Figure 2  Immune response in COVID-19 stages. SARS-CoV-2 infection is divided into three general phases. In the first one, called viremia, the virus spreads through the body and there is excessive activation of immune cells with exacerbated production of inflammatory mediators, such as IFN-γ, IL-2, and TNF-α, triggering cytokine storms and immune impairment. The second (acute) phase, characterized by the appearance of COVID-19 symptoms, presents a profile of immune cells still hyperactivated, but with the presence of cell exhaustion markers, such as Tim3, PD1, TIGIT, and NKG2A, in addition to losing the functional capacity of producign IFN, IL-2, and TNF-α. In this period there is still the appearance of CD14+ CD16+ hyperinflammatory monocytes, with a high production capacity of TNF-α, IL-1β, and IL-6, which will migrate to the lungs, contributing to the pathogenesis of respiratory failure and maintaining the cytokine storm. The lethargic state of the immune system in the early stages of infection may be related to the delay in the generation of a humoral response. In the third, or convalescence, phase, the individual can evolve in two opposite directions, recovery or clinical worsening/death. In recovery, cells of lymphoid origin recover their effector function and lose markers of exhaustion, while IgG levels improve. On the other hand, in patients with clinical worsening, this status of immune anergy continues.