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Background: Patients with autoimmune/infammatory rheumatic diseases (AIRD) were suspected to be an at-risk population of severe COVID-19. However, whether this higher risk is linked to the disease or to its treatment is difficult to determine. Objectives: To identify, among AIRD patients, factors associated with occurrence of moderate-to-severe COVID19 infection and to evaluate if having an AIRD was associated with an increased risk of severe form of COVID19 infection (defned by hospitalization in ICU or death), compared to general population. Methods: Data source: The 'Entrepôt des Données de Santé (EDS)' collect data from electronic health records of all patients hospitalized or followed in the AP-HP (39 hospitals in Paris area, France). The French RMD COVID19 cohort is a national multi-center cohort that included patients with confrmed AIRD and diagnosed with COVID-19. All AIRD patients diagnosed with COVID-19 before September 2020 from both cohorts were included.-We Identifed factors associated with severe COVID-19 was made in a combined analysis of the 2 cohorts.-Then, we compared COVID-19 infection severity in the EDS-COVID database in AIRD patients and controls, by a propensity score (PS)-matched case-control (1:4) study Results: Among 1213 patients (334 in EDS and 879 in RMD cohort), 195 (16.1%) experienced a severe COVID19. In multivariate analysis, greater age, history of interstitial lung disease, arterial hypertension, obesity, sarcoidosis, vas-culitis, auto-infammatory disease and treatment with corticosteroids or rituximab were associated with severe COVID-19 (Table 1). Among 35741 COVID-19 patients in EDS, 316 with AIRD were compared to 1264 PS-matched controls. Severe form occurred in 118 (37,3%) AIRD cases and 384 (30.4%) controls (Adjusted OR (aOR) for severe form= 1.43 [1.1;1.9], p=0,01). In analysis restricted to rheumatoid arthritis (RA) and spondylarthritis (SpA), no increased risk of severe form (aOR=1.11 [0.68;1.81]) form or death (aOR=1.00 [0.55;1.81]) was observed. Conclusion: In this multicenter study we confirmed that AIRD patients treated with rituximab or corticosteroids were at increased risk of severe COVID-19, as were those with vasculitis, auto-inflammatory disease, and sarcoidosis. Also, when compared to controls from the same cohort of hospitalized patients, AIRD patients had, overall, an increased risk of severe COVID-19, increased risk not observed in an analysis restricted to patients with RA or SpA.
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Background: The efficacy of COVID-19 convalescent plasma (CCP) as passive immunotherapy in hospitalized COVID-19 patients remains uncertain. The transfusion of a large volume of high titre CCP in recently hospitalized patients may be beneficial. Aims: To evaluate the ability CCP transfusion to improve early outcome in patients with moderate to severe COVID-19 pneumonia. Methods: The CORIPLASM study was a multicentric, open-label, Bayesian randomized, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalized with COVID-19 in 14 French centers, requiring at least 3 L/min of oxygen but without mechanic ventilation assistance and a WHO Clinical progression scale [CPS, 1 to 10] of 4 or 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomization list stratified on center, to receive usual care plus 4 units of CCP (2 units/day over 2 days) (CCP group) or usual care alone (usual care group) on day 1 and 2 post-enrollment. Primary outcomes were the proportion of patients withWHO CPS greater than 5 on the 10-point scale on day 4 and survival without ventilation or additional immunomodulatory treatment by day 14. Results: One hundred and twenty patients were recruited from April 16th 2020 and April 21th 2021 and randomly assigned to the CCP group (n = 60) and to the usual care group (n = 60) and followed up for 28 days. Immunosuppressed patients comprised 43% (26/60) and 50% (30/60) of patients in the CCP and usual care groups, respectively. Median time from symptoms onset to randomization (days) was 7.0 [interquartile range (IQR): 5.0-9.0] in the CCP group and 7.0 [IQR: 4.0- 8.5] in the usual care group. Thirteen (22%) patients in the CCP group had a WHO CPS greater than 5 at day 4 versus 8 (13%) in the usual care group (adjusted odds ratio (OR): 1.88 [95% CI: 0.71 to 5.24]. By day 14, 19 (31.6%) patients in the CCP and 20 (33.3%) patients in the usual care group had needed ventilation, additional immunomodulatory treatment or had died (adjusted HR: 1.04 [95% CI: 0.55 to 1.97]). The cumulative incidence of death was 3 (5%) in the CCP group and 8 (13%) in the usual care group at day 14 (adjusted HR: 0.40 [95% CI: 0.10 to 1.53]), and 7 (12%) in the CCP group and 12 (20%) in the usual care group at day 28 (adjusted HR: 0.51 [95% CI: 0.20 to 1.32]). Frequency of severe adverse events did not differ significantly between both treatment arms. Subgroup analysis revealed that mortality at day 28 was mostly observed in the immunosuppressed patients (15/56 vs. 4/64) and that CCP was associated with less mortality in these patients (4/26 in the CCP group vs. 11/30 in the usual care group)(HR: 0.36 [95% CI: 0.14-0.97]). Summary/Conclusions: CCP treatment did not improve early outcome in patients with moderate-to-severe COVID-19 pneumonia. CCP-associated early respiratory worsening as well as CCP-associated reduced D14 and D28 mortality were observed, while not reaching statistical significance. CCP treatment was associated with reduced D28 mortality in immunosuppressed patients.
