There is compelling evidence suggesting that SARS-CoV-2 infection may be asymptomatic, pauci-symptomatic, or symptomatic [
21]. Although COVID-19 is generally a mild disease in children and infants, in some cases it may manifest in younger age groups as a multisystem inflammatory syndrome with Kawasaki’s disease-like features (e.g., fever, mucocutaneous manifestations, cervical lymphadenopathy, conjunctival injection, cardiac involvement) or even multiorgan failure [
22]. In adulthood, the clinical spectrum of symptomatic SARS-CoV-2 infection is extremely heterogeneous, ranging from mild to severe and potentially life-threatening manifestations [
21]. The most common initial symptoms, including fever, dry cough, myalgia, or fatigue, are generally mild and non-specific [
21,
23]. Less commonly, COVID-19 clinical onset is characterized by nausea, vomiting, diarrhea, abdominal pain, and anosmia with or without dysgeusia [
24,
25]. A delayed progression to dyspnea with respiratory failure requiring hospital admission has been reported to occur in more than half of cases [
21,
26]. According to different reports, hypertension, cardiovascular diseases, and diabetes mellitus are the three most prevalent underlying co-morbidities among COVID-19 patients undergoing hospitalization [
27]. Upon hospitalization, intensive care unit (ICU) admission may be required in about 20% of cases due to either acute respiratory distress syndrome (ARDS) or other severe complications, including DIC and other thrombotic disorders [
23]. Although early reports have described ARDS and multi-organ failure as the main in-hospital complications of COVID-19, more recent studies have shown that venous thromboembolism and arterial thrombosis have a high incidence rate and a detrimental impact on prognosis of hospitalized COVID-19 patients [
7,
28]. In addition, evidence of myocardial injury, likely due to a combination of a direct virus-mediated and an indirect immune-mediated injury of cardiomyocytes, has been frequently found in patients with COVID-19 [
29,
30]. In a Chinese cohort of 416 hospitalized patients with COVID-19, individuals with myocardial injury were more likely to necessitate ventilation and die because of COVID-19 complications [
31]. Also, in a Chinese case series of 72,314 COVID-19 patients, the overall case fatality rate was 2.3%, but it reached 6%, 7.3%, and 10.5% in patients with hypertension, diabetes, or underlying cardiovascular disease [
32]. Moreover, mortality exceeded 50% in a retrospective case series of 187 COVID-19 patients with myocardial injury [
33].
Clinical and laboratory features of hospitalized COVID-19 patients are predictive of COVID-19 progression towards its most severe clinical manifestations and fatal outcome [
34‐
38]. These features include: older age, underlying co-morbidities, higher Sequential Organ Failure Assessment (SOFA) scores (indicative of organ dysfunction), abnormal hemostasis parameters (i.e., increased levels of D-dimer and fibrin degradation products, and decreased platelet counts) and increased biomarkers of cardiac injury and dysfunction (i.e., N-terminal pro-brain natriuretic peptide and troponin) [
34‐
38]. Thus, in a retrospective case series of 187 COVID-19 patients, troponin T elevation was significantly associated with a greater probability of developing ARDS, arrythmias, and other complications as compared with troponin T within the normal range [
33].
The search of possible therapeutic strategies against SARS-CoV-2 is rapidly proceeding. To date, a number of potential target therapies have been proposed, including angiotensin-converting enzyme 2 (ACE2) inhibitors [
39]. Indeed, ACE2 is a crucial molecule in SARS-CoV-2 infection as viral particle entry into host cell is mediated by S protein interaction with ACE2 [
39]. However, given the current lack of approved specific therapies, COVID-19 treatment is currently based on supportive care, including symptomatic therapies for mild clinical manifestations and respiratory support [
40]. Several drugs approved for other indications as well as multiple investigational agents and potential therapies may provide new opportunities for treating patients infected with SARS-CoV-2. Therapeutic alternatives include specific (remdesivir seems the most promising compound) and non-specific antiviral agents, immune-modulatory agents, other anti-infective agents repurposed to treat COVID-19, and drugs acting on host cell receptors [
39‐
42]. Future clinical studies are needed to highlight the possible pharmacological interactions of some investigational drugs used in the therapy of COVID-19-positive cancer patients with antineoplastic drugs [
43]. Moreover, the search for potential vaccines for COVID-19 is also rapidly progressing.