**1. Introduction**

SARS-CoV-2 has four main structural proteins: the spike protein (S protein), the nucleocapsid protein (N protein), the matrix protein (M Protein), and envelope protein (E protein) [1, 2]. The SARS-CoV-2 infection starts when the virion enters the host's cell, through the connection between the viral S protein and the ACE2 receptor and TMPRSS2 on the host's cells, similarly to severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) [3].

ACE2 and TMPRSS2 are highly expressed in the lungs, partially explaining the high incidence of respiratory disorders. Nevertheless, ACE2 and TMPRSS2 are expressed in many other different organs in the human body, such as the brain, heart, liver, kidney, colonic epithelial cells, intestine luminal cells, and small intestinal enterocytes [4], with reports of SARS-CoV-2 infection on multiple organs [5]. In addition, SARS-CoV-2 may generate a systemic and exacerbated inflammatory response named "cytokine storm", which can lead to viral sepsis [6].

Several systemic biomarkers have been associated with the progression of the disease, such as creatinine, urea, C-reactive protein, ferritin, lactate dehydrogenase, and D-dimers in the blood, increase in the neutrophil-to-lymphocyte ratio, and reduction in platelet count in the blood [7–15]. During COVID-19 the increase in blood levels of chemokines and cytokines increases the pro-inflammatory stimulus and recruitment of immune cells to the infection site. Several risk factors contribute to the disease's severity, such as comorbidities and co-infections [16–18] In this chapter, the current knowledge about the innate and adaptative immune response during COVID-19 and the influence of comorbidities will the reviewed.
