The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET

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Abstract

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

Abstract

In this Perspective article, members of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases discuss clinical and organizational challenges in this community caused by the COVID-19 pandemic and what lessons might be learned for the future.

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Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry

Milena Gianfrancesco, Kimme L Hyrich, Sarah Al-Adely … (2020)

Objectives COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. Methods Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. Results A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. Conclusions We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

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Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies

Sara Monti, Silvia Balduzzi, Paolo Delvino … (2020)

Different viral agents are associated with an increased risk of more severe disease course and respiratory complications in immunocompromised patients.1–3 The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) responsible for a severe acute respiratory syndrome (SARS) represents a source of concern for the management of patients with inflammatory rheumatic diseases. Lombardy is the region in Northern Italy with the highest incidence of COVID-19 cases, with more than 33 000 confirmed patients and 1250 requiring admission to the intensive care unit within 1 month. Since the first reports of COVID-19 cases in Italy, we have circulated a survey with a 2-week follow-up contact to patients with chronic arthritis treated with biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) followed up at our biological outpatient clinic in Pavia, Lombardy. The survey investigated the patients’ health conditions, the presence of contacts with subjects known to be affected by COVID-19 and management of the DMARDs during the first few weeks of pandemic. All patients had provided their informed consent for the use of personal and clinical data for scientific purposes, and no patient refused to participate. During the first month, we have collected information on 320 patients (female 68%, mean age 55±14 years) treated with bDMARDs or tsDMARDs (57% with rheumatoid arthritis, 43% with spondyloarthritis, 52% treated with tumour necrosis factor inhibitors, 40% with other bDMARDs and 8% with tsDMARDs). As shown in table 1, four were confirmed cases of COVID-19 identified through rhinopharyngeal swabs. Another four patients reported symptoms which were highly suggestive of COVID-19. Five additional patients with reported certain contacts remained asymptomatic at the end of the 2-week observation period. Table 1 Clinical characteristics of the patients with confirmed or suspected COVID-19 Confirmed COVID-19 Clinical picture highly suggestive of COVID-19 Contact with a known COVID-19 patient Number of patients 4 4 5 Age (years) (mean±SD) 58±5 56±8 54±12 Female, n (%) 4 (100) 3 (75) 4 (80) Comorbidities, n (%) Hypertension 1 (25) 2 (50) 1 (20) Diabetes 0 0 0 Cardiovascular disease 0 0 1 (20) Other 4 (100) 4 (100) 3 (60) Smoking, n (%) Active 1 (25) 0 0 Previous 2 (50) 3 (75) 1 (20) Rheumatological diagnosis RA, n (%) 3 (75) 3 (75) 5 (100) SpA/PA,* n (%) 1 (25) 1* (25) 0 Rheumatological treatment, n (%) bDMARD Adalimumab 0 0 1 (20) Etanercept 2 (50) 2 (50) 0 Abatacept 1 (25) 1 (25) 0 Tocilizumab 0 0 1 (20) tsDMARD Tofacitinib 1 (25) 0 1 (20) Baricitinib 0 1 (25) 2 (40) Concomitant csDMARD Methotrexate 2 (50) 1 (25) 3 (60) Leflunomide 1 (25) 0 1 (20) Sulfasalazine 0 1 (25) 0 Concomitant hydroxychloroquine 1 (25) 2 (50) 2 (40) Low-dose glucocorticoids* 2 (50) 2 (50) 2 (40) Known contact with COVID-19 0 1 (25) 5 (100) Symptoms, n (%) Fever 4 (100) 1 (25) 0 Non-productive cough 3 (75) 2 (50) 0 Sputum production 1 (25) 0 0 Rhinorrhea 2 (50) 1 (25) 0 Sore throat 0 0 0 Fatigue 4 (100) 2 (50) 0 Myalgia 2 (50) 1 (25) 0 Arthralgia 1 (25) 1 (25) 0 Anosmia/dysgeusia 3 (75) 3 (75) 0 Dyspnoea at rest 1 (25) 0 0 Dyspnoea on exertion 2 (50) 1 (25) 0 Headache 2 (50) 0 0 Diarrhoea 1 (25) 0 0 Nausea/vomiting 0 0 0 Chest X-ray performed 4 (100) 0† 0 Chest X-ray pathological findings 0 0 0 Hospital admission 1 (25) 0 0 *Glucocorticoids≤5 mg/day prednisone equivalent. †Subject to home quarantine. bDMARD, biological disease-modifying antirheumatic drug; COVID-19, coronavirus disease 2019; csDMARD, conventional synthetic disease-modifying antirheumatic drug; PA, psoriatic arthritis; RA, rheumatoid arthritis; SpA, spondyloarthritis; tsDMARD, targeted synthetic disease-modifying antirheumatic drug. All patients with confirmed COVID-19 received at least one antibiotic course, and the hospitalised patient also received antiviral therapy and hydroxychloroquine. Overall, five patients were on previous stable treatment with hydroxychloroquine. All patients with symptoms of infection temporarily withdrew the bDMARD or tsDMARD at the time of symptom onset. To date, there have been no significant relapses of the rheumatic disease. None of the patients with a confirmed diagnosis of COVID-19 or with a highly suggestive clinical picture developed severe respiratory complications or died. Only one patient, aged 65, required admission to hospital and low-flow oxygen supplementation for a few days. Our findings do not allow any conclusions on the incidence rate of SARS-CoV-2 infection in patients with rheumatic diseases, nor on the overall outcome of immunocompromised patients affected by COVID-19. A high level of vigilance and strict follow-up should be maintained on these patients, including the exclusion of superimposed infections. However, our preliminary experience shows that patients with chronic arthritis treated with bDMARDs or tsDMARDs do not seem to be at increased risk of respiratory or life-threatening complications from SARS-CoV-2 compared with the general population. These findings are not surprising as the severe respiratory complications caused by coronaviruses are thought to be driven by the aberrant inflammatory and cytokine response perpetuated by the host immune system.4 During different coronavirus outbreaks, such as SARS and Middle East respiratory syndrome, there has been no increased mortality reported in patients undergoing immunosuppression for organ transplantation, cancer or autoimmune diseases.3 5 Accordingly, among 700 patients admitted for severe COVID-19 at our hospital (a referral centre for SARS-CoV-2 infection) during last month, none was receiving bDMARDs or tsDMARDs. Although continuous surveillance of patients with rheumatic diseases receiving immunosuppressive drugs is warranted, these data can support rheumatologists for the management and counselling of their patients, avoiding the unjustifiable preventive withdrawal of DMARDs, which could lead to an increased risk of relapses and morbidity from the chronic rheumatological condition.

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Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data

Matthieu Mahévas, Viet-Thi Tran, Mathilde Roumier … (2020)

Abstract Objective To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen. Design Comparative observational study using data collected from routine care. Setting Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020. Participants 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care. Interventions Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group). Main outcome measures The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting. Results In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. Conclusions Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.

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Author and article information

Contributors

Marta Mosca: ern.reconnet@ao-pisa.toscana.it

Journal

Journal ID (nlm-ta): Nat Rev Rheumatol

Journal ID (iso-abbrev): Nat Rev Rheumatol

Title: Nature Reviews. Rheumatology

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1759-4790

ISSN (Electronic): 1759-4804

Publication date (Electronic): 6 January 2021

Pages: 1-8

Affiliations

[1 ]GRID grid.144189.1, ISNI 0000 0004 1756 8209, Rheumatology Unit, , Azienda Ospedaliero Universitaria Pisana, ; Pisa, Italy

[2 ]Spanish Association for Antiphospholipid Syndrome (SAF España), Elche, Spain

[3 ]GRID grid.6363.0, ISNI 0000 0001 2218 4662, Department of Rheumatology and Clinical Immunology, , Charité University Medicine Berlin, ; Berlin, Germany

[4 ]GRID grid.411439.a, ISNI 0000 0001 2150 9058, Department of Internal Medicine, , Hospital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, French National Referral Center for SLE and APS, ; Paris, France

[5 ]GRID grid.413362.1, ISNI 0000 0000 9647 1835, Auto-immune Disease Unit, , Hospital de Curry Cabral, Centro Hospitalar de Lisboa Central, EPE, ; Lisbon, Portugal

[6 ]GRID grid.412220.7, ISNI 0000 0001 2177 138X, Service de rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre National de Référence des Maladies Systémiques et Auto-immunes Rares Grand-Est Sud-Ouest (RESO), ; Strasbourg, France

[7 ]GRID grid.29524.38, ISNI 0000 0004 0571 7705, Department of Allergology, Rheumatology and Clinical Immunology, , University Children’s Hospital, University Medical Centre Ljubljana, ; Ljubljana, Slovenia

[8 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Referral Center for Systemic Autoimmune Diseases, , Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, ; Milan, Italy

[9 ]GRID grid.5395.a, ISNI 0000 0004 1757 3729, University of Pisa, ; Pisa, Italy

[10 ]GRID grid.263145.7, ISNI 0000 0004 1762 600X, Institute of Management, Scuola Superiore Sant’Anna, ; Pisa, Italy

[11 ]GRID grid.419425.f, ISNI 0000 0004 1760 3027, Department of Rheumatology, , IRCCS Policlinico San Matteo Foundation, ; Pavia, Italy

[12 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Service de Médecine Interne, Hôpital Cochin, Centre de Référence Maladies systémiques Autoimmunes Rares d’Ile de France, Assistance Publique-Hôpitaux de Paris (AP-HP), , Université de Paris, ; Paris, France

[13 ]Lupus Europe, Brussels, Belgium

[14 ]GRID grid.5608.b, ISNI 0000 0004 1757 3470, Rheumatology Unit, Department of Medicine, , University of Padova, ; Padova, Italy

[15 ]GRID grid.7841.a, Medical Genetics Laboratory, Molecular Medicine Department, , San Camillo Forlanini Hospital, Sapienza University, ; Rome, Italy

[16 ]Department of Rheumatology, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

[17 ]GRID grid.411265.5, ISNI 0000 0001 2295 9747, Rheumatology Department, , Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon Academic Medical Centre, ; Lisbon, Portugal

[18 ]Flemish Association for Hereditary Connective Tissue Disorders, Koersel, Belgium

[19 ]Federation of European Scleroderma Associations (FESCA), Milan, Italy

[20 ]Deutsche Ehlers-Danlos Initiative e.V., Furth, Germany

[21 ]Liga Portuguesa Contra as Doenças Reumáticas, Lisbon, Portugal

[22 ]GRID grid.503367.4, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Systémiques et Auto-Immunes Rares du Nord-Ouest (CERAINO), , LIRIC, INSERM, Univ. Lille, CHU Lille, ; Lille, France

[23 ]GRID grid.48769.34, ISNI 0000 0004 0461 6320, Department of Rheumatology, , Cliniques Universitaires Saint-Luc, ; Brussels, Belgium

[24 ]GRID grid.411097.a, ISNI 0000 0000 8852 305X, Department of Dermatology, , Universitätsklinikum, ; Cologne, Germany

[25 ]Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

[26 ]GRID grid.410566.0, ISNI 0000 0004 0626 3303, Center for Medical Genetics, , Ghent University Hospital, ; Ghent, Belgium

[27 ]GRID grid.7429.8, ISNI 0000000121866389, Université Paris-Saclay, INSERM, CEA, Centre de recherche en Immunologie des infections virales et des maladies auto-immunes; AP-HP. Université Paris-Saclay, Hôpital Bicêtre, Rheumatology Department, Le Kremlin Bicêtre, ; Paris, France

[28 ]GRID grid.412220.7, ISNI 0000 0001 2177 138X, Clinical immunology department, Hôpitaux Universitaires de Strasbourg, Centre National de Référence des Maladies Systémiques et Auto-immunes Rares Grand-Est Sud-Ouest (RESO), ; Strasbourg, France

[29 ]Relapsing Polychondritis Awareness and Support, Worcester, UK

[30 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Division of Rheumatology and Scleroderma Unit, Department of Clinical and Experimental Medicine, AOU Careggi, , University of Florence, ; Florence, Italy

[31 ]GRID grid.419757.9, ISNI 0000 0004 0390 5331, Department of Rheumatology and Clinical Immunology, , Kerckhoff Klinik, Justus Liebig University of Giessen, ; Bad Nauheim, Germany

[32 ]Department of Rheumatology, Emergency County Teaching Hospital, Cluj-Napoca, Romania

[33 ]GRID grid.410566.0, ISNI 0000 0004 0626 3303, Department of Rheumatology, , Ghent University Hospital Department of Internal Medicine, ; Ghent, Belgium

[34 ]GRID grid.5606.5, ISNI 0000 0001 2151 3065, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, IRCCS Polyclinic Hospital San Martino, , University of Genoa, ; Genoa, Italy

[35 ]GRID grid.416651.1, ISNI 0000 0000 9120 6856, National Centre for Rare Diseases, Istituto Superiore di Sanità, ; Rome, Italy

[36 ]GRID grid.478758.1, Directorate-General for Health and Food Safety, European Commission, ; Brussels, Belgium

[37 ]GRID grid.7637.5, ISNI 0000000417571846, Rheumatology and Clinical Immunology Unit, , ASST-Spedali Civili and University of Brescia, ; Brescia, Italy

[38 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Internal Medicine and Immunology, , Erasmus MC, ; Rotterdam, Netherlands

[39 ]Liga Portuguesa Contra as Doenças Reumáticas, Núcleo Síndrome de Sjögren, Lisbon, Portugal

[40 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Rheumatology, , Leiden University Medical Center, ; Leiden, The Netherlands

[41 ]GRID grid.5395.a, ISNI 0000 0004 1757 3729, Rheumatology Unit, , University of Pisa, ; Pisa, Italy

Author information

Tobias Alexander http://orcid.org/0000-0003-1193-0097

Laurent Arnaud http://orcid.org/0000-0002-8077-8394

Fransiska Malfait http://orcid.org/0000-0002-5010-0304

Diana Marinello http://orcid.org/0000-0002-5537-6043

Article

Publisher ID: 565

DOI: 10.1038/s41584-020-00565-z

PMC ID: 7786339

PubMed ID: 33408338

SO-VID: ead15619-ec89-4066-b89b-4c6bee3c11fe

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET

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Most cited references 30

Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry

Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies

Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data

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