INTRODUCTION
Since December 2019, cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to a novel disease called COVID-19 were initially identified in China. SARS-CoV-2 infection causes respiratory symptoms that range from mild forms of presentation to more serious ones that can risk patients’ lives, causing pneumonia, and damage to other organs, particularly the immune and blood system (Wang et al., 2019; Huang et al., 2020; Chen et al., 2020). This disease has rapidly expanded to multiple countries leading to a pandemic situation in March 2020 now affecting 5.595.091 individuals worldwide, with a global mortality of 350.547 deaths on May 27th. Today, the situation is dramatic in some European countries, such as Spain with 236.259 cases and 27.117 deaths, being the 2nd country in the world with higher COVID-19 mortality per capita, following Belgium (Dong E and Du H, 2020). This official mortality numbers only reflect the casualties occurring in the hospitals, not in nursing homes or at home, and considering the low availability of accurate COVID-19 diagnostic tests, the current situation in Spain could unfortunately be worse. Furthermore, some patients are asymptomatic (Mizumoto and Kagaya, 2020; Nishiura et al., 2020) and the current prevalence reflects a possible underdiagnosis of the infection that has facilitated the disease expansion. This, together with the massive social and political activities that were promoted in Spain in early March in spite of the well-known previous recommendations of the WHO could influence this rapid progression.
Severe cases of the disease represent about 15% of COVID-19 patients (Wu and Mc Googan, 2020) and require their hospitalization. Given the progressive spread of the pandemic in relation to the available health resources, it is essential to find new equally effective treatments, especially when evidence indicates that a rapid shortage of some of the existing treatments’ stock may occur. Therefore, there is an urgent need to find novel treatments in the early stages of COVID-19 to prevent the progression to severe forms of the disease. Evidence suggests that the hyperactivation of the immune response is of paramount relevance in COVID-19 progression. The accumulated knowledge about the pathophysiology of this disease reveals a crucial involvement of different molecules of the main inflammatory pathways, including interleukins 1, 6 and 8 (IL-1, IL-6, IL-8) and tumour necrosis factor alpha (TNFα). Currently, drugs inhibiting some of these pathways are used in the routine management of COVID-19, although results from clinical trials are still required to corroborate their effectiveness (Zhang et al., 2020). Clear examples are anti-IL-6 compounds for patients with severe forms of COVID-19 (Zhang et al., 2020; Zhou et al., 2020; Fu and Xu , 2020) and hydroxychloroquine, widely used and highly questioned that has been now withdrawn from the clinical trials due to the serious adverse effects (Mehra et al., 2020; Adhanom Ghebreyesus, 2020).
Immunomodulated inflammatory diseases (IMIDs) are a group of unrelated and highly diverse conditions, such as rheumatoid arthritis and psoriasis, that share a common pathogenesis pathway, i.e., an immune dysregulation leading to an imbalance in inflammatory cytokines. Treatments to relieve IMIDs symptoms share similar mechanisms of action and are namely disease modifying antirheumatic drugs (DMARDs), subdivided into two main subgroups: synthetic and biological. Biological DMARDs (bDMARDs) are monoclonal antibodies that have a much higher affinity and selectivity for the targeted protein than synthetic DMARDs (sDMARDs). Patients with an autoimmune disease might be at higher risk of developing severe infections, as these medications are immunosuppressants (Memoli et al., 2014). In that context, the Rheumatology, Dermatology and Gastroenterology services of Hospital del Mar began to follow-up more closely on their patients and, surprisingly, they reported less COVID-19 symptoms than expected. Considering the role of the immune system in COVID-19 progression and that these immunomodulatory treatments are not associated with worse COVID-19 outcomes (Haberman et al., 2020) we hypothesize that specific compounds used in IMIDs treatment could provide therapeutic benefits in early stages of COVID-19.