ANTI-TNF TREATMENT MODIFIES PAIN MODULATION DESCENDING PATHWAYS. A PROSPECTIVE, 6 MONTHS STUDY IN ACTIVE CHRONIC INFLAMMATORY RHEUMATISM PATIENTS' NAÏVE OF BDMARD

BackgroundIn rheumatoid arthritis (RA) and spondyloarthritis (Spa), persistent pain remains challenging. In active disease, diffuse noxious inhibitory controls (assessed through conditioned pain modulation (CPM)) are impaired [1]. Little is known regarding impairment of pain pathways in patients under bMDARD.ObjectivesThe main objective of the RAPID (Rheumatism Pain Inhibitory Descending pathways) study, was to assess descending pain modulation (through CPM paradigm) in patients with active RA or Spa, after introduction of first bDMARD with anti-TNF.MethodsWe included 50 RA and 50 Spa patients with active disease, naïve of bDMARD. We assessed clinical disease variables for patients, together with responses to various psychological questionnaires. All participants underwent QST with the determination of heat and cold pain thresholds (HPT-CPT) on dominant forearm and CPM. CPM paradigm require a conditioning stimulus, here applied to the non-dominant foot (cold circulating bath at 8°C during 1min). Descending pain control was assessed as the change in HPT (in °C) following the conditioning stimulus: the higher the CPM effect, the more efficient the inhibitory control. Patients were followed at 3 and 6 months after TNF inhibitor initiation. At both follow-up visits, clinical monitoring of the rheumatism and repeated thermal QST and CPM.ResultsOne hundred patients were included, 59 women, mean age 45.8 (± 14.6) and mean disease duration 7.93 (± 7.96) years. Due to COVID surge 87 patients initiated an anti-TNF, 74 patients completed the follow-up. At 6 months, 40 patients achieved a good therapeutic response (good EULAR response or ASDAS major improvement), 19 patients had a moderate therapeutic response (moderate EULAR response or clinically important improvement) and 15 patients had no therapeutic response. At the end of follow-up, 51 patients were in remission or low disease activity and 47 patients had a pain intensity <4/10. Thermal pain thresholds did not significantly change during follow-up. Mean HPT was at beaseline 42.35°C (+/- 3.68) and at 6 months 42.17°C (+/- 3.67). Mean CPT was at baseline 13.11°C (+/- 10.04) and at 6 months 12.86°C (+/- 9.45). Conditioned pain modulation was significantly changed during follow-up. Mean CPM effect was at baseline 0.25°C (±2.57), 2.64°C (±2.12) at 3 months and 2.96°C (±2.50) at 6 months. At the end of the 6 months follow-up, mean CPM effect was significantly higher in patients with residual mean pain intensity <4/10 compared to patients with persisting pain ≥ 4/10: 3,25°C (± 2,68) vs 2,47 (± 2,11) (p=0.04).ConclusionAfter TNF inhibitor initiation in active RA or SpA, impaired diffuse noxious inhibitory controls are significantly improved. Apart from their articular efficacy, TNF inhibitor have an action on the central nervous system and pain modulation pathways. In patients with persisting pain under bDMARD, diffuse noxious inhibitory controls are not as efficient as patient without residual pain.Reference[1]Trouvin AP, Simunek A, Coste J, Medkour T, Carvès S, Bouhassira D, Perrot S. Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation. Pain. 2022 Aug 3. doi: 10.1097/j.pain.0000000000002745.Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

The role of government policies for Italian firms during the COVID-19 crisis.

This paper aims to respond to this research question: "How effective have government incentives been in preserving firm profitability and growth during the COVID-19 crisis?". We used a large, representative sample of Italian companies, which has produced a deeper study than the macro analyses provided by national statistics. Results shows that government policies alleviated the negative effects of the pandemic on troubled companies, but it was not enough to maintain the same financial health as firms that did not need this support. Small companies were the most adversely affected by the pandemic.

