Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19.

Introduction: Although the phenomenon of cytokine storm is well described in patients with severe COVID-19, little is known about the role of the immune system in asymptomatic patients, especially in the group with autoimmune diseases, such as inflammatory bowel disease (IBD). Aim: To assess the stimulation of the immune system expressed through the production of cytokines in IBD patients with asymptomatic COVID-19. Material and methods: This is a multi-centre, prospective study in which the concentration of many cytokines (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL- 15, IL-17, IL-23, IFN-γ, TNF-α, TNF-ß) was assessed in patients with IBD and asymptomatic SARS-CoV-2 infection diagnosed by serological tests. Results: In the group of patients with a recent SARS-CoV-2 infection, defined as positive antibodies in the IgA + IgM class, a higher percentage of patients with the presence of interleukin (IL) 2 (IL-2) was found. No association with other cytokines or effects of IBD activity or treatment was found. However, the effect of the applied treatment on the concentration of some cytokines was found: a negative association of infliximab, vedolizumab, and prednisone with IL-2, a positive correlation of steroids, thiopurines with IL-10, and in the case of tumor necrosis factor-α (TNF-α), negative with infliximab, and positive with vedolizumab. Conclusions: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.

The persistence of SARS-CoV-2 neutralizing antibodies after COVID-19: A one-year observation. Is a SARS-CoV-2 vaccination booster dose necessary?

Introduction: The aim of this study was to investigate the persistence of SARS-CoV-2 neutralizing antibodies (NAbs) one year after contracting COVID-19. Material and methods: The study included 38 patients - 34 men and 4 women - suffering from COVID-19 between March 15 and May 26, 2020. The median age in the group was 31 years, ranging from 22 to 67 years. The levels of neutralizing antibodies were measured at three time-points - baseline, 6 months, and 12 months. The primary endpoint was a post-infection positive result for NAbs (> 15 AU/ml; Liaison SARS-CoV-2 S1/S2 IgG quantitative test) 12 months after infection. Results: The median level of NAbs after 12 months was 26.5 AU/ml. At the end of observation (12 months), 21 of the 38 patients had a NAb level of >15 AU/ml (positive). The median antibody half-life was 5.8 months. Conclusions: A high percentage of the patients maintained positive levels of antibodies 6 and 12 months after COVID-19 infection. The dynamics of the antibody level decline suggests the need for booster vaccination at least once a year.

Effect of Intravenous Iron Administration on Bone Mineral and Iron Homeostasis in Patients with Inflammatory Bowel Disease-Results of a Prospective Single-Centre Study.

INTRODUCTION: Anaemia and bone metabolism alterations are common in inflammatory bowel disease (IBD), which is a heterogeneous group of diseases that include Crohn's disease (CD) and ulcerative colitis (UC) with a rich intestinal and extraintestinal symptomatology. All these make the diagnostic procedures complicated and difficult. PURPOSE AND SCOPE: The aim of this study was to assess the effect of parenteral iron administration on biomarkers of mineral and bone homeostasis over time. MATERIALS AND METHODS: The study was a single-centre non-randomised prospective study. It was carried out between 2016 and 2020 in a group of patients in the Department of Internal Medicine and Gastroenterology Subunit of Inflammatory Bowel Diseases at the National Institute of Medicine of the Ministry of the Interior and Administration in Warsaw. At the first examination, the baseline disease severity, initial evaluation of anaemia (morphology, iron (Fe), total iron binding capacity (TIBC), ferritin, vitamin B12, folic acid) and bone mineral metabolism including C-reactive protein (CRP), albumins, alkaline phosphatase (ALP), Calcium, osteocalcin, phosphate in serum and in urine, parathyroid hormone (PTH), vitamin D3, fibroblast growth factor (iFGF23) and procollagen type 1N propeptide (P1NP) C-terminal telopeptide (CTX), was initially assessed. On the basis of peripheral blood counts, an appropriate dose of iron (iron derisomaltose or caboxymaltose) was administered. During the subsequent appointments on week 1, 4, and 12 morphology, iron (Fe), total iron binding capacity (TIBC), ferritin, vitamin B12, folic acid, C-reactive protein (CRP), albumins, alkaline phosphatase (ALP), Calcium, osteocalcin, phosphate in serum and in urine, parathyroid hormone (PTH), vitamin D3, fibroblast growth factor (iFGF23) and procollagen type 1N propeptide (P1NP) C-terminal telopeptide (CTX), were evaluated. RESULTS: A total of 56 patients were enrolled into the study: 24 women and 32 men. In the group, 32 patients had Crohn's disease (CD) and 24 had ulcerative colitis (UC). We found a statistically significant increase in the concentration of albumin (p = 0.031), haemoglobin (p < 0.001), haematocrit (p < 0.001), MCV (p < 0.001), MCHC (p = 0.001), iron (p < 0.001) and ferritin (p < 0.001) after the administration of parenteral iron. The influence of individual iron formulations on the analysed parameters (phosphate concentration in serum and in the urine, iFGF23, P1NP, PTH, vitamin D, haemoglobin and ferritin) was similar. Interestingly, an inverse correlation was found between the concentration of phosphorus in the blood and iFGF23 at certain time-points; however, in the study group they did not significantly affect the disturbances of calcium and phosphate metabolism. CONCLUSIONS: In the study group, transient and non-significant disorders of phosphate metabolism were found, which does not constitute a contraindication to treatment with parenteral iron in inflammatory bowel disease patients, which was safe and efficient.