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La vaccination contre la COVID-19 représente le meilleur moyen pour prévenir les formes sévères de l'infection par le SARS-Cov2. Une seule étude a été publiée récemment sur les vaccins contre COVID-19 chez 175 patients suivis pour les maladies auto-inflammatoires (MAI), principalement des cryopyrinopathies [1]. De nombreux patients avec MAI suivis dans le centre national français de référence se sont posé des questions sur la vaccination et exprimaient parfois certaines des réticences. Nous avons donc mené une enquête auprès des patients adultes avec MAI afin d'évaluer la tolérance des vaccins anti-COVID-19, le risque de poussées de leur maladie après la vaccination, et leurs effets indésirables à court terme tels que le risque thromboembolique. Un sondage en ligne anonyme a été envoyée entre le 7 et le 30 juin 2021 à 445 patients adultes suivis dans le centre de référence national des maladies auto-inflammatoires et inclus dans la cohorte JIR (une cohorte européenne sur les maladies autoinflammatoires). Il évaluait les effets indésirables survenant après la vaccination anti-COVID-19. Il était demandé aux patients s'ils avaient reçu une vaccination anti- COVID-19, le type de vaccin le nombre d'injections et les effets indésirables. Les effets indésirables graves ont été définis par la nécessité d'une hospitalisation. Deux cent vingt-cinq patients (50 %) ont répondu. Parmi les 190 patients ayant reçu 2 deux doses du vaccins anti-COVID-19, les pathologies concernées étaient respectivement : la fièvre méditerranéenne familiale (FMF) (n = 128, 67,4 %) ;les MAI inclassée (n = 20), le syndrome périodique associé aux récepteurs TNF- α (n = 13), les cryopyrinopathies et la maladie de Still (n = 9 chacun), le déficit en mévalonate kinase (n = 7) et l'haploinsuffisance de A20 (n = 4). Onze patients avaient une amylose AA (5,7 %). La colchicine était le traitement prédominant (n = 138, 72,6 %) ;37 (19,5 %) patients étaient sous biothérapie, principalement sous inhibiteurs de l'interleukine-1 (n = 33) et 15 patients ne prenaient aucun traitement. Quarante-six patients avaient déjà contracté le SARS-Cov2. Sur les 190 patients (84,4 %) vaccinés, Pfizer/BioNTech (n = 157, 82,6 %) et l'Astra Zeneca (n = 22, 11,5 %) étaient les vaccins les plus courants ;11 patients (5,8 %) avaient reçu Moderna. Quatre-vingt-huit patients (46 %) rapportaient des réactions mineures après la première injection et 70 patients (54 %) après la seconde injection. Parmi les 157 patients ayant reçu Pfizer/BioNTech, la douleur au niveau du site d'injection était souvent rapportée (25,5 %). Concernant l'Astra Zeneca, les patients rapportaient principalement de la fièvre (n = 13, 59 %) et des myalgies (n = 11, 50 %). Concernant le Moderna, 4 patients avaient rapporté de la fièvre et des myalgies (36 %). Aucun effet indésirable grave nécessitant une hospitalisation n'avait été signalé. Douze patients atteints de FMF (9,3 %) avaient rapporté une poussée après la première injection. Les effets indésirables de la vaccination COVID-19 chez les patients avec MAI sont similaires à ceux rapportés dans la population générale [2]. Chez les patients FMF sous colchicine, le vaccin anti-COVID-19 est être fortement recommandé pour les patients présentant des facteurs de risque de forme sévère de COVID-19. La vaccination contre le COVID-19 ne semble pas déclencher de poussée de MAI. Ces données permettront de rassurer les patients atteints du MAI qui hésitent encore à se faire vacciner conter la COVID-19 de peur d'effets indésirables. (French) [ FROM AUTHOR] Copyright of Revue de Médecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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Background: Various observations have suggested that the course of the COVID-19 infection may be less favorable in patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving rituximab (RTX). Objectives: To investigate whether treatment with RTX is associated with severe infection and death. Methods: We performed an observational, multicenter, French national cohort study querying the French RMD COVID-19 cohort, including highly suspected/ confirmed iRMD-COVID-19 patients. The primary endpoint was to assess the severity rate of COVID-19. Severe disease was defined by hospitalization in intensive care unit or death. The secondary objectives were to analyze death rate and length of hospital stay. Two control groups were considered for comparison with RTX treated patients: a first group including all non-RTX