- Systemic lupus erythematosus is a probable risk factor to SARS-CoV-2 infection and severe COVID-19 presentation, independent of the immunosuppressive state from lupus therapy.
- In lupus patients, epigenetic dysregulation enhances viral entry into cells and induces pro-inflammatory changes resulting in a vicious cycle of cytokine response, and an increased possibility of cytokine storm.
- SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) receptors as an entry point into cells. ACE2 receptors are expressed by a methylation-sensitive gene on the X chromosome. Since lupus is a disease characterized by DNA demethylation, lupus patients show ACE2 hypomethylation, and thus probably overexpress ACE2 receptors (1.5 to 2-fold). ACE2 overexpression increases the likelihood of SARS-CoV-2 infection.
- Viral infections increase oxidative stress, which are known to induce lupus flares, and thus further increase DNA methylation defects.
- Maintaining lupus remission is essential to reduce DNA demethylation and oxidative stress. Therapies such as chloroquine (CQ) and hydroxychloroquine (HCQ) have been demonstrated to prevent flares, reduce disease activity and organ damage and improve survival in lupus patients. In the context of possible shortages of CQ and HCQ amid speculations of their role in treating COVID-19, clinicians should consider prioritizing lupus patients with available stocks of CQ and HCQ.
The data concerning SARS-CoV-2 infection in systemic lupus erythematosus in this article is not based on prospective or controlled data, but on fundamental data previously observed with the pathophysiological processes in both systemic lupus erythematosus and SARS-CoV-2.
- Sawalha AH, Zhao M, Coit P, Lu Q. (April 7, 2020). Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clin Immunol. https://doi.org/10.1016/j.clim.2020.108410.
- Jakhar D, Kaur I. (April 8, 2020). Potential of chloroquine and hydroxychloroquine to treat COVID-19 causes fears of shortages among people with systemic lupus erythematosus. Nat Med. https://doi.org/10.1038/s41591-020-0853-0.
- Peschken CA. (April 8, 2020). Possible Consequences of a Shortage of Hydroxychloroquine for Lupus Patients Amid the COVID-19 Pandemic. J Rheumatol. https://doi.org/10.3899/jrheum.200395.