SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Recent Findings on Platelet Activation, vWF Multimers and Other Thrombotic Biomarkers Associated with Critical COVID-19

Mortality rate in patients with COVID-19 increases in those admitted to the ICU. Activation of the coagulation system is associated with the worse disease outcomes. The aim of this study was to evaluate platelet activation and thrombotic biomarkers in hospitalized patients with COVID-19 during the second and third infection waves of the pandemic during 2021, following a previous report that included patients from the first wave. Sixty five patients were recruited and classified according to disease outcome;10 healthy donors were included as a control group. Among prothrombotic biomarkers, t-PA concentrations (p < .0001), PAI-1 (0.0032) and D dimer (p = .0011) were higher in patients who developed critical COVID-19. We also found platelet activation via alpha IIb beta III expression (p < .0001) and higher presence of vWF-HMWM in severe COVID-19 (p < .0001). Several prothrombotic biomarkers are found to be increased since hospital admission in patients which lately present a worse disease outcome (ICU admission/death), among these, platelet activation, vWF increased plasma concentration and presence of HMWM seem to be of special interest. New studies regarding the predictive value of thrombotic biomarkers are needed as SARS-CoV-2 variants continue to emerge.

Analysis of anxiety in the Covid-19 pandemic

This article aims to analyze anxiety in adults from Quito, Ecuador;The sample consisted of 135 men and women between the ages of 18 and 73 who had not presented a previous diagnosis of anxiety. The Beck Anxiety Inventory (BAI) was applied and it was identified that 14% of the participants present severe anxiety, 17% moderate, 36% minimal and 33% mild, with young people presenting the highest level of severe anxiety compared to adults. In relation to physical and emotional symptomatology, concern, fear and sleep difficulties are considered. © GKA Ediciones, authors.

Platelet reactivity to SARS-CoV- 2 Spike protein and domains

Background: COVID-19 has affected millions of people worldwide over the past two years. SARS-CoV- 2 uses the Spike (S) protein to infect target cells. An active immunothrombotic state has been described in severe stages of infection. Platelets are cells implicated in the pathophysiology of CoVID-19, presumably by contributing to the release of inflammatory cytokines and exhibiting a procoagulant phenotype, although the platelet response in the disease has been studied, information on the cellular response to S protein domains is scarce. Aim(s): To study platelet reactivity response to SARS-CoV- 2 virus Spike protein and RBD domain. Method(s): Blood samples were obtained from healthy volunteers by venipuncture after signing an informed consent form, using 3.2% sodium citrate as anticoagulant. Platelet-rich plasma (PRP) was obtained by slow centrifugation (100 g x 10 minutes). PRP was separated and resuspended in Tyrodes buffer. Platelet stimulation kinetics (1X107 cells/ml) was performed with S full protein and protein S receptor binding domain (RBD) [2 mug/ml], 37degreeC. PRP was also incubated with plasma from COVID-19 patients [20 mul] for different times. Platelet activity was assessed by flow cytometry: CD41-PECy7, CD62-PE and PAC1-FITC. We used ADP 20muM, collagen 0.19 mg/ml and epinephrine 100muM as platelet activation controls. Result(s): We observed platelet reactivity after stimulation with protein S, highest activation was observed at 90 min with full protein and at 120 min with RBD domain when compared to the basal expression of selected markers and is similar to the observed with the positive control agonists. Stimulation of PRP with plasma from COVID-19 patients show the presence of activation markers at 60 min. However, activation is lower than that observed with known activation agonists. Conclusion(s): There is platelet reactivity to Spike protein, the RBD domain and with plasma from COVID-19 affected subjects.

First report and genome sequencing of SARS-CoV-2 in a cat (Felis catus) in Colombia

Introduction. SARS-CoV-2 is a virus of zoonotic origin that can bind to ACE2 receptors on the cells of various mammals, including animals such as cats, dogs, ferrets, hyenas, coatis, otters, big cats, non-human primates, white-tailed deer, manatees, hippopotamuses, hamsters, and minks. Studies have shown that the virus can circulate among minks and Syrian hamsters, mutate, lead to animal-to-human zoonotic jump, and further onward spread between humans. The transmission of the virus from humans to cats is evident, but the virus's return to humans has not yet been demonstrated. Infection in pets is unusual, and there are few human-to-pet transmission reports worldwide. Objective. To describe the SARS-CoV-2 infection in Cordoba, Colombian Caribbean, a domestic animal. Methods. A cross-sectional molecular surveillance study was carried out, oral and rectal swabs were taken from cats and dogs living with people diagnosed with COVID-19. Results. SARS-CoV-2 was found in a cat living with a person with COVID-19. Genome sequencing showed that the B.1.111 lineage caused the infection in the cat. The owner's sample could not be sequenced. The lineage is predominant in Colombia, and this variant is characterized by the presence of the D614D and Q57H mutation. Conclusion.This is the first report on sequencing the SARS-CoV-2 genome in a cat in Colombia shows the importance of some interesting SARS-CoV-2 mutations in promoting the transmissibility of this new coronavirus in companion animals. Lack of information Human-to-cat or cat-to-human infection. © 2022, Fundacao Oswaldo Cruz. All rights reserved.

