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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333072

ABSTRACT

Objectives: To investigate the intensity and longevity of SARS-CoV-2 vaccination response in patients with immune-mediated inflammatory disease (IMID) by diagnosis, treatment and adapted vaccination schedules. Methods SARS-CoV-2 IgG antibody response after SARS-CoV-2 vaccination was measured longitudinally in a large prospective cohort of healthy controls (HC) and IMID patients between December 2020 and 2021. Demographic and disease-specific data were recorded. Humoral response was compared across treatment and disease groups, and with respect to receipt of booster vaccinations. Age and sex adjusted SARS-CoV-2 antibody response was modelled over time. Marginal mean antibody levels and marginal risks of poor response were calculated at weekly intervals starting from week-8 after the first vaccination up to week 40. Results Among 5076 individuals registered, 2535 IMID patients and 1198 HC were eligible for this analysis. Mean antibody levels were higher in HC compared to IMIDs at all-time points, with peak antibody response in HC more than twice that in IMIDs (12.48 (11.52-13.52) vs. 5.71 (5.46-5.97)). Poor response to vaccination was observed in IMID patients treated with agents affecting B- and T-cell functions. Mean differences in antibody response between IMID diseases were small. After additional vaccinations, IMID patients could achieve higher antibody levels than HC vaccinated according to the two-dose schedule, even-though initial antibody levels were lower. Conclusions IMID patients show a lower and less durable SARS-CoV-2 vaccination response and are at risk to lose humoral immune protection. Adjusted vaccination schedules with earlier boosters and/or more frequent re-doses could better protect IMID patients.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321594

ABSTRACT

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 observed a significantly reduced incidence of SARS-CoV-2 infection 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.Authors David Simon and Koray Tascilar contributed equally to this work. Authors Markus F. Neurath and Georg Schett share senior authorship.

3.
Arthritis Rheumatol ; 2021 Dec 23.
Article in English | MEDLINE | ID: covidwho-1589173

ABSTRACT

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.

4.
Gastroenterology ; 160(3): 925-928.e4, 2021 02.
Article in English | MEDLINE | ID: covidwho-1575253
5.
Ann Rheum Dis ; 80(10): 1339-1344, 2021 10.
Article in English | MEDLINE | ID: covidwho-1243691

ABSTRACT

OBJECTIVE: To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. METHODS: Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. RESULTS: Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. CONCLUSIONS: In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

6.
Ann Rheum Dis ; 80(10): 1312-1316, 2021 10.
Article in English | MEDLINE | ID: covidwho-1220000

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , Rheumatic Diseases/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antirheumatic Agents/therapeutic use , Female , Humans , Male , Middle Aged , Rheumatic Diseases/drug therapy , SARS-CoV-2
7.
J Crohns Colitis ; 15(5): 864-868, 2021 May 04.
Article in English | MEDLINE | ID: covidwho-1216644

ABSTRACT

BACKGROUND AND AIMS: A similar course of COVID-19 in patients with inflammatory bowel diseases [IBD] and in the general population has been reported. However, disease prevalence in IBD patients is presently unknown. In this prospective observational study, we aimed at determining SARS-CoV2 infection prevalence in IBD patients treated with biologic therapy. METHODS: From IBD patients under biologic therapy and recruited from three different locations in Italy and Germany, 354 sera were evaluated for antibody presence by RBD ELISA. Control groups were: i] age-matched healthy subjects tested in the same time period in Milan, Italy; ii] healthy subjects collected in the pre-COVID era; iii] IBD patients under biologic therapy collected in the pre-COVID era. RESULTS: Eight out of 354 patients tested positive for the anti-RBD-SARS-CoV2 IgG antibody [prevalence 2.3%]. The percentage of IgG-positive patients among those recruited from Milan was significantly higher than among those recruited from other locations [prevalence 5.4% vs 0.4%, p <0.005]. IgG-positive patients reported a significantly higher incidence of fever, anosmia, and ageusia, and were more likely to have entered into close contact with COVID-19-positive subjects before the study enrolment. CONCLUSIONS: Seroprevalence of SARS-CoV2 in IBD patients treated with biologic therapy reflects values measured in the local general population. Specific symptoms and contact history with SARS-CoV2-infected individuals strongly increase the likelihood of SARS-CoV2 seropositivity.


Subject(s)
Antibodies, Viral/blood , Biological Therapy , COVID-19/epidemiology , Inflammatory Bowel Diseases/drug therapy , SARS-CoV-2/immunology , Adult , Ageusia/virology , Anosmia/virology , Case-Control Studies , Female , Fever/virology , Germany/epidemiology , Humans , Immunoglobulin G/blood , Inflammatory Bowel Diseases/epidemiology , Italy/epidemiology , Male , Middle Aged , Prevalence , Prospective Studies , Seroepidemiologic Studies
8.
Gastroenterology ; 160(3): 925-928.e4, 2021 02.
Article in English | MEDLINE | ID: covidwho-977281
9.
Nat Commun ; 11(1): 3774, 2020 07 24.
Article in English | MEDLINE | ID: covidwho-672188

ABSTRACT

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.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Cytokines/antagonists & inhibitors , Immune System Diseases/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Seroconversion , Adult , Antibodies, Viral/blood , COVID-19 , Female , Humans , Immunoglobulin G/blood , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Pandemics , Prevalence , Risk
10.
Visc Med ; 36(4): 338-342, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-618476

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, represents a potentially major challenge to patients with immune-mediated inflammatory diseases who are treated with immunomodulatory therapies. We report the case of an 18-year-old ulcerative colitis patient in sustained clinical remission who 4 days after application of her ongoing therapy with the anti-TNF antibody infliximab developed mild respiratory and abdominal symptoms. The patient was subsequently diagnosed with COVID-19 but did not need hospitalization. The clinical symptoms completely resolved within 1 week after onset and there was no change in ulcerative colitis activity. The recently applied anti-TNF therapy did not lead to exacerbation of the infectious symptoms. Current recommendations strongly favor continuation of effective maintenance anti-TNF therapy in inflammatory bowel disease patients, as there is no evidence for aggravated CO-VID-19 upon infection. It is unclear whether anti-TNF treatment might even have assisted in preventing worsening of COVID-19 and improving outcome. Further data in the group of immune-mediated inflammatory disease patients under anti-TNF therapy are urgently needed.

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