• lupus erythematosus, systemic
• lupus nephritis
• hydroxychloroquine

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

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.