1. Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which emerged for the first time in the city of Wuhan and rapidly spread through China to cause a disease known as coronavirus disease 19 (COVID-19) (http://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/). Because the outbreak of COVID-19 has rapidly spread worldwide, affecting millions of people, the World Health Organization (WHO) has declared SARS-CoV2 as a global pandemic (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020).
SARS-CoV2 is a new beta-coronavirus belonging to the same sub-group as Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and the Middle East Respiratory Syndrome-CoV (MERS-CoV) which caused SARS and MERS outbreak in 2002 and 2012, respectively (Chen, Liu and Guo, 2020). Several studies have identified a sequence homology of 79.5% between SARS-CoV2 and SARS-CoV (Zhou et al . 2020b; Wu et al . 2020). Therefore, SARS-CoV2 genome sequencing was rapidly performed, leading to the rapid availability of real-time PCR diagnostic test which is actually used to identify infected subjects allowing the epidemiologic tracking (Corman et al . 2020). SARS-CoV2 is a single-stranded RNA virus characterized by an envelope-anchored Spike glycoprotein which drives virus entry into target cells by binding membrane receptors of sensitive cells and leading to viral replication (Xu et al . 2020b).
Epidemiological data indicate that SARS-CoV2 infection progresses through human-to-human contact, which is predominantly realized via droplet transmission (Ong et al . 2020). As reported by WHO, the incubation period for SARS-CoV2 is 2-14 days, although a longer period may be at the basis of asymptomatic and subclinical infection (https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf ), whereas illness establishment occurs mainly in 10 days (Guan et al . 2020). Although the estimated case fatality rate (CFR) of COVID-19 floats from 5 to 15%, the number of deaths is very high. Indeed, as of May 4th 2020, the virus has infected over 3.4 million individuals in 215 countries, and 238198 people have lost their lives (https://www.who.int/emergencies/diseases/novel-coronavirus-2019).
Several reports have summarized the clinical and epidemiological features of patients affected by COVID-19. In the first published cohort of 41 laboratory-confirmed cases infected with SARS-CoV-2 (Huanget al . 2020), it was reported that infected patients had a median age of 49.0 years and 73% of them were men. The common symptoms were fever (98%), cough (76%), myalgia and/or fatigue (44%), and dyspnea occurred within 8 days from the establishment of the pathology in 55% of patients. Very few COVID-19 patients had gastrointestinal symptoms and prominent upper respiratory tract signs and symptoms, indicating that the target cells might be located in the upper and lower airways. All hospitalized patients showed abnormalities in chest computed tomography (CT) images, which were characterized by grinding glass-like and consolidation areas in 98% of the cases reporting bilateral lungs impairment at the basis of bilateral interstitial pneumonia. Because of complications, 32% of patients were admitted to an intensive care unit (ICU), among which 15% worsened in a short period of time. Most of them died of respiratory failure, but it is not excluded that death was due to organ failure, coagulation alteration with ensuing thrombosis and embolism as a consequence of blood clotting due to septic shock and/or cardiovascular complications (Huang et al . 2020). An exacerbation of SARS-CoV2-induced acute respiratory distress syndrome (ARDS) is characterized by thrombosis and ischemic events so that the check for coagulation parameters are daily needed.
It is well-known that in the early stages of ARDS, fluid from the pulmonary capillaries start to leak into the lungs, making oxygenation very difficult (https://www.lung.org/lung-health-diseases/lung-disease-lookup/ards/learn-about-ards). CT images from COVID-19 patients showed the presence of widespread ground-glass opacities in the lung, which represent the most common evidence of pulmonary edema (Hewitt et al . 2014) associated to bilateral diffuse alveolar damage due to high levels of pro-inflammatory concentrates typical of ARDS, as revealed by biopsy lung specimens from COVID-19 affected patients (Xu et al . 2020d).