IDENTIFICATION of KEY BIOMARKERS for the PREDICTION of CRITICAL COVID-19 OUTCOMES

Background: Understanding the role of crucial biomolecules and mechanistic pathways supporting coronavirus disease 2019 (COVID-19) pathophysiology is essential to handle the immune dysregulation and complications driven by uncontrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, we evaluated the proteomics, metabolomics and lipidomics plasma profile in a well-characterized cohort of COVID-19 patients ranging from asymptomatic to critical illness. Methods: This multicenter case-control study enrolled 273 adults with SARS-CoV-2 infection, confirmed by Polymerase chain reaction (PCR), who were recruited within the first 21 days of the infection during the first wave (March-May 2020) of COVID-19 pandemic. Participants were categorized into three groups of severity according to the inclusion criteria described in "Diagnosis and Treatment Protocol for COVID-19 Patients" and distributed as mild (n=77), severe (n=134) and critical (n=62). Serum profile of COVID-19 patients was characterized in the acute phase of the infection using a nontargeted multiomics approach. Univariate and multivariate analyses were performed to identify key molecules involved in critical COVID-19 and to evaluate their predictive power as biomarkers of COVID-19 severity. Results: COVID-19 critically ill patients presented a well-differentiated blood pattern for severe disease. The multiomic analysis identified specific alterations in pathways linked to complement and coagulation cascades, platelet activation, cell adhesion, acute inflammation, energy production (Krebs cycle and Warburg effect), amino acid catabolism and lipid transport as hallmarks of critical COVID-19. A new biomarker panel including the combination of selected proteins, metabolites and lipids predicted with high accuracy the most adverse COVID-19 outcomes (AUC: 0.994, 85.9% specificity and 100% sensitivity). Conclusion: The identification of predictive molecules related to critical COVID-19 outcomes provides a valuable tool for the rapid and efficient identification of clinical worsening in the early stage of SARS-CoV-2 infection. The association of a distinctive proteomic, metabolomic and lipidomic fingerprint with COVID-19 severity provides a better understanding of the immunopathogenesis and the host response to SARS-CoV-2 infection which could help in the identification of potential therapeutic targets.

RAMPVIS: Answering the challenges of building visualisation capabilities for large-scale emergency responses.

The effort for combating the COVID-19 pandemic around the world has resulted in a huge amount of data, e.g., from testing, contact tracing, modelling, treatment, vaccine trials, and more. In addition to numerous challenges in epidemiology, healthcare, biosciences, and social sciences, there has been an urgent need to develop and provide visualisation and visual analytics (VIS) capacities to support emergency responses under difficult operational conditions. In this paper, we report the experience of a group of VIS volunteers who have been working in a large research and development consortium and providing VIS support to various observational, analytical, model-developmental, and disseminative tasks. In particular, we describe our approaches to the challenges that we have encountered in requirements analysis, data acquisition, visual design, software design, system development, team organisation, and resource planning. By reflecting on our experience, we propose a set of recommendations as the first step towards a methodology for developing and providing rapid VIS capacities to support emergency responses.

Prevalence and factors associated with SARS-CoV-2 antibodies in a Spanish HIV cohort

Background: Within a prospective cohort of people with HIV (PWH) in Spain, we assessed the prevalence of SARS-CoV-2 antibodies (Ab), the proportion of asymptomatic COVID-19, and identified predictors of infection. Methods: We determined SARS-CoV-2 Ab in plasma samples collected from April 1st to September 30th, 2020, from enrollees in the Spanish HIV Research Network Cohort (CoRIS), a prospective national cohort of PWH, naive to ART at study entry, seen for the first time from January 1st, 2004. Samples were stored at-80°C in the Spanish HIV BioBank, and serology was performed using the Platelia SARS-CoV-2 Total Ab assays (BioRad, Hercules, CA, USA). Illness severity (NIH criteria) was assessed by medical records review and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes, non-AIDS related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, and N(t)RTI backbone. Results: During the study period, blood samples were collected and stored in the HIV BioBank from 1,076 consecutive PWH in CoRIS: 88.0% male at birth, median age 43 yr., 72.3% MSM, 97.7% on ART, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load. SARS-CoV-2 Ab were detected in 91 PWH, for a seroprevalence of 8.5% (95%CI: 6.9%-10.3%). A total of 41 PWH (45.0%) had asymptomatic infections;the disease was mild in 43 (47.3%), moderate in 4 (4.4%), severe in 3 (3.3%), and 0 critical. Seven PWH (7.7%) were hospitalized. COVID-19 was confirmed by RT-PCR in 22 (24.2%) PWH. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American (LA) Countries vs. Spain (adjusted odds ratio [aOR]: 2.34, 95%CI: 1.42-3.85;P=.001);arterial hypertension (aOR: 1.63, 95%CI: 1.00-2.67;P=.050);and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) vs tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR: 0.32, 95%CI: 0.12-0.84;P=.021). (Table). Conclusion: A large proportion of SARS-CoV-2 infections among PWH were asymptomatic. Birth in LA-countries and arterial hypertension were associated with increased risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggest that TDF/FTC may prevent SARS-CoV-2 infection among PWH. (Figure Presented).

