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Since the global emergence of SARS-CoV-2 at the end of 2019, a special concern has raised regarding patients with rheumatic and inflammatory diseases, such as systemic lupus erythematosus (SLE).1 Indeed, many treated patients with SLE are immunocompromised and often suffer from chronic kidney or cardiovascular diseases.2 Recently, anti-interferon antibodies have been implicated in severe SARS-CoV-2 infection3 while it has been known for decades that patients with SLE may produce such autoantibodies.4 Although available data from short SLE series are reassuring,5 6 large-scale nationwide studies are still needed to assess the risk of developing severe SARS-CoV-2 infection in SLE.
We therefore used the French healthcare database system called ‘Programme de Médicalisation des Systèmes d’Information’—which contains hospitalisation data of all inpatients in France—to analyse the population with SLE that had at least one stay in a French hospital between March and 30 October 2020 (online supplemental material). On this population, we compared inpatients with SLE with or without SARS-CoV-2 infection (SLE/COVID-19+, SLE/COVID-19−). Among SLE/COVID-19+ inpatients, we distinguished patients with poor outcome after SARS-CoV-2 infection and patients with good outcome after COVID-19. We defined poor outcome as admission to intensive care unit (ICU) or death. We also compared the in-hospital mortality associated with SARS-CoV-2 infection in SLE and in the total population in France.
Based on the 10th International Classification of Diseases ‘M32’ and ‘L93’ diagnosis code, we identified 11 055 patients with SLE who had at least one stay in a French hospital between 1 March and 31 October 2020 (online supplemental material S1). Among them, 1411 (12.8%) also had a COVID-19 diagnosis code. Characteristics of SLE/COVID-19+ and SLE/COVID-19− patients are given in table 1. These 1411 SLE/COVID-19+ patients experienced 1721 inpatient hospital stays during the period of study.
Among these SLE/COVID-19+ inpatient hospital stays, 293 (17%) took place in ICU. The mean Simplified Acute Physiology Score II at admission was 35.4±16.8. In ICU, 78 (26.7%) and 71 (24.7%) SLE/COVID-19+ patients required invasive or non-invasive mechanical ventilation, respectively. Overall, 134 (9.5%) patients with SLE admitted for COVID-19 died. The in-hospital mortality rate was almost four times higher in SLE/COVID-19+ as compared with SLE/COVID-19− inpatients admitted during the same period (9.5% vs 2.4%, p<0.001). Interestingly, while the overall mortality rate was lower in SLE/COVID-19+ inpatients as compared with the total population admitted for SARS-CoV-2 infection in France during the same period (9.5% vs 15.7%, p<0.0001), the mortality rate at a younger age tended to be higher in patients with SLE. The difference failed however to reach statistical significance (online supplemental material S2).
Our study based on a comprehensive nationwide database confirms that inpatients with SLE are more likely to develop severe SARS-CoV-2 infection when they have comorbidities already identified as risk factors of severe infection in the general population, such as older age, male gender and hypertension.1 Poor outcome was associated with chronic kidney disease (CKD) status thus confirming that CKD increases the risk for severe infection in SLE and is a major predictor of mortality and morbidity in these patients.2 Since we only included hospitalised patients, excluding asymptomatic or mild forms of COVID-19, our results cannot be applied to all patients with lupus.
Given the importance of male sex as a poor prognosis factor of COVID-19, the lower mortality rate observed among inpatient population with SLE may be explained by an unbalanced sex ratio (F/M 8.5:1.5). On the other hand, the mortality of SLE/COVID-19+ patients seemed higher in the youngest patients as compared with the general population with SARS-CoV-2 infection. Because lupus activity and the need for immunosuppressive drugs decline with age, the higher mortality rate observed in younger patients, as compared with the one observed in general population, suggests that SLE disease may impact COVID-19 outcome.
Data availability statement
French hospital data for COVID19 are available at https://www.data.gouv.fr/fr/datasets/donnees-hospitalieres-relatives-a-lepidemie-de-covid-19/.
Handling editor Josef S Smolen
Contributors AM designed and conducted the analysis and wrote the manuscript. GA, DvG and TP were involved in the project development and edited the manuscript. KS and J-FT directed the project and wrote the manuscript.
Funding PhD fellowship support for AM was provided by Agence Nationale pour la recherche (no: ANR-19-CE17-0029).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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