To the Editor: SARS-CoV-2 infection, first documented in Wuhan (China) at the end of 2019, rapidly spread to become a pandemic disease (COVID-19). The infection is highly contagious, and is characterized by a highly heterogeneous clinical phenotype, ranging from fully asymptomatic to severe disease and a high fatality rate [1]. While the reasons for such phenotypic heterogeneity remain ill-defined, some patterns have emerged. In particular, in individuals with severe clinical course, the disease often manifests in two waves [2]. In the first phase, patients present typical clinical symptoms of a respiratory tract infections, whereas in the second phase (approximately 8–12 days after onset of symptoms), sudden worsening of respiratory status occurs. At this stage, diffuse ground-glass opacities are observed on chest computed tomography. Lymphopenia, elevated D-dimer levels, and prolonged prothrombin time are common laboratory abnormalities in these critically ill patients [2, 3]. Although the infection has been documented in subjects of all ages, the mortality rate is particularly high among elderly (> 70 years) individuals. Pre-existing co-morbidities (such as diabetes, hypertension, and chronic lung disease) are associated with worse outcome.

The mechanisms underlying worsening of the disease are object of intense investigation. Increased levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have been documented in severely infected individuals [2–4]. Along with lymphopenia, these observations have led to hypothesize that dysregulation of immune responses may play an important role in the pathology of the disease. However, limited data are available on the immune status of COVID-19 patients. In particular, it remains unknown whether the study of immune parameters at the time of admission to the hospital may help distinguish those who will progress to respiratory failure and will require admission to intensive care units (ICU) and possibly die, from those with moderate symptoms, who will not require invasive ventilation and will eventually recover.