treated iRMD patients and a second consisting on RTX untreated iRMD patients with diseases for which RTX is a recognized therapeutic option. Adjusting on potential confounding factors was performed by using inverse probability of treatment weighting (IPTW) propensity score method. Results: We collected a total of 1090 records. Patients were mainly females (67.3%, 734/1090) with a mean age of 55.2±16.4 years, and 51.1% (557/1090) were over the age of 55. Almost 70% of the population had at least one comorbidity (756/1090). A total of 63 patients were treated with RTX, mainly for rheumatoid arthritis (RA) (31/63, 49.2%). RTX treated patients were more likely to be males, with older age, higher prevalence of comorbidities and corticosteroid use. The control population consisted on 1027 non-RTX treated iRMD patients, and 495 RTX untreated iRMD patients with diseases for which RTX is a recognized therapeutic option. Of the 1,090 patients, 137 developed severe disease (12.6%). After adjusting on potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure and the underlying disease), severe disease was confirmed to be observed more frequently in patients receiving RTX compared to all RTX untreated iRMD patients (effect size, ES 3.26, 95% confidence interval, CI 1.66 to 6.40, p<0.001) and the subgroup of untreated RTX patients with diseases eligible for RTX therapy (ES 2.62, 95% CI 1.34 to 5.09, p=0.005). Patients who developed a severe disease had a more recent rituximab infusion compared to patients with mild or moderate disease. Indeed, the time between the last infusion of rituximab and the first symptoms of COVID-19 was significantly shorter in patients who developed a severe form of COVID-19 (Figure 1). Eighty-nine patients in our cohort died, resulting in an overall death rate of 8.2%. Death rate was numerically higher in RTX treated patients (13/63, 20.6%) compared to all RTX untreated iRMDs patients (76/1027, 7.4%) and the subgroup of untreated RTX patients with diseases eligible for RTX therapy (49/495, 9.9%). After considering the previously described confounding factors, the risk of death was not significantly increased in patients treated with RTX compared to all RTX untreated iRMDs patients (ES 1.32, 95% CI 0.55 to 3.19, p=0.53) (Table 2) and the subgroup of untreated RTX patients with diseases eligible for RTX therapy (ES 1.48, 95% CI 0.68 to 3.20, p=0.32). In line with a more severe COVID-19 disease, the length of hospital stay was markedly longer in patients treated with RTX compared to both untreated RTX patient groups. Conclusion: RTX therapy is associated with a more severe COVID-19 infection. RTX will have to be applied with particular caution in patients with iRMDs.
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La nouvelle pandémie mondiale (COVID19) causée par le coronavirus 2 du syndrome respiratoire aigu sévère (SRAS-CoV-2) est responsable de nombreux décès dans le monde entier au cours des derniers mois. Au cours des formes graves, il a été noté une réponse inflammatoire exagérée connue sous le nom de "orage cytokinique". Ceci a soulevé la question de la sensibilité et de la gravité de l'infection par le SRAS-CoV2 chez les patients présentant une hyperactivation génétique de l'immunité innée tels que la fièvre méditerranéenne familiale (FMF). En outre, les patients avec FMF prennent de la colchicine au long cours, médicament qui a été testé chez des patients infectés par le SRAS-CoV2 avec des résultats contradictoires [1]. Étude menée sur l'infection par le SRAS-CoV2 chez les patients atteints de FMF suivis dans 2 sites du centre de référence national des maladies autoinflammatoires en région parisienne et inclus dans la JIR cohorte, une base de données européenne multicentrique. Les patients adultes et pédiatriques inclus répondaient aux critères internationaux de FMF et avaient un diagnostic génétique confirmé. Les patients identifiés (n = 627) ont été invités à répondre à un bref questionnaire soit en consultation, soit par téléphone, soit par courrier électronique sur une possible infection par le SARS-CoV2 pendant la période de mars à juin 2020 ;342 patients ont répondu à l'enquête. Le diagnostic était retenu si le patient présentait des symptômes cliniques avec PCR ou sérologie positive ou scanner thoracique typique. Au total, 27 patients FMF (7,8 % des répondants ;sexe ratio 1/1) ont contracté le virus. Tous les 27 patients FMF-COVID+ sauf un prenaient de la colchicine quotidiennement depuis une période médiane de 23 ans, la dose moyenne de colchicine était