean (SD): 6.47 (3.14)) compared with controls (9.36 (1.85); p<0.001). Estimated marginal means (95% CI) adjusted for age, sex and time from first vaccination to sampling were 8.48 (8.12–8.85) for controls and 6.90 (6.45–7.35) for IMIDs. Significantly reduced vaccination responses pertained to untreated, conventionally and anticytokine treated patients with IMID.ConclusionsImmune responses against the SARS-CoV-2 are delayed and reduced in patients with IMID. This effect is based on the disease itself rather than concomitant treatment.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystemic disease classified both amongst hypereosinophilic disorders and ANCA-associated vasculitis. Vessel inflammation and eosinophilic proliferation are the hallmarks of the disease and main effectors of organ damage. Two distinct disease phenotypes have classically been described according to ANCA-status: the ANCA-negative subset with eosinophil-driven manifestation and the ANCA-positive one with vasculitic manifestations. An analogous dichotomization has also been backed by histological findings and a distinct genetic background. EGPA is typically consider a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis. Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils. Thus, the pathogenesis of EGPA seems to be mediated by two coexisting mechanisms. However, the verbatim application of this strict dualism cannot always be translated into routine clinical practice. In the present review we describe the current knowledge on the eosinophilic and ANCA-mediated aspects of EGPA pathogenesis. Finally, we review the rationale of the currently proposed EGPA dichotomy and future research perspectives.

ObjectivesTo test whether patients with immune-mediated inflammatory disease (IMIDs), who did not respond to two doses of the SARS-CoV-2 vaccine, develop protective immunity, if a third vaccine dose is administered.MethodsPatients with IMID who failed to seroconvert after two doses of SARS-CoV-2 vaccine were subjected to a third vaccination with either mRNA or vector-based vaccines. Anti-SARS-CoV-2 IgG, neutralising activity and T cell responses were assessed at baseline and 3 weeks after revaccination and also evaluated seprarately in rituximab (RTX) and non-RTX exposed patients.Results66 non-responders were recruited, 33 treated with RTX, and 33 non-exposed to RTX. Overall, 49.2% patients seroconverted and 50.0% developed neutralising antibody activity. Seroconversion (78.8% vs 18.2%) and neutralising activity (80.0% vs 21.9%) was higher in non-RTX than RTX-treated patients with IMID, respectively. Humoral vaccination responses were not different among patients showing positive (59.3%) or negative (49.7%) T cell responses at baseline. Patients remaining on mRNA-based vaccines showed similar vaccination responses compared with those switching to vector-based vaccines.ConclusionsOverall, these data strongly argue in favor of a third vaccination in patients with IMID lacking response to standard vaccination irrespective of their B cell status.

At the beginning of the COVID-19 pandemic, patients with immune-mediated inflammatory diseases were considered to be at high risk for SARS-CoV-2 infection and the development of severe COVID-19. Data collected over the past year, however, suggest that a diagnosis of inflammatory arthritis, psoriasis, or inflammatory bowel diseases does not increase risk for SARS-CoV-2 infection or severe COVID-19 compared with people without these diseases. Furthermore, substantial data suggest that certain medications frequently used in patients with immune-mediated inflammatory diseases, in particular cytokine inhibitors, might even lower the risk for severe COVID-19. Conversely, glucocorticoids and potentially B-cell-depleting treatments seem to worsen COVID-19 outcomes. Additionally, the first data on SARS-CoV-2 vaccination in patients with these diseases suggest that tolerability of vaccination in patients with immune-mediated inflammatory diseases is good, although the immune response to vaccination can be somewhat reduced in this patient group, particularly those taking methotrexate or CD20-targeted treatment.

Objective B cell depletion is an established therapeutic principle in a wide range of autoimmune disease. However, B cells are also critical for inducing protective immunity after infection and vaccination. We therefore assessed humoral and cellular immune responses after infection with or vaccination against severe acute respiratory syndrome coronavirus ‐2 (SARS‐CoV‐2) in B cell depleted patients and B cell competent healthy controls. Methods Antibody (ELISA) and T cell (IFNγ ELISPOT) responses against the SARS‐CoV‐2 spike S1 and nucleocapsid proteins were assessed in a limited number of infected (N=6) and vaccinated (N=8) B cell depleted autoimmune patients as well as infected (N=30) and vaccinated (N=30) healthy controls. Results As expected, B and T cell responses to the nucleocapsid were observed only after infection, while respective responses to spike S1 were found both after infection and vaccination. A SARS‐CoV‐2 antibody response was observed in all vaccinated controls (30/30, 100%) but in none (0/8) of the vaccinated B‐cell‐depleted patients. In contrast, after SARS‐CoV‐2 infection, both B‐cell‐depleted patients (spike S: 5/6, 83%; nucleocapsid 3/6, 50%) and healthy controls (spike S: 28/30, 94%; nucleocapsid 28/30, 93%) developed antibodies. T cell responses against the spike S1 and nucleocapsid proteins were found in both infected and vaccinated B cell depleted subjects and in the controls. Conclusion These data show that B cell depletion completely blocks humoral but not T cell SARS‐CoV‐2 vaccination response. Furthermore, limited humoral immune responses are found in B cell depleted patients after SARS‐CoV‐2 infection.