1. Introduction
Since the outbreak of COVID-19 epidemic, clinicians started a real
“gold rush” to find the best therapeutic option among those currently
available for infectious and inflammatory diseases
[1]. Waiting for a vaccine,
the study of COVID-19 clinical characteristics proved effective in
directing towards meaningful medical choices.
Three main stages represent COVID-19 infection clinical course. In the
first phase, the virus replicates within the host cells and patients may
experience symptoms as dry cough, fever, and general weakness and
malaise [2]. In the second
phase, the progression of the disease is characterised by the
development of a bilateral interstitial pneumonia and by morphological
changes in host’s lungs [3].
Respiratory symptoms, which could be stable in the first phase of
pneumonia, could worsen, due to both direct effects of the virus and
host’s immune response, leading to clinical instability and severe
hypoxemia [4]. Only in a
limited number of cases (third phase), patients experience a “cytokine
storm” and following hyper-inflammatory state, with local and systemic
consequences [5]. Among them,
at the lung level, arterial and venous vasculopathy, with thrombosis of
the small vessels and evolution towards serious and sometimes permanent
lung lesions. A progressive alteration of inflammatory and coagulation
parameters, such as C-reactive Protein (PCR), ferritin, pro-inflammatory
cytokines, consumption of clotting factors, and increased levels of the
fragments of fibrin degradation (D-dimer), have been observed
[6,
7].
In this complex scenario, therapeutic strategies have focused on viral
growth containment in the first and second phase of the disease, and on
inflammation and coagulation control, in the second and third phases
(Table 1 ) [8]. When
COVID-19 pandemic spread to Italy, the Italian Medicines Agency (AIFA)
approved the off-label use of the antiviral combinations
lopinavir/ritonavir and darunavir/cobicistat, the use of antimalarials
chloroquine and hydroxychloroquine (HCQ), the antibiotic azithromycin,
and the anticoagulant enoxaparin
[9]. Clinical experience
also suggested the use of tocilizumab, a humanized monoclonal antibody
against interleukin (IL)-6 receptor
[10].
However, the search for early and emergency effective treatments for
COVID-19 infection may have led to loss of sight of treatments safety.
From the beginning of COVID-19 pandemic, concerns about HCQ efficacy and
safety raised [11] and
subsequently AIFA suspended its use in SARS-CoV-2 patients out of
clinical trials on May 29th 2020
[12]. Moreover, based on
available evidence concerning the efficacy and safety of fixed
associations darunavir/cobicistat and lopinavir/ritonavir, AIFA also
suspended their use out of clinical trials on July
17th 2020
[13,
14].
Prevalence of adverse drug reactions (ADRs) in COVID-19 patients has not
yet been deeply evaluated, but results from observational studies
suggest that its frequency could be high in this population
[15]. The majority of ADRs
includes gastrointestinal and liver system disorders. Nevertheless,
potential harmful ADRs should be closely monitored, and
pharmacovigilance monitors’, toxicologists’ and clinical
pharmacologists’ support in COVID-19 Units should be carefully
considered in order to better manage COVID-19 therapies
[16]. In particular, good
quality information regarding drug-drug interactions (DDIs)-related ADRs
are still lacking.
In this context, the aim of the present case-series study is to describe
clinical and pharmacological characteristics of SARS-CoV-2 inpatients,
focusing on ADRs, particularly those related to DDIs.