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.