Association between physical activity and immunogenicity of an inactivated virus vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases

Abstract Immunocompromised individuals show lower vaccine immunogenicity, which may be modulated by physical activity. This prospective cohort study within a phase-4 vaccination trial investigated whether physical activity is associated with enhanced immunogenicity of Coronavac (SARS-CoV-2 inactivated vaccine) in patients with autoimmune rheumatic diseases (ARD) (n=898) and non-ARD (n=197) individuals without pre-existing immunogenicity to SARS-CoV-2 after receiving a two-dose vaccine schedule. Seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity were assessed. After controlling for covariates, active patients (≥150 min/week) exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary (≥150 min/week/<8h/day) vs. inactive/sedentary (<150 min/week/>8h/day) ARD. A dose-response was observed, with greater benefits for ≥350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised individuals.

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EFFECTS OF PHYSICAL ACTIVITY ON VASCULAR FUNCTION IN AUTOIMMUNE RHEUMATIC DISEASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Rheumatology ◽

10.1093/rheumatology/keab094 ◽

2021 ◽

Author(s):

Tiago Peçanha ◽

Daniel Bannell ◽

Sofia Mendes Sieczkowska ◽

Nicola Goodson ◽

Hamilton Roschel ◽

...

Keyword(s):

Physical Activity ◽

Clinical Trials ◽

Blood Flow ◽

Rheumatic Diseases ◽

Skin Blood Flow ◽

Vascular Function ◽

Meta Analysis ◽

Aortic Pulse Wave Velocity ◽

Pharmacological Management ◽

Autoimmune Rheumatic Diseases

Abstract Objectives To summarise existing evidence and quantify the effects of physical activity on vascular function and structure in autoimmune rheumatic diseases (ARDs). Methods Databases were searched (up to March 2020) for clinical trials evaluating the effects of physical activity interventions on markers of micro- and macrovascular function and macrovascular structure in ARDs. Studies were combined using random-effects meta-analysis, which was conducted using the Hedge's g. Meta-analyses were performed on each of the following outcomes: (1) microvascular function (i.e., skin blood flow or responses to acetylcholine [ACh] or sodium nitropusside [SNP] administration); (2) macrovascular function (i.e., brachial flow-mediated dilation [FMD%] or brachial responses to glyceryl trinitrate [GTN%]; and (3) macrovascular structure (i.e., aortic pulse wave velocity [PWV]). Results Ten studies (11 trials), with a total of 355 participants, were included in this review. Physical activity promoted significant improvements in micro- (skin blood flow responses to ACh [g = 0.92; 0.42 to 1.42]) and macrovascular function (FMD% [g = 0.94; 0.56 to 1.02]; GTN% [g = 0.53; 0.09 to 0.98]). Conversely, there was no evidence for beneficial effects of physical activity on macrovascular structure (PWV [g = -0.41; -1.13 to 0.32]). Conclusions Overall, the available clinical trials demonstrated a beneficial effect of physical activity on markers of micro- and macrovascular function, but not on macrovascular structure, in patients with ARDs. The broad beneficial impact of physical activity across the vasculature identified in this review support its role as an effective non-pharmacological management strategy for patients with ARD.

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Physical Activity Associates with Greater Antibody Persistence through 6 Months after the Second Dose of CoronaVac in Patients with Autoimmune Rheumatic Diseases

10.21203/rs.3.rs-1202511/v1 ◽

2021 ◽

Author(s):

Bruno Gualano ◽

Ítalo R. Lemes ◽

Rafael Silva ◽

Ana Jessica Pinto ◽

Bruna Mazzolani ◽

...

Keyword(s):

Physical Activity ◽

Rheumatic Diseases ◽

Neutralizing Antibodies ◽

Vigorous Physical Activity ◽

Geometric Mean ◽

Dose Schedule ◽

Physically Active ◽

Autoimmune Rheumatic Diseases ◽

Antibody Persistence ◽

Active Patients

Abstract This study aimed to investigate the association between physical activity and persistent anti-SARS-CoV-2 antibodies 6 months after two-dose schedule of CoronaVac in autoimmune rheumatic diseases (ARD) patients. This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial (clinicaltrials.gov #NCT04754698), conducted at a tertiary referral hospital in Sao Paulo, Brazil. ARD patients aged ≥18 underwent a two-dose schedule of CoronaVac (Sinovac Life Sciences, China). Persistent immunogenicity 6 months after the full-course vaccination was assessed using seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), and frequency of positive neutralizing antibodies (NAb). Physical activity was assessed trough questionnaire (active being defined as ≥150 min/week of moderate-to-vigorous physical activity). Physically active (n=421) and inactive (n=327) ARD patients were similar for most characteristics; however, active patients were significantly younger (p<0.001), had less chronic inflammatory arthritis (p<0.001) and less frequently used biologic agents (p<0.001) than inactive ones. Six months after full-course vaccination, being male (p<0.001), use of prednisone (p<0.01) and biologics (p<0.001) were associated with poor immunogenicity, while being physically active was associated with better humoral response (p<0.01). Adjusted point estimates from logistic regression models indicated greater odds of seroconversion rates (OR: 1.5 [95%CI: 1.1 to 2.1]) and NAb positivity (OR: 1.5 [95%CI: 1.0 to 2.1]) in physically active patients and approximately 43% greater GMT (42.8% [95%CI: 11.9 to 82.2]) than inactive ones. In conclusion, among immunocompromised patients, being physically active was associated with an increment in antibody persistence through 6 months after a full-course of an inactivated SARS-CoV-2 vaccine.

