Some drugs usually used in rheumatologic field and targeting the host and its immune response seem to have the potential to interfere with CoViD-19 infection and their potential benefit is being studied in patients (Fig. 1). The pathogenesis of CoViD-19 remains unclear, but modelling assays revealed a high degree of homology in the receptor binding domains between SARS-CoV2 and SARS-CoV. All coronaviruses express a surface glycoprotein termed a “spike” which bind to the host receptor for viral entry that has been identified as angiotensin-converting enzyme 2 receptors (ACE2r) [1], expressed by mature lung epithelial cells, enterocytes, kidney proximal tubular cells and endothelial cells [6]. After receptor binding, lysosomal proteases cleave the spike protein releasing the signal peptide that facilitates viral entry into the cell [7]. These mechanisms may be targeted and interrupted by therapies such as chloroquine, an antimalarial drug, and preliminary data demonstrate that it may have clinical benefit in the management of CoViD-19 infected patients as determined by improved imaging and shortening of the diseases course [8]. We should note that hydroxychloroquine, which shares the same mechanism of action as chloroquine but has a better safety profile and is frequently used particularly in connective tissue disease, has a more potent anti-viral effect than chloroquine in vitro. From the results of physiologically-based pharmacokinetic models, a loading dose of 800 mg orally followed by 400 mg daily for four days reaches three times the potency of chloroquine and is therefore a promising drug for both the prevention and the treatment of CoViD-19, with low risk of toxicity [9]. These findings have led to several clinical trials that are ongoing to study the efficacy of chloroquine or hydroxychloroquine in CoViD-19 patients. Hydroxychloroquine is thus being used in Italy for the treatment of CoViD-19 patients despite the absence of efficacy data in the clinical setting. In light of these data, the recommendation for rheumatic patients chronically taking antimalarial drugs is to not discontinue them, considering the antiviral efficacy and the immunomodulatory rather than immunosuppressive effect.
Fig. 1 Representation of possible mechanisms of action of anti-rheumatic drugs in coronavirus infection. AAK1 = AP2-associated protein kinase 1; SARS = severe acute respiratory syndrome.