Acting on the Th17 pathway may be a successful therapeutic strategy in the SARS-CoV-2-infected subjects with Th17-dominant immune profiles (Figure 1). Open in a separate window Figure 1 Mechanisms of cytokine storm in severe SARS-CoV-2 infection. China. As of June 20, 8,700,000 COVID-19 cases were reported worldwide. More than 450,000 patients died from infection with this new virus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the Coronaviridae family and is correlated to the subgenus Sarbecovirus. This is an enveloped virus comprising a single-stranded positive sense RNA viral genome. Virions are spherical, with the spiked glycoprotein inserted in the envelope . In other viruses of the same family, this protein has been demonstrated to connect to host cellular receptors and to facilitate membrane fusion . After entering the lungs by respiration, SARS-CoV-2- stimulates the activity of immune cells, increases cytokine production, and IKK-IN-1 actives other pathogen resistance mechanisms. Viral RNAs are identified by the innate immune system via three groups of IKK-IN-1 pattern recognition receptors: RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and Toll-like receptors (TLRs), which stimulate the production of interferon (IFN) and trigger anti-viral effectors such as T CD8 + cells, Natural Killer (NK) cells, and macrophages [3,4]. Cytotoxic T lymphocytes (CTLs) are stimulated after identifying infected cells presenting the viral antigens as portions of surface antigen-MHC-I complexes. Efficacious presentation is determined by the correct harboring of antigens by MHC-I IKK-IN-1 molecules through hydrogen bonds and saltCbridge relations that permit great affinity with higher specificity . An immunoinformatic method was employed to recognize IKK-IN-1 major CTL and B cell epitopes in the SARS-CoV-2 surface glycoprotein. The authors recognized five different CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein . SARS-CoV and MERS-CoV infections are characterized by fast and robust initial virus replication with late IFN generation, resulting in disproportionate inflammatory host responses provoking grave lung alterations [7,8]. In the fight between the virus and the human body, the immunity of the subjects reduces, and the virus virulence augments . This causes edema and congestion of the lung, thickening of the interstitial tissue, and augmented exudation in the alveolar space able to cause respiratory failure. The purpose of this review is to analyze cellular and humoral immune changes induced by SARS-CoV-2 and to propose the possibility that such immune changes could be used as prognostic markers of the disease. Finally, we critically consider the various immuno-modifying drugs useful in the treatment of Covid-19 and underline how the immunotherapeutic approach is of fundamental importance for SARS-CoV-2 infection. 2. Immunopathology of SARS-CoV-2 Infection 2.1. Lymphocyte Subpopulations Subsets of CD4+ T cells, CD8+ T cells, B cells, and NK cells play a central role in the functioning of the immune system. Several reports have IKK-IN-1 studied the diverse lymphocyte populations in subjects with SARS-CoV-2 infection. Lymphocyte populations were studied in 44 subjects on admission. The total amount of PRKAA2 T cells, B cells and NK cells was considerably reduced in contaminated group as T cells and NK cells had been below the standard range, while B cells had been within the low level of the guide beliefs. T cells will be the most changed with the viral an infection, fifty percent the low reference point limit around. Nevertheless, the function of Compact disc4+, Compact disc8+ T cells, and NK cells was within regular limitations within this scholarly research, as recommended by PMA/Ionomycin-triggered IFN- positive cells in these three populations. Furthermore, examining the many subsets of T cells, the authors evidenced that both helper (Compact disc3+Compact disc4+) and cytotoxic T cells (Compact disc3+Compact disc8+) had been below the standard range in topics with COVID-19, using the T helper/suppressor proportion (Th/Ts) within regular limits. Furthermore, topics with SARS-CoV-2 an infection showed lower amounts of regulatory T cells (Treg) (Compact disc3+Compact disc4+Compact disc25+Compact disc127low+), which reduction was evident in critical sufferers especially. A reduction in na?ve (Compact disc45RA+Compact disc3+Compact disc4+Compact disc25+ Compact disc127low+) and induced (Compact disc45RO+Compact disc3+Compact disc4+Compact disc25+Compact disc127low+) regulatory T cells was also noticeable in critical.