ABSTRACT
BackgroundPatients suffering from systemic autoimmune rheumatic disease (SARD) display poor antibody development after two doses of mRNA vaccinations leaving these patients with only limited humoral protection against severe SARS-CoV-2 disease courses. Of key interest is the effect of conventional synthetic (csDMARD) and biological/ targeted drugs (b/tsDMARDs) disease modifying antirheumatic drugs on the time of protection.ObjectivesTo compare antibody titer development in patients with vasculitis and connective tissue disease (CTD) with healthy controls 6 months after two mRNA vaccinations and after third immunization. To analyze factors, that affect the velocity of titer decline, well as qualitative humoral response.MethodsPatients with SARD were enrolled and matched for gender and age with healthy control subjects (HC) and the humoral response after 6 months to two doses of mRNA vaccine BNT162b2 in terms of SARS-COV-2 antibody titer was assessed. In addition to binding antibody units (BAU) we also analyzed neutralizing antibodies. Patients receiving B-cell depleting therapy and those with prior SARS-CoV-2 infection (via detection of nucleocapsid antibodies) were excluded. Differences between two groups were calculated with Wilcoxon signed-rank test.ResultsA total of 53 patients with SARD (42 patients suffering from connective tissue disease and 11 with vasculitis respectively) and 73 HC were analysed. Interestingly only patients receiving a combination therapy of different csDMARDs/ b/tsDMARDs demonstrated diminished antibody titers 6 months after two doses of mRNA vaccine (p-value p-value<0,001), whereas patients receiving only csDMARD as monotherapy displayed comparable antibody levels to healthy controls. This effect was equalized after a third booster vaccination (p-value=0,13). Concerning disease entities, patients with vasculitis seemed to have lower BAU than HC (p-value<0,05) and patients suffering from CTD. After third vaccination both patient groups had lower antibody levels than HC (vasculitis: p-value <0,0001;CTD: p-value p-value<0,01). Lower antibody levels before third vaccination correlated with lower antibodies after third immunization.ConclusionPatients with autoimmune rheumatic diseases undergoing combination therapy may be more vulnerable to SARS-CoV-2 infection, due to reduced antibody levels 6 months following two doses of mRNA vaccine. Our data strongly recommends antibody measurements in patients receiving combination therapy and individualized earlier booster vaccination.Figure 1.Anti-SARS-Cov-2 S antibody titers. A: Antibody titers measured 6 months after two doses of mRNA vaccination in patients with connective tissue disease, vasculitis and healthy controls. B, Antibody levels according to disease entity. AB: antibody;BAU: binding antibody unit;CTD: connective tissue disease;HC: healthy control;mono: disease modifying anti-rheumatic drug monotherapy;combination: combination therapy of disease modifying anti-rheumatic drugs;RBD: receptor binding domain;[Figure omitted. See PDF]Table 1.Demographic parameters and therapy of study participants.SARD (n=53)HC (n=73)Age, mean (standard deviation)53.55 (±14.04)51.27 (±14.07)Female45 (84.9%)47 (64.4%)Connective tissue disease42 (79%)Vasculitis11 (21%)csDMARD or b/tsDMARD monotherapy22 (41%)csDMARD and/or b/tsDMARD combination therapy13 (25%)No therapy18 (34%)Methotrexate8 (15%)Mycophenolate mofetil10 (19%)Hydroxychloroquine17 (32%)Azathioprine8 (15%)Belimumab3 (6%)Tocilizumab3 (6%)Glucocorticoid dose 1. vaccination, mean (standard deviation)2.8 (±10.8)Glucocorticoid dose 2. vaccination, mean (standard deviation)2.6 (±10.7)SARD: Systemic autoimmune rheumatic disease, HC: Healthy controls, csDMARD: conventional synthetic disease modifying antirheumatic drugs and b/tsDMARD: biological/ targeted drugs disease modifying antirheumatic drugsREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsElisabeth Simader Speakers bureau: Lilly, Thomas Deimel: None declared, Felix Kartnig: None declared, Selma Tobudic: None declared, Helmuth Hasla her Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Thomas Maria Karonitsch: None declared, Daniel Mrak: None declared, Thomas Nothnagl: None declared, Thomas Perkmann: None declared, Helga Lechner-Radner: None declared, Judith Sautner: None declared, Florian Winkler: None declared, Heinz Burgmann Speakers bureau: speaker fees from Shionogi, Pfizer, MSD, Paid instructor for: advisory boards for Valneva, MSD, Gilead, Consultant of: consulting fees from MSD, Pfizer, Takeda, Gilead, Daniel Aletaha Speakers bureau: other from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: grants from Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Stefan Winkler: None declared, Stephan Blüml Speakers bureau: personal fees from Abbvie, personal fees from Novartis, Peter Mandl Speakers bureau: reports speaker fees from AbbVie, Janssen and Novartis, Grant/research support from: research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB.