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EVALUATION OF ANTI-DFS70 ANTIBODIES PRE-ABSORPTION PROTOCOL FOR ANA-IIF HEP-2 TESTING IN THE DIAGNOSTIC APPROACH OF SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES

10.26226/morressier.56e174dbd462b8028d88ad4c ◽

2016 ◽

Author(s):

Alexandra Tsirogianni

Keyword(s):

Rheumatic Diseases ◽

Diagnostic Approach ◽

Autoimmune Rheumatic Diseases

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TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-019-0043-0 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Manal Y. Tayel ◽

Aida Nazir ◽

Ibtessam M. Abdelhamid ◽

Myriam A. S. Helmy ◽

Nadia E. Zaki ◽

...

Keyword(s):

Risk Factors ◽

Rheumatic Diseases ◽

Lymphoproliferative Disorders ◽

Group Iii ◽

Autoimmune Rheumatic Diseases ◽

Group I ◽

Tnf Α ◽

Ifn Γ ◽

Tgf Β1 ◽

Distribution Frequency

Abstract Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

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P052 Leflunomide and severe COVID-19 outcome: a cautionary observation from the COVID-19 Scottish Registry of Autoimmune Rheumatic Diseases (SCAR-19)

Rheumatology ◽

10.1093/rheumatology/keab247.049 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Maira Karabayas ◽

James Brock ◽

Gillian Fordyce ◽

Neil Basu

Keyword(s):

Rheumatic Diseases ◽

Clinical Characteristics ◽

National Registry ◽

Favourable Outcome ◽

Non Invasive ◽

Autoimmune Rheumatic Diseases ◽

Non Invasive Ventilation ◽

Pcr Diagnosis ◽

Related Symptom ◽

Disease Modifying

Abstract Background/Aims Leflunomide, a conventional disease modifying drug (csDMARD), is used in a variety of autoimmune rheumatic diseases (ARD) due to its immunomodulating, immunosuppressive and antiproliferative properties. This agent does however confer a greater infection risk and, due to its long half-life, drug washout procedures are often advised in the context of serious infections. Interestingly, Leflunomide is currently being tested as a potential therapy for COVID-19 in the general population. It is unknown whether leflunomide therapy is associated with a poor or favourable outcome among ARD patients infected with COVID-19. Methods A Scottish-wide registry was rapidly developed in March 2020. Clinical characteristics and outcomes of infected cases were collated across all Scottish health boards. Eligible patients included any adult leflunomide treated ARD patients with a confirmed (clinically or PCR) diagnosis of COVID-19. Results Of the 69 cases included in the registry, n = 4 were treated with leflunomide (75% female; mean age 61, SD 4.2). N = 2 were treated with combination baricitinib or hydroxychloroquine respectively, whilst n = 1 received recent corticosteroid therapy (intramuscular Kenalog). Comorbidities observed in this sub-cohort include diabetes mellitus n = 3, hypertension n = 2, cardiovascular disease n = 1, lung disease n = 1 and latent TB n = 1. At presentation, all patients (n = 4) experienced the established COVID-19 related symptom triad of dyspnoea, cough and fever and promptly developed acute respiratory syndrome. Diarrhoea was also recorded in n = 2 and constitutional upset n = 3. All patients suffered a serious COVID-19 disease outcome (defined as a requirement of invasive or non-invasive ventilation (n = 4) and/ or death (n = 2). P052 Table 1:Patient demographics, clinical characteristics and outcomesPatient 1Patient 2Patient 3Patient 4Age58635766SexFemaleFemaleMaleFemaleRheumatic diagnosisRheumatoid arthritisPsoriatic arthritisPsoriatic arthritisRheumatoid ArthritisComorbiditiesDiabetesHypertension Diabetes COPDNilIschaemic heart disease Hypertension Diabetes Latent TBClinical presentationDyspnoea Cough Fever Confusion Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetDyspnoea Cough Fever Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetAdditional csDMARD*NilNilNilHydroxychloroquinebDMARD**/ tsDMARD***BaricitinibNilNilNilSteroid therapyNilNilNilIM KenalogInvasive or non-invasive ventilationYesYesYesYesDeathNoNoYesYes* conventional disease modifying drug,**biologic disease modifying drug,***targeted synthetic disease modifying drug. Conclusion Preliminary data from this Scotland-wide registry has identified only a small number of leflunomide treated ARD patients infected with COVID-19. However, it is concerning that all cases experienced a serious outcome. Given the relatively infrequent prescription of this drug, combining similar national registry data is necessary to ensure this observation is not spurious. If confirmed, leflunomide washout procedures should be encouraged among such patients when they first present with COVID-19. Disclosure M. Karabayas: None. J. Brock: None. G. Fordyce: None. N. Basu: None.

