Immunopathology of SARS-CoV-2 Infection: Immune Cells and Mediators, Prognostic Factors, and Immune-Therapeutic Implications

Abstract

<jats:p>The present is a comprehensive review of the immunopathology of Covid-19. The immune reaction to SARS-CoV-2 infection is characterized by differentiation and proliferation of a variety of immune cells with immune mediator production and release, and activation of other pathogen resistance mechanisms. We fully address the humoral and cellular immune changes induced by the virus, with particular emphasis on the role of the “cytokine storm” in the evolution of the disease. Moreover, we also propose some immune alterations (i.e., inflammatory parameters, cytokines, leukocytes and lymphocyte subpopulations) as prognostic markers of the disease. Furthermore, we discuss how immune modifying drugs, such as tocilizumab, chloroquine, glucocorticoids and immunoglobulins, and blood purification therapy, can constitute a fundamental moment in the therapy of the infection. Finally, we made a critical analysis of a number of substances, not yet utilized, but potentially useful in SARS-CoV-2 patients, such as IFN lambda, TNF blockers, ulinastatin, siponimod, tacrolimus, mesenchymal stem cells, inhibitors of mononuclear macrophage recruitment, IL-1 family antagonists, JAK-2 or STAT-3 inhibitors.</jats:p>

SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 patients

“…Patients hospitalized in the pneumology ward (n = 27) and ICU (n = 24) were matched for sex and age, the presence of co-morbidities and the time elapsed from the day of onset of symptoms to first serum sample collection (Table 1). As expected, ICU patients were hospitalized for longer periods and the median serum levels of several proinflammatory biomarkers, (LDH, dimer-D and IL-6) were significantly higher in ICU patients, further confirming their association with COVID-19 severity [2][3][4][5]. Four ICU patients died.…”

“…Here, in addition to further characterizing the antibody response to SARS-CoV-2 in hospitalized COVID-19 patients, we mainly aimed to determine whether a relationship could be established between the magnitude of SARS-CoV-2 RBD IgG and NtAb levels and the "inflammatory state" of patients, which has been shown to directly correlate with COVID-19 severity and prognosis [2][3][4][5].…”

“…Disregulated synthesis and release of pro-inflammatory cytokines is thought to be a pathogenetic hallmark of most severe forms of COVID-19 [4,5]. Although the mechanisms of COVID-19-induced lung injury remain unclear, the so-called "cytokine storm" may likely play a critical role in the process of disease worsening and thus in COVID-19 prognosis [40].…”

“…Clinical presentation of COVID-19 varies widely, ranging from asymptomatic to mild or severe forms [2,3]. Worse clinical outcomes are related to an imbalanced immune response skewed toward a Th 1 pro-inflammatory profile, which leads to the uncontrolled release of cytokines and chemokines, such as interleukin-6 (IL-6), that mediates progression into acute respiratory distress syndrome, multiorgan failure, and death [4,5].…”

Characteristics of Peripheral Blood Cells in COVID-19 Patients Revealed by a Retrospective Cohort Study

“…Although our understanding of the speci c innate and adaptive immune response to SARS-CoV-2 is relatively limited, the hematological changes may re ect a homeostatic mechanism to prevent systemic over-activation of in ammation. SARS-CoV-2 RNA and proteins interact with various pattern recognition receptors can initiate antiviral immune responses which characterized by differentiation and proliferation of various immune cells with immune mediator production and release, especially lymphocytopenia and elevated level of IL-1β, IFN-γ, IP-10 and IL-17, regulating viral replication and spreading within the host [18,19]. SARS-CoV-2 has been proven to induce remodeling of peripheral lymphocytes, and a more robust humoral immune response occurs in severe infection [20].…”