ABSTRACT
BackgroundA 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed.ObjectivesIt remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.Methods50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.ResultsAt week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781 – 10208] versus 9650 BAU/ml [6633 - 16050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological diseases modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported.ConclusionDue to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsDaniel Mrak Consultant of: AstraZeneca, Felix Kartnig: None declared, Daniela Sieghart: None declared, Elisabeth Simader Speakers bureau: Lilly, Helga Radner Speakers bureau: Gilead, Merck Sharp and Pfizer, Peter Mandl: None declared, Lisa Göschl: None declared, Philipp Hofer: None declared, Thomas Deimel: None declared, Irina Gessl: None declared, Renate Kain Speakers bureau: Otsuka, Consultant of: AstraZeneca, Takeda Pharma, MEDahead and Janssen Cilag, Stefan Winkler: None declared, Josef S. Smolen Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Gilead-Galapagos, Janssen, Lilly, Pfizer, R-Pharma, Samsung, Sanofi, Chugai, Merck Sharp & Dohme, Novartis-Sandoz Roche, Samsung and UCB, Grant/research support from: Abbvie, AstraZeneca, Lilly, Novartis, and Roche, Thomas Perkmann: None declared, Helmuth Haslacher Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Consultant of: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Grant/research support from: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Leonhard Heinz: None declared, Michael Bonelli Consultant of: EliLilly.
ABSTRACT
Due to the COVID pandemic more and more people suffer from mid-to long-term problems associated with it. COVID can also cause a wide range of health issues over a longer period of time, which has been called Long COVID. Due to the wide range of symptoms and the fact that Long COVID is relatively new, there is a lack of applications supporting Long COVID patients. In this paper, a newly developed solution of a Long COVID patient support application is being discussed. It is based on the previous identification of requirements from questionnaires of patients with Long COVID, where they expressed their needs and wishes for such a solution with additional identified ones. This paper focuses on designing and developing an application containing the respective derived requirements to help and support people suffering from Long COVID. © 2022 IEEE.
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Background: Vaccination efficiency has been demonstrated to be reduced in patients with systemic autoimmune rheumatic disease (SARD) compared with the general population. Objectives: To assess the humoral response to mRNA vaccine in patients with (SARD) and the effect of immunosuppressive medication in a matched cohort study. Methods: Patients with SARD were enrolled and matched 1:1 for gender and age with healthy control subjects (HC). Differences in the humoral response to two doses of mRNA vaccine BNT162b2 in terms of seroconversion rate and SARS-COV-2 antibody titer between the two groups and impact of treatment within SARD patients was assessed using Fisher's exact test, Student's t-test, Mann-Whitney test and Kruskal-Wallis test, adjusting for multiple testing. Results: We enrolled 82 patients with SARD and 82 matched HC (Table 1). Among patients the seroconversion rate was signifcantly lower after the 1st dose (65% compared to 100% in HC, p<0.0001) but levelled up after the 2nd dose (94% vs. 100%). While the difference in seroconversion rate was independent of treatment regime (no disease modifying anti-rheumatic drug (DMARD), DMARD monother-apy, DMARD combination therapy), the seroconversion rate of SARD patients on mono-or combination DMARD therapy was also signifcantly lower as compared to those receiving no DMARD therapy (56% for monotherapy and 57% for combination therapy compared to 77% for no DMARD therapy, p=0.002 and p=0.004 respectively;Figure 1A). Seroconversion rate after the 2nd dose was signifcantly lower for patients on combination DMARD therapy compared to all other groups (81% compared to 95% for monotherapy, and 100% for both no DMARD therapy and HC respectively, all p<0.0001);also antibody titers after the 2nd dose were lower when comparing patients on combination DMARD therapy to all other groups (49 binding antibody units (BAU)/ml versus 1673 BAU/ml in HC, p<0.0001;2500 BAU/ml in those on no DMARD therapy, p<0.0001;and 687 BAU/ml in those on DMARD monotherapy, p=0.0072;Figure 1B). Considering effects of individual compounds, mycophenolate mofetil in mono-or combination therapy led to lower antibody titers after the 2nd dose as compared to HC or patients receiving no DMARDs (2 BAU/ml versus 1673 BAU/ml and 2500 BAU/ml respectively, both p<0.0001). Conclusion: Patients with SARD showed a good response after the 2nd vaccination with the mRNA vaccine. However, the choice of immunosuppressive regimen has a marked effect on both seroconversion rate and overall antibody titer.