de 1 mg/jour. Quatre recevaient en plus un inhibiteur de l'IL-1. Parmi les 27 patients FMF-COVID+, sept symptomatiques ont été hospitalisés (25 %) et six ont eu besoin d'oxygène ;trois (11 %) ont développé un syndrome de détresse respiratoire aiguë nécessitant des soins intensifs pour une ventilation mécanique et une hémodialyse. Deux patients sont décédés (7 %) mais présentaient respectivement 3 et 4 comorbidités pour une infection grave par le SRAS-CoV2 ;le troisième patient, âgé de 40 ans, souffrait d'hypertension et d'obésité. Les patients âgés de plus de 65 ans représentaient 17 % de l'ensemble de la cohorte FMF-COVID + ;75 % ont été hospitalisés et ont eu besoin d'oxygène ;l'un d'eux est décédé. Trois patients FMF-COVID + avaient une amylose AA : 2 ont été hospitalisés et un est décédé. Aucun traitement anti-viral supplémentaire n'a été administré. Les 5 survivants après hospitalisation sont rentrés chez eux. Aucun d'entre eux n'a présenté de signes cliniques de crise de FMF lors de l'infection par le SRAS-CoV2. Le profil des patients FMF atteints d'une forme grave ou potentiellement mortelle par le SRAS-CoV2 était le même que celui de la population générale. Ainsi, seuls les patients FMF présentant des facteurs de risque connus (tels que âge avancé, maladie rénale chronique, hypertension, maladie vasculaire, obésité et dysfonctionnement pulmonaire) ont développé une infection grave par le SARS-CoV2 [2]. Cette étude n'est pas en faveur d'un surrisque en soi de développer une infection sévère à SRAS-CoV2 en présence d'une maladie autoinflammatoire monogénique touchant un inflammasome. Aucune conclusion formelle ne peut être tirée sur l'effet préventif de la colchicinothérapie au long cours, bien que ce travail rétrospectif porte sur une large cohorte de patients traités par colchicine depuis plusieurs années. Il est difficile de conclure à l'efficacité du traitement par inhibiteur d'IL1 vis-à-vis l'infection par le SRAS-CoV-2 chez les patients FMF, mais 50 % des patients traités au long cours sont décédés mais avaient plusieurs comorbidités ;et des publications récentes semblent plaider en faveur de l'e ficacité de l'anakinra dans l'infection grave par le SRAS-CoV-2 [3]. La FMF ne semble pas constituer un facteur de risque de développer une forme sévère d'infection par SARS-CoV2 chez les patients traités au long cours par de la colchicine quotidienne, par rapport à la population générale. (French) [ABSTRACT FROM AUTHOR] Copyright of Revue de Médecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
OBJECTIVES: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) a pandemic. In absence of official recommendations, implementing daily multidisciplinary team (MDT) COVID-19 meetings was urgently needed. Our aim was to describe our initial institutional standard operating procedures for implementing these meetings, and their impact on daily practice. METHODS: All consecutive patients who were hospitalized in our institution due to COVID 19, from March 31 to April 15, 2020, were included. Criteria to be presented at MDT meetings were defined as a proven COVID-19 by PCR or strongly suspected on CT scan, requiring hospitalization and treatment not included in the standard of care. Three investigators identified the patients who met the predefined criteria and compared the treatment and outcomes of patients with predefined criteria that were presented during MDT meeting with those not presented during MDT meeting. COVID-19 MDT meeting implementation and adhesion were also assessed by a hospital medical staff survey. RESULTS: In all, 318 patients with confirmed or suspected COVID-19 were examined in our hospital. Of these, 230 (87%) were hospitalized in a COVID-19 unit, 91 (40%) of whom met predefined MDT meeting criteria. Fifty (55%) patients were presented at a MDT meeting versus 41 (45%) were not. Complementary exploration and inclusion in the CorImmuno cohort were higher in MDT meeting group (respectively 35 vs. 15%, P=0.03 and 80 versus 49%, P=0.0007). Prescription of hydrocortisone hemisuccinate was higher in group of patients not presented during MDT meeting (24 vs. 51%, P=0.007). Almost half of the patients fulfilling the inclusion criteria were not presented at MDT meeting, which can be partly explained by technical software issues. CONCLUSIONS: Multidisciplinary COVID-19 meetings helped implementing a single standard of care, avoided using treatments that were untested or currently being tested, and facilitated the inclusion of patients in prospective cohorts and therapeutic trials.