Immunology

Novel Corona virus (COVID-19)

Corona viruses are positive sense single stranded RNA viruses that cause infection in nose, sinuses, or upper throat. It belongs to family of SARS and MERS. COVID-19 is the illness caused by SARS-COV-2, first outbreak occur Wuhan city in China. The pathogenesis of COVID-19 is not defined but reports from many countries indicate that the virus has the same mechanism by which it enters or invades host cells as SARS-COV. The origin of SARS-CoV-2 is not well-established, however, it is established that bats are the source of related viruses and that human to human transmission plays a critical role in its pathogenesis  After entering into target cells following Spike protein association with its receptor , viral RNA is encapsulated and polyadenylated, and encodes various structural and non-structural polypeptide genes. These polyproteins are cleaved by proteases that exhibit chymotrypsin-like activity. Although transmembrane serine protease 2 (TMPRSS2) is the major protease associated with CoV activation and has been linked to SARS-CoV-2 activation, recent evidence from single cell RNA-sequencing (scRNA-seq) analysis shows that ACE2 and TMPRSS2 are not expressed in the same cell suggesting the involvement of other proteases such as cathepsin B and L in this process.

In general, pattern recognition receptors (PRRs) recognize invading pathogens including virus’s .Viruses elicit several key host immune responses such as increasing the release of inflammatory factors, induction and maturation of dendritic cells (DCs) and increasing the synthesis of type I interferons (IFNs), which are important in limiting viral spread. Both the innate and acquired immune response are activated by SARS-CoV-2. CD4 + T cells stimulate B cells to produce virus-specific antibodies including immunoglobulin (Ig) G and IgM and CD8 + T cells directly kill virus-infected cells (Figure 1). T helper cells produce pro-inflammatory cytokines and mediators to help the other immune cells. SARS-CoV-2 can block the host immune defense by suppressing T cell functions by inducing their programmed cell death e.g., by apoptosis. Furthermore, the host production of complement factors such as C3a and C5a and antibodies are critical in combating the viral infection

In patients with COVID-19, the white blood cell count can vary between leukopenia, leukocytosis, and lymphopenia, although lymphopenia appears to be more common Importantly, the lymphocyte count is associated with increased disease severity in COVID-19 Lymphopenia and lower lymphocyte counts indicated a poor prognosis in COVID-19 patients ICU patients suffering from COVID-19 have lymphocyte counts of 800 cells/μl and a reduced chance for survival. The etiology and mechanisms of lymphopenia in COVID-19 patients is unknown but SARS-like viral particles and SARS-CoV RNA has been detected in T cells suggesting a direct effect of SARS virus on T cells potentially through apoptosis