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AB1336-HPR NON-PHARMACOLOGIC TOPICS RELEVANT FOR CLINICAL RESEARCH IN RHEUMATIC DISEASES: THE PATIENT PERSPECTIVE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.700 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1956.2-1956

Author(s):

F. Ingegnoli ◽

T. Schioppo ◽

T. Ubiali ◽

S. Ostuzzi ◽

M. Buoli ◽

...

Keyword(s):

Physical Activity ◽

Clinical Research ◽

Environmental Pollution ◽

Rheumatic Diseases ◽

Social Life ◽

Eating Habits ◽

Well Being ◽

Psychological Well Being ◽

Work Activity ◽

Patients Perspective

Background:The research approach on Rheumatic diseases (RDs) is challenging and patient involvement as partners in medical research is an emerging force to obtain relevant information and to add unique skills, values and experiences to research. Despite growing interest in non-pharmacologic aspects of clinical research in RDs, the patients’ perspective is currently poorly explored.Objectives:To identify and rank the priorities for clinical research according to patients’ perspective.Methods:A structured face-to-face meeting between physicians and a patient representative was convened to list the non-pharmacologic topics relevant to RD patients. A cross-sectional no-profit on-line anonymous survey was devised to evaluate opinions of RD patients. They were asked to rate the following topics: food/nutrition, air pollution, smoking, work activity, social participation, physical activity, emotional well-being/stress, alternative medicine, and patient-physician relationship. Moreover, patients were asked to explain for which reason a topic was considered important (disease prevention, halting disease progression, symptoms control and disease cure). The survey was disseminated by ALOMAR (Lombard Association for Rheumatic Diseases) between June and October 2019.Results:200 rheumatic patients completed the survey: 130 inflammatory arthritis, 50 connective tissue diseases/vasculitis, and 20 among osteoarthritis, gout, condrocalcinosis, polymyalgia and primary fibromyalgia. Respondents were 178 female with median age of 50 years and median disease duration of 7 years. Among the nine topics identified, the one most rated by patients was the doctor-patient relationship; 188 (94%) of respondents considered this topic very or extremely important (see table below). In descending order, patients rated very or extremely important: psychological well-being/stress 185 (92.5%), physical activity 155 (77.5%), nutrition, eating habits and alcohol 150 (75%), alternative therapies 144 (72%), work activity 144 (72%), environmental pollution 134 (67%), social life 121 (60.5%) and cigarette smoke 119 (59.5%). The topics considered relevant was perceived to be able to influence disease symptoms. Regarding RD prevention, environmental pollution and cigarette smoking were considered the most important topics, while fewer patients believed that research on other topics could help to stop disease progression or to achieve disease healing.RankingTopicNot or quite importantVery or extremely important1Doctor-patient relationship, n (%)12 (6.0)188 (94.0)2Psychological well-being/stress, n (%)15 (7.5)185 (92.5)3Physical activity, n (%)45 (22.5)155 (77.5)4Nutrition/eating habits/alcohol, n (%)50 (25.0)150 (75.0)5Alternative therapies, n (%)56 (28.0)144 (72.0)6Work activity, n (%)56 (28.0)144 (72.0)7Environmental pollution, n (%)66 (33.0)134 (67.0)8Social life, n (%)79 (39.5)121 (60.5)9Cigarette smoke, n (%)81 (40.5)119 (59.5)Conclusion:This survey highlights the relevance of several unmet needs. The holistic approach, in terms of medical consultation and psychological well-being, is considered the most important component able to influence disease perception. By capturing patient opinions on non-pharmacological topics for clinical research, this survey indicates that the active patient involvement is essential to design successful translational studies and improve clinical outcomes.Acknowledgments:We thank the Lombard Association of Rheumatic Diseases (ALOMAR) for its contribution to plan and disseminate the survey and the group that sustain systemic sclerosis (GILS).Disclosure of Interests:Francesca Ingegnoli: None declared, Tommaso Schioppo: None declared, Tania Ubiali: None declared, Silvia Ostuzzi: None declared, Massimiliano Buoli: None declared, Valentina Bollati: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

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