Last update and review: April 30, 2020.
As of the end of April 2020, we do not know yet if chronically administered hydroxychloroquine is protective against COVID-19 in systemic lupus erythematosus (SLE) patients. Therefore, remain prudent and mindful of side effects hydroxychloroquine and chloroquine. Wait until there is more data available.
Below, we publish an extended citation from a correspondence response by Sara Monti and Carlomaurizio Montecucco published on April 17, 2020 (1). The authors did a reasonably good summary of the current knowledge. Monti S, Montecucco C., 2020 (1):
Speculating on a preventive role of HCQ when the drug has been administered chronically is a currently unresolved issue of particular interest for rheumatologists. From our small published case series, three of eight symptomatic patients were taking HCQ, which did not seem to prevent the infection in these cases.3 It is still unknown whether the concomitant use of other immunosuppressive drugs might impair the supposed protective role of HCQ. Dr Joob and Wiwanitkit2 noted how, to date, there have been no reports of patients with SLE affected by COVID-19 in the literature and wondered whether this could be linked to the extensive use of HCQ in this population. However, this may only have been true for the time the authors wrote their correspondence and it might be only a matter of time to learn about SLE patients with COVID-19. Moreover, a recently published paper adds complexity to this scenario and warns on epigenetic dysregulation mechanisms that could lead to an increased risk and severity of SARS-CoV-2 infection in patients with SLE, regardless of the concomitant immunosuppressive medications. Patients with lupus would be characterised by hypomethylation and overexpression of ACE2, which encodes the receptor for SARS-CoV-2 spike glycoprotein, facilitating viral entry and enhancing viraemia. Moreover, oxidative stress induced by viral infections would exacerbate the DNA methylation defect, possibly perpetuating the mechanism. Similar modifications on interferon-regulated genes would then exacerbate the immune reaction to SARS-CoV-2 in these patients. The oxidative stress and DNA demethylation of ACE2 would be particularly activated during SLE flares, making the maintenance of disease remission even more critical in the course of COVID-19 pandemic.9 In our paper we had highlighted the need to ensure sustained remission in patients with rheumatic diseases, avoiding unnecessary withdrawal of treatments which would lead to increased disease activity, which is a well-known risk factor for infections. With this regard, several authors have been reporting on the shortage of HCQ supplies and the connected risk of relapses that patients with SLE and other rheumatic diseases are facing.10
These findings and the available evidence highlight how, even during these difficult and urgent times of the pandemic, rigorous, properly powered, well-conducted, randomised controlled trials on HCQ will be the only way to find reliable responses to the uncertainty regarding the optimal treatment of SARS-CoV-2 and the role of antirheumatic drugs in this infection. Large registry data are needed to clarify the incidence of COVID-19 in patients with SLE and other rheumatic diseases, the presence of potentially protective factors and treatments, and the outcome of these patients.
Reference list from the correspondance response by Sara Monti and Carlomaurizio Montecucco:
1. Heldwein FL, Calado A. Does hydroxychloroquine prevent the transmission of covid-19? Ann Rheum Dis 2020. doi:10.1136/annrheumdis-2020-217501. [Epub ahead of print: 15 Apr 2020].
2 Joob B, Wiwanitkit V. SLE, hydroxychloroquine and no SLE patients with covid-19: a comment. Ann Rheum Dis 2020. doi:10.1136/annrheumdis-2020-217506. [Epub ahead of print: 15 Apr 2020].
3 Monti S, Balduzzi S, Delvino P, et al. Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Ann Rheum Dis 2020:pii: annrheumdis-2020-217424
4 Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269–71.
5 Fantini J, Scala CD, Chahinian H, et al. Structural and molecular modeling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents 2020;105960.
6 Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of ZheJiang University 2020.
7 Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;105949:105949.
8 Perinel S, Launay M, Botelho-Nevers Élisabeth, et al. Towards optimization of hydroxychloroquine dosing in intensive care unit COVID-19 patients. Clin Infect Dis 2020:ciaa394.
9 Sawalha AH, Zhao M, Coit P, et al. Epigenetic dysregulation of ACE2 and interferonregulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clin Immunol 2020:108410.
10 Jakhar D, Kaur I. Potential of chloroquine and hydroxychloroquine to treat COVID-19 causes fears of shortages among people with systemic lupus erythematosus. Nat Med 2020. doi:10.1038/s41591-020-0853-0. [Epub ahead of print: 08 Apr 2020].
Selected references:
1. Monti S, Montecucco C. Can hydroxychloroquine protect patients with rheumatic diseases from COVID-19? Response to: ‘Does hydroxychloroquine prevent the transmission of COVID-19?’ by Heldwein and Calado and ‘SLE, hydroxychloroquine and no SLE patients with COVID-19: a comment’ by Joob and Wiwanitkit [published online ahead of print, 2020 Apr 23]. Ann Rheum Dis. 2020;annrheumdis-2020-217524. doi:10.1136/annrheumdis-2020-217524