**6. Immunopathology of SARS-CoV2**

Pneumonia, lymphopenia, drained lymphocytes and a cytokine storm are distinguishable symptoms of Extreme Coronavirus Disease 2019 (COVID-19). Major antibody development is detected, but it remains to be determined if this is defensive or pathogenic. Defining the immunopathological changes in COVID-19 patients presents future drug development targets and is critical for clinical management [64]. Asymptomatic condition is found in a large but generally unexplained proportion of the infected people, analogous to many other viral diseases. Usually, a 1-week, self-limiting viral respiratory disease develops in most patients, and ends with the production of neutralizing antiviral T cell and antibody immunity [65]. SARS-CoV-2 has been shown to weaken natural immune responses, resulting in a compromised immune system and an unregulated inflammatory response in extreme and vital COVID-19 patients. These patients display lymphopenia, stimulation and malfunction of lymphocytes, defects of granulocytes and monocytes, elevated levels of cytokines, and higher amounts of immunoglobulin G (IgG) and total antibodies [66] (**Figure 8**). Extreme and fatal COVID-19 is linked with lymphopenia and an elevated amount of blood neutrophils [67]. Lymphocyte counts of 800 cells/μl and a decreased probability of recovery are reported in ICU patients suffering from COVID-19. The mechanism of action and causes of

*SARS-CoV-2 and Coronavirus Ancestors under a Molecular Scope DOI: http://dx.doi.org/10.5772/intechopen.95102*

#### **Figure 7.**

*A phylogenetic tree with all the sequences of SARS- CoV2 available from the 02–Feb-2020 sequence in the blue divisions, plus six Bat coronavirus sequences split in multiple taxa, six human SARS sequences (green) and two MERS sequences (orange); the bootstrap percentage of each branch is recorded [62].*

**Figure 8.** *COVID-19 immunopathology [66].*

lymphopenia in patients with COVID-19 are unclear, but SARS-like viral particles and SARS-CoV RNA have been observed in T cells, indicating that the SARS virus may have a detrimental influence on T cells via apoptosis [68]. Accumulating data proves the involvement of T cells in COVID-19 and possibly in the immunological memory that develops after recovering from infection with SARS-CoV-2. Many, but not always, hospitalized patients tend to have both CD8 + and CD4 + T cell responses, and research points to potential T cell responses consistent with extreme disease that are suboptimal, abnormal or otherwise inadequate [5]. In a report, a group of 452 patients with positive test results of COVID-19 in Wuhan, China shows dysregulated immune system. Boosts in NOD-like receptor (NLR) and T lymphopenia, especially a decline in CD4 + T cells, were prominent in COVID-19 patients, and was even more noticeable in extreme cases, but the number of CD8 + cells and B cells did not change significantly. On the basis of these results, it was proposed that COVID-19 may affect lymphocytes, especially T lymphocytes, and that the immune system is disrupted during the infection period [69]. COVID-19 will lead to defects in the routine of peripheral blood parameters. The most noticeable anomalies that are linked to the intensity of the condition and clinical classification are the reduction in lymphocytes and the rise in the NLR ratio. The lower count and delay in eosinophil development can be indicators of weak COVID-19 outcomes. Thus, complex analysis of peripheral blood routine parameters has a significant reference point for COVID-19 progression and prognosis evaluation [70]. Also, In the different stages of COVID-19, multiple cell morphological modifications can be seen. In fact, a strong granulocytic reaction with immaturity, dysmorphism and apoptotic-degenerative morphology was apparent in peripheral blood in the initial stage of symptom aggravation, typically correlating with hospital entry [71].

*SARS-CoV-2 and Coronavirus Ancestors under a Molecular Scope DOI: http://dx.doi.org/10.5772/intechopen.95102*

Cytokine storm plays a crucial role in infected individuals for the pathogenesis of many serious manifestations of the disease. Acute respiratory distress syndrome, thromboembolic disorders such as acute ischaemic strokes caused by myocardial infarction and large vessel occlusion, encephalitis, acute kidney damage, and vasculitis (childhood Kawasaki syndrome and adult renal vasculitis) [72]. Nonetheless, it is uncertain if serious illness is triggered by immune hyperactivity or inability to overcome an inflammatory reaction owing to continuing virus replication or immune dysregulation. However, records of elevated levels of thrombi production and endothelial cell death in patients with COVID-19 suggest disruption to the vascular endothelium and the participation of cytokine elevated activity and immunothrombosis [73]. In response to infection as well as other triggers, cytokine storm is a general term referring to maladaptive cytokine release. The pathogenesis is complicated, but requires the depletion of regulated control at both local and systemic levels of proinflammatory cytokine output. The disease is rapidly progressing, and mortality is elevated. Some data suggests that dysregulated and uncontrolled cytokine release in certain COVID19 patients has been directly correlated with significant deterioration [74].