Neuroimage and autonomic abnormalities in patients with CoVID-19 happy hypoxemia

Objective: To describe the autonomic and SNC manifestations of patients with coronavirus disease 2019 (COVID-19) and happy hypoxemia. Background: Happy hypoxemia is the absence of dyspnea despite low oxygen saturation. Several hypotheses for its occurrence include potential viral neuroinvasion, autonomic dysfunction, and cortical ischemic damage. Design/Methods: We studied prospectively nine patients with COVID-19 who arrived at the ER with very low oxygen saturation (50-79%) and no dyspnea complaints. Patients were invited to participate and underwent a full clinical history, brain MRI with gadolinium, and 24H-Holter with spectroscopy while hospitalized and bed-ridden. We used Pearson's coefficient correlation for the correlation analysis. Results: Two patients were excluded from the study because they no longer wished to participate and one because he had FA. we analyzed six patients (66% women) with a mean age of 59 years old (47-83). Two patients had high blood pressure, one patient had a history of tuberculosis, and one had Down Syndrome. Upon arrival at the ER, the mean oxygen saturation was 67% and PaO2 59.3 (47-83). One patient (14%) complain of headache and none of anosmia or ageusia. Four patients underwent a brain MRI that showed gadolinium enhancement of the olfactory bulbs and white matter lesions. One patient also had a left insular lesion. Three patients had abnormal SDNN<100 (83ms, 30-146), and one had RMSSD <15. Vagally mediated changes reflected in HRv were significantly lower in patients with lower blood O2 saturation (SDDN p=0.002, r=.95, HF p=0.009, r=.92, LF/HF ns, -0.42). Conclusions: Patients with happy hypoxemia had decreased heart rate variability that correlated with the degree of hypoxemia, suggesting altered modulation of vagal tone and autonomic dysregulation. All the patients had olfactory bulb enhancement. In our patients, hyposmia /anosmia did not correlate with olfactory bulb hyperintensities or happy hypoxemia.

Telephone-based mindfulness training in diverse prehypertensive women: Results of a pilot randomized controlled trial

Introduction: Chronic stress is associated with incident hypertension and is a promising intervention target for lowering blood pressure (BP), particularly in women. Growing evidence suggests that mindfulness-based interventions can reduce BP and improve psychological outcomes but the in-person format of traditional programs limits access. The goal of this study was to evaluate the feasibility, acceptability and effects of telephone-delivered mindfulness-based cognitive therapy (MBCT-T) in women with prehypertension. Methods: We conducted a pilot RCT in which 37 women meeting JNC 7 criteria for prehypertension (SBP 120-139 mmHg or DBP 80-89 mmHg) and not taking antihypertensive medication were recruited from outpatient clinics or via the EHR. Eligible participants were randomized to usual care or MBCT-T, which involved 8 weekly 1-hour phone sessions delivered to small groups by a trained instructor. Outcomes included feasibility (session completion), acceptability (Client Satisfaction Questionnaire [CSQ]), SBP (mean of 3 clinic BP measurements), perceived stress (PSS-10) and depressive symptoms (PHQ-8). Linear mixed models with a random effect of intervention cohort were performed to compare 3-month changes in outcomes between study arms, adjusting for age and ethnicity. Results: The mean age was 50.7±17.7, 68% of participants were racial/ethnic minorities, and baseline SBP/DBP was 127.8±6.2/77.5±7.2 mmHg. There were no significant differences between study arms in demographics or baseline characteristics. The median number of sessions completed was 6 of 8. Fewer sessions were completed by employed vs. unemployed women (4.5 vs. 7.8,t=3.55, p=.003) and by foreign-born vs. U.S.-born women (2.8 vs. 5.9, t=1.87, p=.08). Overall 3-month retention was 89% but follow-up BP was missing in ∼50% of participants due to COVID-19research restrictions. Three-quarters of MBCT-T participants reported high satisfaction with theintervention (CSQ24). In the subgroup with complete follow-up data, SBP declined in both studyarms but there was no significant between-group difference (p=0.51). Conversely, greater reductionsin perceived stress and depressive symptoms were observed in the MBCT-T arm vs. usual care(between-group differences of 3.63 [PSS-10;p=.163] and 2.90 [PHQ-8;p=.008]). In per-protocolanalyses limited to MBCT-T participants who completed ≥4 sessions, effects were larger forperceived stress and similar for depressive symptoms (between-group differences of 6.17 [PSS-10;p=.012] and 2.77 [PHQ-8;p=.025]). Conclusions: Results support the feasibility and acceptability of telephone-based mindfulnesstraining in diverse women with prehypertension. Promising findings for stress and depressivesymptoms suggest further studies are warranted. Strategies to address barriers to participation, particularly among working women and minorities, are needed.

Efficacy of the Mechanistic Score and COVID-19 Mortality Risk scales to assess the risk of mortality in patients hospitalized for COVID-19

Introduction: Chronic diseases are associated with a higher risk of mortality from COVID-19. Objective: To compare the efficacy of the Mechanistic Score and COVID-19 Mortality Risk scales for assessing the risk of mortality in patients hospitalized for COV-ID-19. Methods: Comparative, observational, retrospective study. The mortality rate of COVID-19-positive patients was assessed by comparing both scales, according to information obtained from the records of patients hospitalized for COVID-19 in a specialty hospital. Results: Two-hundred and twenty-one patients were evaluated, out of whom 61% were men and 39% were women;89% had comorbidity: obesity (88%), hypertension (40%), diabetes mellitus (31%) and cancer (6%). At discharge, 65% survived. The COVID-19 Mortality Risk scale showed a sensitivity of 79% and specificity of 88% for predicting mortality risk. In patients with low risk, the Mechanistic Score showed a sensitivity and specificity of 24 and 97%, respectively;in cases with mild risk, 44 and 97%;with moderate risk, 57 and 77%;with high risk, 95 and 91%;and with remarkably high risk, 100 and 100%. Conclusion: The COVID-19 Mortality Risk scale has higher efficacy than the Mechanistic Score for assessing mortality risk in patients with COVID-19. © 2022 Academia Nacional de Medicina de México, A.C. Publicado por Permanyer.