Social Distancing during COVID-19 Pandemic among Inflammatory Bowel Disease Patients.

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study included 473 patients with IBD who made 1180 hospital visits from 1 May to 30 September 2020. During each visit, the patients completed a five-step, progressive scale that was developed to assess the degree of social isolation. In parallel, other demographic data were collected and the concentrations of anti-severe acute respiratory coronavirus 2 (SARS-CoV-2) IgG and IgM+IgA antibodies were measured using the ELISA method. (3) Results: The study found a significant correlation between the degree of social distancing and the presence of anti-SARS-CoV-2 antibodies in the groups with the lowest degree of isolation (3 to 5). (4) Conclusions: Maintaining social distancing is an effective method for reducing the spread of SARS-CoV-2 virus among IBD patients.

Convalescent plasma treatment is associated with lower mortality and better outcomes in high-risk COVID-19 patients - propensity-score matched case-control study.

OBJECTIVE: This study aimed to investigate the efficacy and safety of convalescent plasma (CP) transfusion in a group of high-risk COVID-19 patients. METHODS: This prospective study included 204 patients from a single tertiary-care hospital, hospitalized with COVID-19, of whom 102 were treated with CP administration and standard care (PG) and 102 others who received standard care only (CG). The CG was selected from 336 hospitalized patients using the propensity-score matching (PSM) technique using age, MEWS score, and comorbidities. The primary outcome was mortality rate; secondary outcomes were the requirement of a ventilator, length of ventilator need, length of intensive care unit (ICU) stay, and length of overall hospital confinement. Additionally, parameters predicting death in COVID-19 patients were identified. RESULTS: Findings confirmed a significantly lower mortality rate in the PG versus the CG (13.7% vs. 34.3 %, p = 0.001) and a significant difference in the cumulative incidence of death between the two groups (p < 0.001). CP treatment was associated with lower risk of death (OR = 0.25 CI95 [0.06; 0.91], p = 0.041). There were no significant differences in ICU stay, ventilator time, and hospitalization time between the two groups. CONCLUSIONS: A significantly lower mortality rate was observed in the group of patients treated with CP. Age, presence of cardiac insufficiency, active cancer, a ventilator requirement, and length of hospitalization significantly increased the risk of death in both groups. Our study shows that CP affords better outcomes when administrated in the earlier stage of high-risk COVID-19 disease.

Inflammatory bowel disease is associated with higher seroprevalence rates of antibodies against SARS-CoV-2.

INTRODUCTION: According to the current data, there has been no increase in the incidence of COVID­19 in patients with inflammatory bowel disease (IBD). OBJECTIVES: The available data are based on symptomatic cases and do not include the asymptomatic ones. To measure the exact infection rate, we initiated a study that aimed to assess the seroprevalence of anti-SARS­CoV­2 antibodies in IBD. PATIENTS AND METHODS: A total of 864 individuals were enrolled in the study, including 432 patients with IBD (290 with Crohn disease and 142 with ulcerative colitis) and 432 controls without IBD (healthcare professionals) matched for age and sex. Serum samples were prospectively collected, and the presence of anti-SARS­CoV­2 immunoglobulin (Ig) G and IgM + IgA antibodies were measured using the enzyme­linked immunoassay method (Vircell Microbiologists). RESULTS: A significantly higher percentage of positive results for anti-SARS­CoV­2 antibodies, both in the IgG and IgM + IgA class, was found in patients with IBD (4.6% and 6%, respectively, compared with 1.6% and 1.1%, respectively, in controls; both P values <0.05). No patient had symptomatic COVID­19. There was no association among patients' age, sex, drugs used for IBD, or disease activity and the occurrence of IgG antibodies. CONCLUSION: Patients with IBD may be at higher risk of developing SARS­CoV­2 infection, defined as the presence of elevated levels of anti-SARS­CoV­2 IgG antibodies, but not of having a symptomatic and / or severe course of COVID­19 compared with healthcare professionals without IBD.

Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP) - Progress in prediction of AP severity.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during inflammation and infections. Moreover, increased levels of suPAR are observed after hypoxia and ischaemia. The aim of the study was to assess whether suPAR could represent a useful marker of acute pancreatitis (AP) severity. PATIENTS AND METHODS: We have observed a cohort of 126 prospectively enrolled patients. Based on the presence of persistent organ failure (more than 48 h) and local complications (diagnosis of moderate AP [MSAP]), patients were classified into three groups: mild AP (MAP), moderate and severe AP (SAP). The blood samples were taken on admission for detecting suPAR concentrations. RESULTS: AP was considered severe in 33 patients (26.2%), MSAP was found in 37 patients (29.4%), and MAP was found in 56 patients (44,4%). The AUC for SAP predicted by suPAR was 0.993. The calculated cut-off point for prognosis SAP is 4.75 ng/mL. The BISAP score of ≥3 for detection of SAP had sensitivity and specificity of 94.6% and 63.6%, respectively. The AUC for severity predicted by BISAP amounted to 0.916. Additionally, suPAR turned out to be a good predictor of fatal AP: for the cut-off point 7.05 ng/mL, the AUC was 0.917. The AUC for death prediction in AP patients based on the BISAP score ≥3 was 0.894. CONCLUSIONS: suPAR concentration is a promising new diagnostic and prognostic indicator in SAP obtainable in the early stage of disease. Larger studies are recommended to evaluate this role further.

Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis.

Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-alpha, IL-1, IL-6) osteoclasts' activation, osteoprotegerin and its ligand's (RANKL) function disorders, patients' immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation--serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler-Rose's test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers' concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers' concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers' concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale's than at more advanced stages. Ctx concentrations decreased with the disease duration. Serum morphogenesis and resorption markers' concentrations change in course of RA indicating the decrease in bone metabolic activity with the disease duration and progression. High RA activity and severity correlate with increased markers' levels-the resorption one. The influence of GCS on bone metabolism in RA requires further study.

Serum leptin in rheumatoid arthritis.

Leptin is a peptide hormone that has an essential role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. The role of leptin in the modulation of the immune response and inflammation has been regarded as important. In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. These features suggest that leptin may also influence the inflammatory mechanisms of arthritis in humans. In this study we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA and 30 OA patients who constituted the control group. Serum leptin level was determined using the DRG Leptin ELISA Kit-a solid phase enzyme-linked immunosorbent assay based on the sandwich principle. The serum level of leptin in RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a positive correlation between body mass index (BMI) of RA patients and serum level of leptin (correlation coefficients Spearman's r = 0.81). According to correlation coefficients, serum leptin level is independent of age of RA patients, stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration as well as value of titre of the Waaler-Rose, disease activity score (DAS 28) value and presence of rheumatoid nodules. There was a negative correlation between serum leptin level and glomerular filtration rate (GFR). No correlation between the serum leptin level and T-score was found. An influence of steroid treatment on the serum leptin level was not shown. The median serum leptin level in OA patients was 9.2 ng/ml. There was a positive correlation between body mass index of OA patients and serum level of leptin (correlation coefficients Spearman's r = 0.57). No correlation was found between serum leptin level and patient's age, duration of disease and value of laboratory data. There were no correlations between serum leptin level and visual analogue pain scale (VAS) for the lower-limb afflicted patients as well as stage of disease according to Kellgren and Lawrence's score in OA patients. There was a negative correlation between serum leptin level and T-score value in OA patients (r = -0.58, P < 0.05). No statistically significant differences were found between serum leptin levels for RA and OA patients.