ABSTRACT
Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders (IMIDs) treated with specific immunosuppressants and immunomodulating agents. The objective of this study is to investigate the humoral immune response after SARS-CoV-2 vaccination in patients using immunosuppressive and immunomodulating mono- and combination therapies, focussing on frequently prescribed therapies for inflammatory neuromuscular diseases. Methods: National prospective observational cohort study in selected patients with prevalent IMIDs including neuromuscular disease, and immunosuppressive or immunomodulating monotherapy (n=1273), combination therapies (n=419), patients without immunosuppressants (n=473), and healthy controls (n=174). Anti-RBD IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses, i.e. vaccination after previous SARS-CoV-2 infection, were studied as a proxy for recall responses. Findings: Sera from 1869 participants without and 470 participants with previous SARS-CoV-2 infection were analysed. We included 168 (7 2%) patients with inflammatory neuropathies and myopathies, and 127 (5 4%) patients with myasthenia gravis. Humoral responses did not differ between disorders. Anti-CD20 therapy and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks (RR) for reaching seroconversion following standard vaccination (RR: 0 32 and 0 61 respectively). The monotherapies corticosteroids, purine antagonists, methotrexate, mycophenolate mofetil and IVIg were not associated with a lower RR for reaching seroconversion (RR: 0 97, 0 98, 1 01, 0 86, and 0 99, respectively). Similarly, corticosteroids combined with either methotrexate or purine antagonists was not associated with a lower RR for reaching seroconversion (RR 0 89). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments but not for anti-CD20 therapies. Most immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that, in subgroups, did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment. Interpretation: Humoral responses following vaccination are impaired by specific immunosuppressants, most relevant for neuromuscular diseases being anti-CD20 and mycophenolate mofetil combination treatments. After standard vaccination regimens most immunosuppressants show equal seroconversion to controls although antibody titres may be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate in loss of (short term) protection. Alternatively, in immunosuppressants showing poor humoral responses after standard vaccination regimens such as, a third vaccination resulted in additional seroconversion in mycophenolate mofetil combination treatments whereas the effect for anti-CD20 therapy was limited.
ABSTRACT
Importance: Viral infection or vaccination has the potential to increase disease activity in immune-mediated neuromuscular diseases. Objective: We aimed to evaluate whether SARSCoV- 2 vaccination and infection leads to increase of disease activity in patients with immune-mediated neuromuscular diseases. Methods: This is an interim analysis of a subset of patients from an ongoing prospective multi-center cohort study on SARS-CoV-2 vaccination in patients with various immune mediated inflammatory diseases in the Netherlands, the Target to-B!-COVID study (T2B!). Patients received digital questionnaires every two months from study entry to assess disease activity compared to previous visit using a 5-point Likert scale. In addition, in case of SARS CoV-2 infection (prior to vaccination) patients received an extra questionnaire to assess disease activity in the four weeks after infection. In cases of self-reported increase of disease activity, medical files were used to assess whether disease activity was reported by the treating physician, and whether changes were made in type or dose of immunosuppressive or immunomodulating treatment. Results: In total, we included 303 patients with immune-mediated neuromuscular disease of which 127 patients with inflammatory neuropathies, 133 patients with myasthenia gravis, and 43 patients with myositis. In the four months after completed vaccination, 67 (22.1%) patients indicated an increase in disease activity, of which 62 (93%) was reported as worse and 5 (7%) as much worse. In 10 (3.3%) of the cases with self-reported increase, disease activity was also reported by the treating physician in the medical chart. In 4 (1.3%) of patients with self-reported increase disease activity treatment was adjusted because of the increase in disease activity. A SARS-CoV-2 infection prior to vaccination occurred in 24 (8%) patients, from which 3 (12.5%) indicated an increase in disease activity, not leading to change in treatment. Conclusion: Increase of disease activity after SARS-CoV-2 vaccination or infection was reported infrequently, and was self-limiting in most cases. Findings from our cohort may help physicians in neuromuscular disease to adequately inform patients on the risk of increased disease activity due to SARS-CoV-2 vaccination or infection. Full and verified results will be reported at the ICNMD 2022.
ABSTRACT
Background The aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). Methods The Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this , we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs. Results Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates. Conclusion No immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this as this might negatively impact the current submission process.
ABSTRACT
INTRODUCTION: Patients with Glycogen Storage Disease type II (GSDII), an inheritable metabolic myopathy also known as Pompe disease, are considered to be at risk for severe COVID-19 due to a reduced respiratory function and a tendency to be overweight. However, so far little is known about the course of SARS-CoV-2 infection and side effects of COVID-19 vaccinations in patients with GSDII. METHODS: 169 Dutch Pompe patients are followed at the Erasmus MC Rotterdam. During the COVID-19 pandemic patients were requested to directly inform their physicians about SARS-CoV-2 infection. Infected patients were interviewed regularly by telephone until their symptoms subsided. Furthermore, all patients eligible for vaccination on 16-7-2021 (≥ 17 years, n = 122) were asked to complete a questionnaire. RESULTS: To date, fifteen patients (8.9% of our cohort) reported a SARS-CoV-2 infection (classic infantile Pompe disease n = 5, late onset n = 10). No patients were admitted to hospital or needed intensivation of ventilatory support. All patients made a recovery within 19 days. 41.8% of patients filled in our questionnaire regarding vaccination, of whom 98% were vaccinated. Besides one case of perimyocarditis, only mild side effects were reported. CONCLUSION: Overall, patients with Pompe disease showed mild symptoms from infection with SARS-CoV-2. All patients made a full recovery. Side effects after vaccination were mostly mild.