ABSTRACT
Background: Little is known about the duration of humoral antibody levels after two SARS-CoV-2 mRNA vaccinations in patients with immunosuppression. During this ongoing global epidemic, it is of essential interest to gather information about the time of protection after initial immunization in the vulnerable patients receiving either conventional synthetic disease modifying antirheumatic drugs (csDMARD) or biological/targeted drugs (b/tsDMARDs). Objectives: In this study we compared the antibody level development after vaccination and after six months in patients with infammatory arthritis, infammatory bowel disease (IBD) and healthy controls. Furthermore, we assessed factors affecting the quality and quantity of the humoral response. Methods: We enrolled 85 healthy controls (HC), 75 patients with rheumatoid arthritis and spondyloarthritis and 41 patients suffering from IBD. Patients treated with B-cell depleting therapies were excluded from this study. Binding antibody units were measured after vaccination and 6 or more months. Neutralizing antibodies were measured after 6 months. Multivariate regression analyses analyzing factors associated with low titers after 6 months was performed. Results: We found that patients with infammatory arthritis or IBD showed reduced anti-SARS-CoV-2 S titers compared to HC. When we stratifed for therapies, we found that patients receiving conventional synthetic disease modifying antirheumatic dugs (csDMARDs) had comparable anti-SARS-CoV-2 S titers to HC. In contrast, patients receiving biological or targeted synthetic (b/tsDMARDs) showed reduced anti-SARS-CoV-2 Igs as well as neutralizing antibody titers compared with healthy controls (HC) or patients receiving conventional synthetic (cs)DMARDs. We further show that anti-SARS-CoV-2 titers declined more rapidly in patients receiving b/tsDMARDs compared to HC, leading to a 50 percent reduction in vaccination-associated protection time in patients receiving b/tsD-MARDs when compared to those receiving csDMARDs or even HC. In multi-variate regression analyses, we found that in addition to the type of treatment, also age as well as corticosteroid use were associated with reduced anti-SARS-CoV-2 S titers. Conclusion: Patients under ongoing b/tsDMARDs therapy exposed an accelerated waning of anti-SARS-CoV-2 S titers and therefore decreased immunity and protection against severe Covid-19 infections over time. These results may lead to more personalized approaches for further vaccination strategies in this group of immunosuppressed patients.
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Background: Due to the SARS-CoV-2 pandemic, the mentoring programs of the competence centers for specialist training in family medicine nationwide were converted to digital formats. Acceptance of online implementation was evaluated on an ongoing basis. Methods: The study included the evaluations of the physicians in specia-list training participating in the mentoring program in Saxony, Hessen and Berlin from April to July 2020. In total, feedback from 135 mentees from 36 online mentoring sessions could be evaluated descriptively and content-analytically. The online mentoring meetings were evaluated by means of closed and open questions. Results: The online mentoring session were mainly evaluated positively. The participants are grateful for the opportunities for exchange even at times of limited contact. At the time of the survey, many physicians would like to have face-to-face meetings as soon as this is possible again. Conclusions: Networking and focused exchange in the context of mentoring sessions are possible online. In the course of the pandemic, the technical and didactic quality of the offers has improved. Follow-up studies should determine the extent to which online mentoring offers are a good addition to existing mentoring offers that is accepted by the target group and enables other mentees to participate. © Deutscher rzteverlag ;ZFA ;Zeitschrift fr Allgemeinmedizin.
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We report the case of a female, 77 year old patient with multi-localized skin infarctions following vaccination with mRNA-1273 (Moderna). This phenomenon is to our knowledge otherwise only seen in infection-associated purpura fulminans - which was thoroughly ruled out in our patient. This report demonstrates that we need to be vigilant of a wider array of vascular phenomena related to Covid vaccinations.
Subject(s)
COVID-19 , Purpura Fulminans , 2019-nCoV Vaccine mRNA-1273 , Aged , COVID-19 Vaccines , Female , Humans , Purpura Fulminans/etiology , SARS-CoV-2 , Vaccination/adverse effectsABSTRACT
In emergency situations, the people most affected are often those who are already vulnerable, and this certainly includes children. The "new normal" we are living in to defend ourselves against this tiny yet dangerous enemy has serious repercussions on children's lives. This becomes even more evident if we think of those children who are doubly vulnerable - they are even more fragile because they live in conditions of particular hardship when they live outside their family, have a disability, or live in poverty. Since the beginning of the Covid-19 pandemic, we have witnessed the proliferation of numerous initiatives by various national and international children's rights institutions, which have called for urgent measures to protect children's rights. At this precise moment, the concept of the child's best interests is also reinterpreted as a result of a reasonable compression of certain children's rights and the prevalence of others. The present paper will attempt an analytical reconstruction of children's fundamental rights by analyzing how these rights have changed during the pandemic. In fact, it is necessary to know if and/or how much have the rights of minors changed as a result of the emergency. The second part of the paper is dedicated to the question of which children's rights will be most compromised or changed in the post-Covid-19 era. In reflecting on the inevitable consequences that the pandemic will leave on the delicate balance of the development of children's rights, the author will offer some proposals on how to contain the encountered difficulties.
ABSTRACT
As a result of the SARS-CoV-2 pandemic, all competence centers for specialist training in family medicine faced similar challenges of converting their mentoring programs to digital formats. Existing communication structures based on the national integration of the responsible organizers for the mentoring program, helped to make it possible for resources to be pooled and available resources to be exploited. The working group‘s way of operation might serve as an example for other working groups. © Deutscher Ärzteverlag.
ABSTRACT
Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure (p = 0.003), positively tested family members (p = 0.04), and travel history (p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose (p = 0.002) and altered taste or smell (p < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.