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No evidence so far on the protective effect of hydroxychloroquine to prevent COVID-19: comment by Joob and Wiwanitkit
  1. Vasco C. Romão1,2,
  2. Ana Rita Cruz-Machado1,2,
  3. João Eurico Fonseca1,2
  1. 1 Rheumatology Department, Hospital de Santa Maria, CHULN, Lisbon Academic Medical Centre, Lisbon, Portugal
  2. 2 Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  1. Correspondence to Prof. João Eurico Fonseca, Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes. Av Prof Egas Moniz, 1649-028, Lisbon, Portugal; jecfonseca{at}

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We read with interest the comment by Joob and Wiwanitkit1 on the letter published by Monti et al in the Annals of the Rheumatic Diseases (ARD).2 In it, the authors state that there are no reported cases of patients with systemic lupus erythematosus (SLE) with COVID-19 and suggest that this may be due to a protective effect of hydroxychloroquine, a mainstay treatment taken by most patients with SLE. A similar suggestion had already been made earlier this month in the ARD by colleagues from Italy,3 the first hardly-hit western country, and was reinforced by yet another recently published letter.4

As is now widely known, this old antimalarial drug, which has been part of the daily therapeutic armamentarium of rheumatologists for decades, has reached the global spotlight after demonstration of antiviral efficacy in vitro5 and some suggestions of clinical efficacy in studies with methodological limitations and fast peer-review processes.6 The scientific discussion on the potential validity of these findings—which were to be confirmed—was seized by some politicians who quickly transformed it into a matter of belief and conviction. Moreover, an additional problem was created in several countries, where a general run to antimalarials led to nationwide drug shortage and prevented patients with rheumatic diseases from accessing these critical drugs to control their disease.

The yearning for an effective treatment for COVID-19 should not deter the scientific community from critically evaluating available evidence. Rather, it should make it raise the bar even higher to avoid that possible spurious findings are used in the wrong way.

In this regard, we would like to dispute both the statement and the suggestion by Joob and Wiwanitkit in their comment.1 Indeed, the authors comment on the letter by Monti et al, who studied a cohort of 320 patients with rheumatoid arthritis (RA) or spondyloarthritis, but did not have a single patient with SLE.2 Still, out of the eight patients who developed a clinical picture compatible with COVID-19, three were already on hydroxychloroquine, making it confusing to suggest a protective effect of this drug. Recently, the COVID-19 Global Rheumatology Alliance launched a worldwide register for patients with rheumatic diseases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.7 In the initial report that was just published, 19 out of 110 patients had SLE, although no treatment/outcome details were provided specifically for these patients.8

Additionally, we report two cases of patients with SLE under long-term treatment with hydroxychloroquine, who developed COVID-19 (table 1). Both were young patients, with controlled disease activity prior to the infection. Both had confirmed close contacts with subjects later diagnosed with COVID-19, developed mild disease and fully recovered. While these two cases do not provide any definite answer to the question of whether antimalarials can prevent COVID-19 or severe disease, they show that, indeed, patients with SLE can develop disease, even if on stable hydroxychloroquine therapy. The mild disease course should not be attributed to the concomitant antimalarial. Rather, it is likely related to other factors known to be associated with better outcomes, such as female sex and younger age.

Table 1

Clinical features of two patients with SLE who developed COVID-19

In these agitated, confusing times, caution is warranted in interpreting the vast amount of information emerging on COVID-19. Until robust evidence is available, we should stick to what we know by now: antimalarials are crucial drugs for patients with SLE, RA and other rheumatic diseases, who also seem to be susceptible to infection by SARS-CoV-2. Whether they are effective drugs for the prevention or treatment of COVID-19 is yet an open avenue. One we should not rush into without decisive, firm steps.



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  • Contributors VCR, ARC-M, JEF: study conception and design, data acquisition, data analysis, manuscript preparation and critical revision. All authors read and approved the final version of 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, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Obtained.

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

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