Autophagy Modulation in Lymphocytes From COVID-19 Patients: New Therapeutic Target in SARS-COV-2 Infection

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the "cytokine storm." Among these, interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF-α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection.

Keywords: CoViD-19; SARS-CoV-2; autophagy; cytokines; lymphocytes.

FIGURE 1

Involvement of autophagy in lymphocyte-mediated inflammation during SARS-CoV-2 infection. Autophagy has a crucial role in the survival, activation, and lymphocyte function. Pro-inflammatory cytokines, secreted during SARS-CoV-2 infection, could influence autophagy contributing to cytokine storm and inflammation. Furthermore, SARS-CoV-2 binding the ACE-2 lymphocyte receptor or the other putative receptors (such as CD147) could play a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could target autophagy.