Age Related Differences in Monocyte Subsets and Cytokine Pattern during Acute COVID-19—A Prospective Observational Longitudinal Study

The COVID-19 pandemic drastically highlighted the vulnerability of the elderly population towards viral and other infectious threats, illustrating that aging is accompanied by dysregulated immune responses currently summarized in terms like inflammaging and immunoparalysis. To gain a better understanding on the underlying mechanisms of the age-associated risk of adverse outcome in individuals experiencing a SARS-CoV-2 infection, we analyzed the impact of age on circulating monocyte phenotypes, activation markers and inflammatory cytokines including interleukin 6 (IL-6), IL-8 and tumor necrosis factor (TNF) in the context of COVID-19 disease progression and outcome in 110 patients. Our data indicate no age-associated differences in peripheral monocyte counts or subset composition. However, age and outcome are associated with differences in monocyte activation status. Moreover, a distinct cytokine pattern of IL-6, IL-8 and TNF in elderly survivors versus non-survivors, which consolidates over the time of hospitalization, suggests that older patients with adverse outcomes experience an inappropriate immune response, reminiscent of an inflammaging driven immunoparalysis. Our study underscores the value, necessity and importance of longitudinal monitoring in elderly COVID-19 patients, as dynamic changes after symptom onset can be observed, which allow for a differentiated insight into confounding factors that impact the complex pathogenesis following an infection with SARS-CoV-2.

Clustering fibromyalgia patients: A combination of psychosocial and somatic factors leads to resilient coping in a subgroup of fibromyalgia patients

Background Coping strategies and their efficacy vary greatly in patients suffering from fibromyalgia syndrome (FMS). Objective We aimed to identify somatic and psychosocial factors that might contribute to different coping strategies and resilience levels in FMS. Subjects and methods Standardized questionnaires were used to assess coping, pain, and psychological variables in a cohort of 156 FMS patients. Quantitative real-time polymerase chain reaction (qRT-PCR) determined gene expression of selected cytokines in white blood cells of 136 FMS patients and 25 healthy controls. Data of skin innervation, functional and structural sensory profiles of peripheral nociceptive nerve fibers of a previous study were included into the statistics. An exploratory factor analysis was used to define variance explaining factors, which were then included into cluster analysis. Results 54.9% of the variance was explained by four factors which we termed (1) affective load, (2) coping, (3) pain, and (4) pro-inflammatory cytokines (p < 0.05). Considering differences in the emerged factors, coping strategies, cytokine profiles, and disability levels, 118 FMS patients could be categorized into four clusters which we named “maladaptive”, “adaptive”, “vulnerable”, and “resilient” (p < 0.05). The adaptive cluster had low scores in disability and in all symptom categories in contrast to the vulnerable cluster, which was characterized by high scores in catastrophizing and disability (p < 0.05). The resilient vs. the maladaptive cluster was characterized by better coping and a less pro-inflammatory cytokine pattern (p < 0.05). Conclusion Our data suggest that problem- and emotion-focused coping strategies and an anti-inflammatory cytokine pattern are associated with reduced disability and might promote resilience. Additional personal factors such as low anxiety scores, ability of acceptance, and persistence further favor a resilient phenotype. Individualized therapy should take these factors into account.

Clustering fibromyalgia patients: A combination of psychosocial and somatic factors leads to resilient coping in a subgroup of fibromyalgia patients

Background: Coping strategies and their efficacy vary greatly in patients suffering from fibromyalgia syndrome (FMS). Objective: We aimed to identify somatic and psychosocial factors that might contribute to different coping strategies and resilience levels in FMS. Subjects and methods: Standardized questionnaires were used to assess coping, pain, and psychological variables in a cohort of 156 FMS patients. Quantitative real-time polymerase chain reaction (qRT-PCR) determined gene expression of selected cytokines in white blood cells of 136 FMS patients and 25 healthy controls. Data of skin innervation, functional and structural sensory profiles of peripheral nociceptive nerve fibers of a previous study were included into the statistics. An exploratory factor analysis was used to define variance explaining factors, which were then included into cluster analysis. Results: 54.9% of the variance was explained by four factors which we termed (1) affective load, (2) coping, (3) pain, and (4) pro-inflammatory cytokines (p < 0.05). Considering differences in the emerged factors, coping strategies, cytokine profiles, and disability levels, 118 FMS patients could be categorized into four clusters which we named maladaptive, adaptive, vulnerable, and resilient (p < 0.05). The adaptive cluster had low scores in disability and in all symptom categories in contrast to the vulnerable cluster, which was characterized by high scores in catastrophizing and disability (p < 0.05). The resilient vs. the maladaptive cluster was characterized by better coping and a less pro-inflammatory cytokine pattern (p < 0.05). Conclusion: Our data suggest that problem- and emotion-focused coping strategies and an anti-inflammatory cytokine pattern are associated with reduced disability and might promote resilience. Additional personal factors such as low anxiety scores, ability of acceptance, and persistence further favor a resilient phenotype. Individualized therapy should take these factors into account.

AB0036 CHILDREN WITH EXTENDED OLIGOARTICULAR AND POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS HAVE A CYTOKINE PATTERN FAVOURING B CELL ACTIVATION IN CIRCULATION

Background:Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The majority of polyarticular JIA (pJIA) and a large fraction of extended oligoarticular JIA (oJIA) patients fulfil classification criteria for rheumatoid arthritis (RA) in adulthood. B-cells play several important roles in RA pathogenesis, but it is still unclear if the pattern of B-cell involvement in pJIA and extended oJIA follows what has been described for adults with RA.Objectives:The main goal of this study was to determine the concentration of cytokines potentially relevant for B-cell activation in serum from children with pJIA and extended oJIA when compared to children with persistent oJIA, adult JIA, early and established RA.Methods:Serum samples were collected from children with extended oJIA (n=8), persistent oJIA (n=6), pJIA (n=6), adult JIA (n=8), untreated early RA (<1 year of disease duration, n=12), established RA patients treated with synthetic disease-modifying anti-rheumatic drugs (DMARDs) (n=10) and two groups of age- and sex-matched healthy donors (children, n=6 and adults, n=10). A proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF), interleukin (IL)-6 and IL-21 serum levels were measured by enzyme-linked immunosorbent assay (ELISA).Results:Children with extended oJIA, early and established RA patients had significantly higher BAFF serum levels when compared to controls, but no significant differences were observed in children with persistent oJIA, pJIA and adult JIA when compared to all groups included. APRIL serum levels were significantly increased in early and established RA patients when compared to both controls and children with persistent oJIA. No significant differences were found in APRIL concentrations between children with JIA, adult JIA and controls. IL-6 serum levels were significantly increased in children with extended oJIA, pJIA, early and established RA when compared to controls, but no significant differences were found in children with persistent oJIA and adult JIA patients. IL-21 serum levels were significantly increased in early RA when compared to controls, but no significant differences were observed between any of the other groups included.Conclusion:The similarity in B-cell cytokine pattern found between extended oJIA, pJIA, early and established RA patients, contrarily to what was observed in persistent oJIA, suggests an early B-cell involvement in the pathogenesis of extended oJIA and pJIA as described for RA.Disclosure of Interests:None declared