Intensity and longevity of SARS-CoV-2 vaccination response in patients with immune-mediated inflammatory disease: a prospective cohort study.

Background: Concerns have been raised about the reduced immunogenicity of vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory diseases and the higher risk of breakthrough infections. The objective of our study was to investigate the intensity and longevity of SARS-CoV-2 vaccination responses in patients with immune-mediated inflammatory diseases, and to assess the effects of diagnosis, treatment, and adapted vaccination schedules. Methods: SARS-CoV-2 IgG antibody response after SARS-CoV-2 vaccination was measured over time in a large prospective cohort of healthy controls and participants with immune-mediated inflammatory diseases (attending or admitted to affiliated centres) between Dec 15, 2020, and Dec 1, 2021. Cohort participants with immune-mediated inflammatory diseases and control participants with no diagnosis of immune-mediated inflammatory diseases, were eligible for this analysis. Demographic data and disease-specific data were collected using a questionnaire. Humoral response was compared across treatment and disease groups, and with respect to the receipt of additional vaccinations. SARS-CoV-2 antibody response was measured by ELISA using optical density ratio units and modelled over time with age and sex adjustment using mixed-effects models. Using these models, marginal mean antibody titres and marginal risks of a poor response (optical density ratio <1·1) were calculated for each week starting from week 8 after the first vaccination to week 40. Findings: Among 5076 individuals registered, 2535 participants with immune-mediated inflammatory diseases (mean age 55·0 [15·2] years; 1494 [58·9%] women and 1041 [41·1%] men) and 1198 healthy controls (mean age 40·7 [13·5] years; 554 [46·2%] women and 644 [53·8%] men) were included in this analysis. Mean antibody titres were higher in healthy controls compared with people with immune-mediated inflammatory diseases at all timepoints, with a peak antibody response in healthy controls (mean optical density ratio 12·48; 95% CI 11·50-13·53) of more than twice that in participants with immune-mediated inflammatory diseases (5·50; 5·23-5·77; mean difference 6·98; 5·92-8·04). A poor response to vaccination was observed in participants with immune-mediated inflammatory diseases who were taking B-cell inhibitors (peak mean difference from healthy controls 11·68; 10·07-13·29) and T-cell inhibitors (peakmean difference from healthy controls 10·43; 8·33-12·53). Mean differences in antibody responses between different immune-mediated inflammatory diseases were small. Participants with immune-mediated inflammatory diseases who were given a third vaccine dose had higher mean antibody titres than did healthy controls vaccinated with two vaccine doses at 40 weeks after the initial vaccination (mean difference 1·34; 0·01-2·69). Interpretation: People with immune-mediated inflammatory diseases show a lower and less durable SARS-CoV-2 vaccination response and are at risk of losing humoral immune protection. Adjusted vaccination schedules with earlier booster doses or more frequent re-doses, or both, could better protect people with immune-mediated inflammatory diseases. Funding: Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Research Council, Innovative Medicine Initiative, Friedrich-Alexander-Universität Erlangen-Nürnberg, Else Kröner-Memorial Foundation.

Impact of Cytokine Inhibitor Therapy on the Prevalence, Seroconversion Rate, and Longevity of the Humoral Immune Response Against SARS-CoV-2 in an Unvaccinated Cohort.

OBJECTIVE: To investigate the impact of biologic disease-modifying antirheumatic drug (bDMARD) treatment on the prevalence, seroconversion rate, and longevity of the humoral immune response against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). METHODS: Anti-SARS-CoV-2 IgG antibodies were measured in a prospective cohort of health care professional controls and non-health care controls and IMID patients receiving no treatment or receiving treatment with conventional or biologic DMARDs during the first and second COVID-19 waves. Regression models adjusting for age, sex, sampling time, and exposure risk behavior were used to calculate relative risks (RRs) of seropositivity. Seroconversion rates were assessed in participants with polymerase chain reaction (PCR)-positive SARS-CoV-2 infection. Antibody response longevity was evaluated by reassessing participants who tested positive during the first wave. RESULTS: In this study, 4,508 participants (2,869 IMID patients and 1,639 controls) were analyzed. The unadjusted RR (0.44 [95% confidence interval (95% CI) 0.31-0.62]) and adjusted RR (0.50 [95% CI 0.34-0.73]) for SARS-CoV-2 IgG antibodies were significantly lower in IMID patients treated with bDMARDs compared to non-health care controls (P < 0.001), primarily driven by treatment with tumor necrosis factor inhibitors, interleukin-17 (IL-17) inhibitors, and IL-23 inhibitors. Adjusted RRs for untreated IMID patients (1.12 [95% CI 0.75-1.67]) and IMID patients receiving conventional synthetic DMARDs (0.70 [95% CI 0.45-1.08]) were not significantly different from non-health care controls. Lack of seroconversion in PCR-positive participants was more common among bDMARD-treated patients (38.7%) than in non-health care controls (16%). Overall, 44% of positive participants lost SARS-CoV-2 antibodies by follow-up, with higher rates in IMID patients treated with bDMARDs (RR 2.86 [95% CI 1.43-5.74]). CONCLUSION: IMID patients treated with bDMARDs have a lower prevalence of SARS-CoV-2 antibodies, seroconvert less frequently after SARS-CoV-2 infection, and may exhibit a reduced longevity of their humoral immune response.