Low Incidence and Mortality by SARS-CoV-2 Infection Among Healthcare Workers in a Health National Center in Mexico: Successful Establishment of an Occupational Medicine Program

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthcare workers (HCWs) constitute a population which is significantly affected by SARS-CoV-2 infection worldwide. In Mexico, the Instituto Nacional de Enfermedades Respiratorias (INER) is the principal national reference of respiratory diseases. Aim: To evaluate the efficiency of the INER-POL-TRAB-COVID19 program to mitigate the SARS-CoV-2 infection risk among the INER-healthcare workers (INER-HCW). Methods: Currently, the INER has 250 beds and 200 respiratory ventilators to support COVID-19 patients in critical condition. On March 1st, 2020, the INER-POL-TRAB-COVID19 program was launched to mitigate the SARS-CoV-2 infection risk among the INER-HCW. Findings: From March 1st to October 1st, 2020, 71.5% of INER-HCWs were tested for SARS-CoV-2 infection, and 77% of them were frontline workers. Among the tested INER-HCWs, 10.4% were positive for SARS-CoV-2 infection. Nonetheless, nosocomial infection represented only 3.8% of the cases and the mortality was null. Fifty-three of INER-HCWs positive to SARS-CoV-2 had a negative test 42-56 days post-diagnosis and were returned to service. Finally, although a change in the PPE implemented on May 11th, 2020, the incidence of SARS-CoV-2 infection was not affected. Conclusion: INER has a lower incidence of HCWs infected with SARS-CoV-2 as compared to the mean of the national report. The implementation of the INER-POL-TRAB-COVID19 program is efficient to decrease the risk of infection among the HCWs. Our findings suggest that the implementation of a similar program at a national level can be helpful to provide a safe environment to HCWs and to prevent the collapse of health institutions.

Risque de COVID-19 chez les patients atteints de rhumatismes inflammatoires chroniques et conséquences sur leur prise en charge

Introduction Depuis le début de l’épidémie de COVID-19, la prise en charge des patients atteints de rhumatismes inflammatoires chroniques a soulevé de nombreuses interrogations. À travers un questionnaire-patient, nous avons cherché à évaluer l’impact de l’épidémie sur les patients présentant un rhumatisme inflammatoire chronique, notamment concernant le maintien thérapeutique, et d’identifier des facteurs de risque de COVID-19 chez ces patients. Patients et méthodes Au début de la période de confinement en France, un questionnaire en ligne a été envoyé à l’ensemble des patients suivis pour une polyarthrite rhumatoïde (PR), une spondylarthrite (SpA) ou un rhumatisme psoriasique (RP) depuis 2019 dans un service de rhumatologie d’un centre hospitalier universitaire français. Le même questionnaire a été proposé aux patients atteints de SpA inscrits sur une plateforme d’e-santé. Ce questionnaire comprenait 39 questions concernant les caractéristiques sociodémographiques des patients, les caractéristiques de leur rhumatisme, leurs traitements et les événements survenus depuis le début de l’épidémie (contage, symptômes viraux, modification du traitement, report de consultation ou d’examens complémentaires). Les réponses ont été recueillies jusqu’au le 21 mai 2020. Les facteurs associés au risque de COVID-19 et à un arrêt de traitement à visée rhumatologique ont été évalués en régression logistique. Résultats Sur les 2081 questionnaires envoyés, nous avons obtenu 655 réponses provenant de 474 patients atteints de SpA, 129 de PR et 52 de RP. La moyenne d’âge était de 51 ans±13,4 ans avec une prédominance féminine (61,8 %). L’incidence de l’infection COVID-19 était de 6,9 % (IC95 % : 5,1–9,2 %), avec 12 cas confirmés par PCR et 33 fortes suspicions. Cinq patients ont nécessité une hospitalisation dont 1 en unité de soins intensifs et aucun décès n’a été constaté. Les facteurs de risque associés avec un risque d’infection étaient une notion de contage au SARS-CoV-2, un jeune âge, et l’absence d’intoxication tabagique. Plus de 30 % des patients rapportaient avoir suspendu ou arrêté au moins un traitement de leur rhumatisme inflammatoire durant la période de confinement, la plupart par peur d’une contamination (79,3 %). Parmi ceux-ci, 63,4 % ont rapporté une majoration de l’activité de leur maladie. Conclusion Notre étude ne rapporte pas de majoration de l’incidence ou de la sévérité de l’infection COVID 19 parmi les patients présentant un rhumatisme inflammatoire chronique, en comparaison à la population générale dans la même zone géographique. Elle met en revanche en avant la fréquence des interruptions thérapeutiques durant cette période et ses conséquences néfastes sur l’activité du rhumatisme. Ces résultats conjugués à ceux d’autres études aux résultats similaires plaident en faveur d’un maintien des traitements antirhumatismaux, y compris des AINS et des biothérapies.