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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 ; 74(5): 783-790, 2022 05.
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.


Subject(s)
Antirheumatic Agents , Biological Products , COVID-19 , Antibodies, Viral , Antirheumatic Agents/therapeutic use , Cytokines , Humans , Immunity, Humoral , Immunoglobulin G , Prevalence , Prospective Studies , SARS-CoV-2 , Seroconversion
4.
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
5.
J Immunother Cancer ; 9(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1038424

ABSTRACT

BACKGROUND: Patients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer. METHODS: We analyzed data from 110 patients with laboratory-confirmed SARS-CoV-2 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe and Australia. The primary objective was to describe the clinical course and to identify factors associated with hospital and intensive care (ICU) admission and mortality. FINDINGS: Thirty-five (32%) patients were admitted to hospital and 18 (16%) died. All patients who died had advanced cancer, and only four were admitted to ICU. COVID-19 was the primary cause of death in 8 (7%) patients. Factors independently associated with an increased risk for hospital admission were ECOG ≥2 (OR 39.25, 95% CI 4.17 to 369.2, p=0.0013), treatment with combination ICI (OR 5.68, 95% CI 1.58 to 20.36, p=0.0273) and presence of COVID-19 symptoms (OR 5.30, 95% CI 1.57 to 17.89, p=0.0073). Seventy-six (73%) patients interrupted ICI due to SARS-CoV-2 infection, 43 (57%) of whom had resumed at data cut-off. INTERPRETATION: COVID-19-related mortality in the ICI-treated population does not appear to be higher than previously published mortality rates for patients with cancer. Inpatient mortality of patients with cancer treated with ICI was high in comparison with previously reported rates for hospitalized patients with cancer and was due to COVID-19 in almost half of the cases. We identified factors associated with adverse outcomes in ICI-treated patients with COVID-19.


Subject(s)
COVID-19/epidemiology , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19/virology , Cohort Studies , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Middle Aged , Neoplasms/immunology , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
6.
J Med Internet Res ; 22(12): e20064, 2020 12 29.
Article in English | MEDLINE | ID: covidwho-1007075

ABSTRACT

Following the rapid spread of a new type of coronavirus (SARS-CoV-2), nearly all countries have introduced temporary restrictions affecting daily life, with "social distancing" as a key intervention for slowing the spread of the virus. Despite the pandemic, the development or actualization of medical guidelines, especially in the rapidly changing field of oncology, needs to be continued to provide up-to-date evidence- and consensus-based recommendations for shared decision making and maintaining the treatment quality for patients. In this viewpoint, we describe the potential strengths and limitations of online conferences for medical guideline development. This viewpoint will assist guideline developers in evaluating whether online conferences are an appropriate tool for their guideline conference and audience.


Subject(s)
COVID-19 , Consensus , Humans , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
9.
J Dtsch Dermatol Ges ; 18(8): 795-807, 2020 08.
Article in English | MEDLINE | ID: covidwho-697169

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has far-reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS-CoV-2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS-CoV-2/COVID-19 with mediators of the acute phase of inflammation (TNF, IL-1, IL-6), type 1 and type 17 immune responses (IL-12, IL-23, IL-17, IL-36), type 2 immune reactions (IL-4, IL-13, IL-5, IL-31, IgE), B-cell immunity, checkpoint regulators (PD-1, PD-L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non-specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte-mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS-CoV-2/COVID-19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID-19 pandemic; some even appear to alleviate COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/prevention & control , Cytokines/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , COVID-19/therapy , Cytokine Release Syndrome/immunology , Humans , Immunotherapy , Th1 Cells/drug effects , Th1 Cells/immunology , Th17 Cells/drug effects , Th17 Cells/immunology
10.
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
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