Humoral and Cellular Immune Responses to SARS-CoV-2 Infection and Vaccination in Autoimmune Disease Patients With B Cell Depletion.

OBJECTIVE: B cell depletion is an established therapeutic principle in a wide range of autoimmune diseases. However, B cells are also critical for inducing protective immunity after infection and vaccination. We undertook this study to assess humoral and cellular immune responses after infection with or vaccination against SARS-CoV-2 in patients with B cell depletion and controls who are B cell-competent. METHODS: Antibody responses (tested using enzyme-linked immunosorbent assay) and T cell responses (tested using interferon-γ enzyme-linked immunospot assay) against the SARS-CoV-2 spike S1 and nucleocapsid proteins were assessed in a limited number of previously infected (n = 6) and vaccinated (n = 8) autoimmune disease patients with B cell depletion, as well as previously infected (n = 30) and vaccinated (n = 30) healthy controls. RESULTS: As expected, B cell and T cell responses to the nucleocapsid protein were observed only after infection, while respective responses to SARS-CoV-2 spike S1 were found after both infection and vaccination. A SARS-CoV-2 antibody response was observed in all vaccinated controls (30 of 30 [100%]) but in none of the vaccinated patients with B cell depletion (0 of 8). In contrast, after SARS-CoV-2 infection, both the patients with B cell depletion (spike S1, 5 of 6 [83%]; nucleocapsid, 3 of 6 [50%]) and healthy controls (spike S1, 28 of 30 [93%]; nucleocapsid, 28 of 30 [93%]) developed antibodies. T cell responses against the spike S1 and nucleocapsid proteins were found in both infected and vaccinated patients with B cell depletion 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 after SARS-CoV-2 infection in patients with B cell depletion.

Prevalence of Depressive Symptoms in Patients With Psoriatic Arthritis: Have Numbers Changed During the COVID-19 Pandemic?

This longitudinal analysis compares the prevalence of depressive symptoms in patients with psoriatic arthritis in the context of the COVID-19 pandemic. Data from a national patient register in Germany were analyzed regarding the Patient Health Questionnaire 2 (PHQ-2) to identify cases suspicious for depression at two time points, i.e., before and during the COVID-19 pandemic. Only patients with complete concurrent information on the Disease Activity in Psoriatic Arthritis Score (DAPSA) were included in the analysis. The frequency of depressive symptoms in psoriatic arthritis patients during the COVID-19 pandemic did not differ from the prevalence rates measured before. In addition, prevalence rates for depressive symptoms did not differ when stratifying the patient sample for DAPSA levels of disease activity measured before the pandemic. These results were confirmed further in a sensitivity analysis, limiting the second PHQ-2 assessment to lockdown periods only. However, longitudinal data on the prevalence of depressive symptoms in patients with rheumatic diseases, in general, and psoriatic arthritis, in particular, are scarce in the context of the COVID-19 pandemic. For a sensible comparison of prevalence rates for depressive symptoms in the future, underlying SARS-CoV-2 infection rates and resulting local healthcare disruptions need to be taken into account, besides the potential use of different depression screening tools to evaluate resulting numbers sensibly and draw corresponding conclusions for patient care.

[Corona pandemic in the practice : A flashback and reflection from the rheumatological practice]. / Corona-Pandemie in der Praxis : Eine Rückblende und Reflexion aus der rheumatologischen Praxis.

The corona pandemic changed the lives of people in Germany in 2020. Completely new challenges had to be met in outpatient care and of course also in rheumatology practices. The rapid development, the constant changes, the readjustment, the accompaniment of patients and staff team in this global catastrophe are described. The influence on the daily work and the implementation of new scientific knowledge, e.g. the recommendations of the German Society of Rheumatology (DGRh), are reported. Experiences and insights into what can be learned and taken away from crisis situations are outlined. A detailed chronology of the events, taking the special rheumatological features into account, completes this report of experiences.

SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases.

OBJECTIVES: To better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). METHODS: Patients 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. RESULTS: Vaccination 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. CONCLUSIONS: Immune 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.

Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion.

Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection.