Article Text

Download PDFPDF

Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine
  1. Alexis Mathian1,
  2. Matthieu Mahevas2,
  3. Julien Rohmer3,
  4. Mathilde Roumier3,
  5. Fleur Cohen-Aubart1,
  6. Blanca Amador-Borrero4,
  7. Audrey Barrelet5,
  8. Cecile Chauvet6,
  9. Thibaud Chazal1,
  10. Michel Delahousse7,
  11. Mathilde Devaux8,
  12. Romain Euvrard9,
  13. Jehane Fadlallah1,
  14. Nans Florens10,
  15. Julien Haroche1,
  16. Miguel Hié1,
  17. Laurent Juillard10,
  18. Raphael Lhote1,11,
  19. Thibault Maillet12,
  20. Gaelle Richard-Colmant13,
  21. Jean Baptiste Palluy9,
  22. Micheline Pha1,
  23. Laurent Perard14,
  24. Philippe Remy15,
  25. Etienne Rivière16,
  26. Damien Sène4,
  27. Pascal Sève13,
  28. Capucine Morélot-Panzini17,
  29. Jean-François Viallard16,
  30. Jean-Simon Virot18,
  31. Neila Benameur19,
  32. Noël Zahr20,
  33. Hans Yssel21,
  34. Bertrand Godeau2,
  35. Zahir Amoura1
  1. 1 Sorbonne Université, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France
  2. 2 Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Médecine Interne, Paris, France
  3. 3 Service de Médecine Interne, Hôpital Foch, Suresnes, France
  4. 4 Université de Paris (Paris-Diderot), Assistance Publique-Hôpitaux de Paris, Département de Médecine Interne et d'Immunologie Clinique Hôpital Lariboisière, Paris, France
  5. 5 Service de Maladies Infectieuses et Tropicales, Grand Hôpital de l'Est Francilien - Site de Marne-la-Vallée, Jossigny, France
  6. 6 Service de Néphrologie, Hôpital Saint-Joseph-Saint-Luc, Lyon, France
  7. 7 Service de Néphrologie, Hôpital Foch, Suresnes, France
  8. 8 Service de Médecine Interne, CHI Poissy Saint Germain, Poissy, France
  9. 9 Service de réanimation polyvalente, Centre Hospitalier Fleyriat, Bourg-en-Bresse, France
  10. 10 Université Lyon 1, Hospices Civils de Lyon, Hôpital Edouard Herriot, CarMeN - UMR INSERM U.1060, Service de néphrologie, hypertension, hémodialyse et explorations fonctionnelles rénales, Lyon, France
  11. 11 Sorbonne Université, UPMC, Institut Pierre Louis d’Epidémiologie et de Santé Public (IPLESP), UMRS 1136, Epidémiologie des Pathologies Allergique et Respiratoire (EPAR), Faculté de médecine de Saint Antoine, Paris, France
  12. 12 Service de Médecine Interne – Unité 11, Centre Hospitalier de Mâcon, Groupe Hospitalier Bourgogne Méridionale, Macon, France
  13. 13 Service de Médecine Interne, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
  14. 14 Service de Médecine interne, Hôpital Saint-Joseph-Saint-Luc, Lyon, France
  15. 15 Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Néphrologie, Paris, France
  16. 16 Internal Medicine Department, Hôpital Haut-Lévêque, Bordeaux University Hospital, Avenue de Magellan, Pessac, France
  17. 17 Sorbonne Université, INSERM, UMRS1158; AP-HP, Groupe Hospitalier Universitaire APHP Sorbonne Université, site Pitié-Salpêtrière, Service de Pneumologie et Réanimation Médicale (Département R3S), Paris, France
  18. 18 Service de service de Néphrologie/Dialyse, Centre Hospitalier de Mâcon, Groupe Hospitalier Bourgogne Méridionale, Macon, France
  19. 19 Service De La Pharmacie, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, Paris, France
  20. 20 Service De Pharmacologie, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, Paris, France
  21. 21 Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France
  1. Correspondence to Dr Alexis Mathian, Internal Medicine, University Hospital Pitié Salpêtrière, Paris 75013, France; alexis.mathian{at}aphp.fr

Statistics from Altmetric.com

The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) represents a source of concern for the management of patients with systemic lupus erythematosus (SLE). Indeed patients with SLE have an increased risk of severe infections due to intrinsic perturbations of their immune response, the use of immunosuppressive drugs, as well as the potential presence of organ damage associated with their disease. In this context, hydroxychloroquine (HCQ), a drug that is currently part of the long-term, standard-of-care treatment for SLE, has been reported to possess antiviral activity in vitro, and recent results from a preliminary clinical trial might support its use in curative or even prophylactic treatment for COVID-19.1–3

During the first days of the COVID-19 outbreak in France, we launched an observational study with the aim to follow the clinical course of COVID-19 in patients with SLE who received long-term treatment with HCQ. To be eligible, patients with SLE had to (1) fulfil the 1997 criteria of the SLE classifications of the American College of Rheumatology or those of the 2019 European League Against Rheumatism/American College of Rheumatology4 5; (2) be on long-term treatment with HCQ; and (3) have SARS-CoV-2 carriage in their nasopharyngeal swab, as confirmed by real-time reverse transcription PCR analysis.

Data were collected from 17 patients with SLE between 29 March and 6 April (tables 1 and 2). The initial symptoms of the first patient appeared on 5 March and those of the last patient on 26 March. The main comorbidities were obesity and chronic kidney disease, which were present in 10 (59%) and 8 (47%) patients, respectively. All patients except one had clinically quiescent SLE, defined as a clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score equal to 0.6 The duration of HCQ treatment prior to COVID-19 was relatively long, with a median (range) of 7.5 (0.5–29.8) years. Twelve (71%) patients were also treated with prednisone, at doses usually below 10 mg per day, and seven (41%) with an immunosuppressant. Except for a higher rate of dyspnoea, headache and diarrhoea, clinical signs and symptoms of COVID-19 were similar to those described previously.7 8

Table 1

Demographics and baseline characteristics of patients with SLE infected with SARS-CoV-2

Table 2

Clinical characteristics, laboratory results, treatment and outcome of patients with SLE infected with SARS-CoV-2

Viral pneumonia was diagnosed in 13 (76%) patients, with complications due to respiratory failure in 11 (65%) and acute respiratory distress syndrome in 5 (29%). Three patients suffered from acute renal failure, with two patients requiring haemodialysis. At admission, HCQ and prednisone were maintained at the same dose, whereas immunosuppressant drug intake was interrupted or decreased. HCQ blood concentrations were assessed in eight patients at admission or during hospitalisation. Its median (range) was 648 (254–2095) ng/mL. No additional antiviral treatments were started. Antibiotics were administered in nine (53%) cases even though no bacterial infections, except in one case, were documented. A total of 14 (82%) patients were admitted to hospital care, including 7 (41%) to an intensive care unit. Oxygen therapy was given to 11 (65%) patients, requiring nasal cannula in 5, high-flow nasal cannula in 1 and invasive mechanical ventilation in 5. One patient was treated with extracorporeal membrane oxygenation. As of 7 April, five (36%) patients have been discharged from the hospital, seven (50%) remained hospitalised and two (14%) died. Except for a single patient with active tenosynovitis at the onset of SARS-CoV-2 infection, none of the patients showed clinical signs of lupus during COVID-19.

This case series does not allow to draw conclusions on the incidence rate and severity of COVID-19 in SLE. However, it gives a first clinical picture of the course of this infection in patients with SLE treated with HCQ, and it furthermore paves the way for a larger observational study to identify the risk factors associated with the occurrence of a severe form of COVID-19 in patients with SLE. With a high prevalence of comorbidities such as chronic kidney disease and obesity, patients with SLE could suffer from severe forms of COVID-19.9 10 In patients with SLE with chronic renal disease, besides the risk of respiratory failure, the danger of acute renal failure should be considered as well.

At present, we are awaiting the results of the European Trial of Treatments for COVID-19 in Hospitalized Adults (DisCoVeRy, NCT04315948), which has the primary objective of evaluating the clinical efficacy and safety of different investigational therapeutics, including HCQ. Notwithstanding, our preliminary conclusion, based on the observation that most of the patients with SLE in this study received long-term treatment with HCQ, having blood concentrations of the drug within therapeutic range, is that HCQ does not seem to prevent COVID-19, at least its severe forms, in patients with SLE.

References

View Abstract

Footnotes

  • Handling editor Josef S Smolen

  • Contributors AM and ZA contributed to the conception and design of the study. AM, MM, JR, MR, FC-A, BA-B, AB, CC, TC, MiD, MaD, RE, JF, NF, JH, MH, LJ, RL, TM, GR-C, JBP, MP, LP, PR, ER, DS, PS, CM-P, J-FV, J-SV, NB, NZ and BG were involved in the acquisition of data. AM, HY and ZA contributed to the analysis and interpretation of data. All authors contributed to drafting and/or revising the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Patients were informed that data collected in medical records might be used for research study in accordance with privacy rules.

  • Ethics approval This observational study was based on data extracted from medical records, in strict compliance with the French reference methodology MR‐004, established by the French National Commission on Informatics and Liberty (CNIL), in accordance with the French law, including the GPRD. This study was approved by the Research Ethics Committee of Sorbonne University (CER-2020-12).

  • Provenance and peer review Not commissioned; internally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.