INTRODUCTION:

Corona viruses (COVs) are single positive-strand-RNA enveloped viruses classified under broad subgroup Coronavirinae infecting mammals and many species (1, 2).

There are four genera: Alpha, Beta, Gamma and Delta corona viruses. Alpha and Beta corona viruses infect mammals, while Gamma and Delta corona viruses are infecting birds (3, 4).

In December 2019, SARS-COV-2 was detected by sequencing samples taken from a group of pneumonia patients in Wuhan city, CHINA (5, 6). Due to the long incubation time, asymptomatic carriers of the virus, and the extent of individual travel, COVID-19 displayed an astonishing high transmission speed (7).

The virus:

With unique surface projections, corona viruses are huge, roughly spherical (8, 9). A variety of protein molecules are wrapped in an envelope embedded with them (10, 11). When the virus is outside host cell, nucleocapsid shield, membrane proteins, and the virus lipid bilayer envelope protect the virus (12, 13). The viral envelope is composed of lipids bilayer in which structural membrane proteins of spike (S), envelope (E) and membrane (M), are fixed (14-16) as in figure 1

Figure 1: Structure of corona virus

SARS COV-2 binds to the host cell via its spike(S) antigen. The S protein requires host protease priming (17, 18). The cell entry receptor for the SARS-COV2 virus is Angiotensin converting enzyme 2 (19-21).

The SARS-COV2 spike proteins cause ACE2 degradation that contributes to lung damage during viral entry (22, 23). The decrease of ACE2 function aggravates the incidence of pulmonary inflammatory disorders. In older adults, lower levels of ACE2 can lead to more serious clinical activity of COVID-19 (23-25). In older adults, a rise in serum levels of pro-inflammatory cytokines has been identified and has been consistent with pulmonary inflammation (26, 27).

These receptors are expressed by epithelial and by local immune cells like alveolar macrophages (28, 29). Such chemokines attract more innate response cells (neutrophils, NK cells , monocytes dendritic cells (DC), that would secrete chemokines (MCP-1, MIG , and IP-10) able of recruiting lymphocytes that recognize the virus antigen by DCs (30, 31).

The SARS-COV2 virus can infect and replicate pneumocytes of type 1 and type 2 in pulmonary tissue. While the expression of IFN-1, IFN-2 and IFN 3 was induced by SARS viruses, SARS-COV2 didn’t trigger any similar immune mediators and thus was much less effective at inducing other cytokines. Only five cytokines (MCP1, IL-6, CXCL1 , CXCL5 and CXCL10YIP10) induce SARS-COV2 (32).

In covid-19 patients, SARS-COV2 induces a decrease in IFN 1 and IFN3 responses and the secretion of various multiple pro-inflammatory chemokines, IL-6, IL-1B, IL1RA, TNF. This is evidenced by an increase in serum levels of these molecules (33). Cell-mediated immune response and humoral immune response include the immune response to SARS-COV2:

Immune Response mediated by cells:

In patients with covid 19, which is essential for the virus vaccine and for long-term immune response, there are T-cell responses to SARS-COV2 spikes protein that correlate with IgG and IgA antibody titers (34-36).

The inflammatory cells that are mainly essential for viral clearance are CD8+ T-cells. In covid-19, particularly CD+8 T-cells and particularly CD+4\CD+8 ratio, total lymphocytes CD+Tcells, CD+8 T-cells, B-cells and NK cells showed a significant association with inflammatory conditions (37) As in Figure 2

The absolute count of T-lymphocytes, CD+4 T-cells and CD+8 T-cells has decreased in moderate and extreme cases, but more importantly in severe cases (38, 39).

In extreme cases, the expression of INF-Gamma and CD4 T cells is lower than in mild cases (40, 41).

Recognition of the SARS-COVS antigen by cross-reactive and pre-existing T- cells triggered by past human corona virus infection may also lead to the recurrent occurrence of SARS COV2 reactive T-cells in COVID 19 patients (41).

Remarkably, T-cell reactions were observed in people convalescing from mild COVID 19 who had no noticeable SARS-COV2 antibody responses (42).

Humoral immune response:

Antibodies which are directed at viral surface glycoproteins mediate humoral immune responses to SARS-COV2. These antibodies neutralize human cell viral infection that expresses enzyme-converting angiotensin22 (ACE2) (43, 44).

Antigen binding and association with cells carrying Fc gamma-receptors to control consequent immune responses is the key function of neutralizing antibodies.

IgG responses to SARS-COV2 proteins have been shown to be recovered from covid-19 in convalescent serum samples of patients (45). Following infection and vaccination, these neutralizing antibodies to SARS-C0V2 are critical for viral neutralization and viral clearance, which is why antibody titers may be worthy biomarkers for antibody defensive efficacy and humoral immune response after exposure to SARS-COV2 (46).

A study on covid-19 reported that short-term (3-4 months) antibody responses after SARS-COV2 infection (47, 48).

It is crucial to recognize that additional factors affect serological and immune responses during SARS-COV2 infection (race, age, sex ,ethnicity, body mass index, and smoking). They found that IgG titers were higher in older women (40 yrs) compared to younger women (40 yrs) and men (45).

Men express higher anti RBD and antispike glycoprotein neutralizing IgG titers compared to women (49). Sex specific variations in innate, antibody, and T cells responses to SARS-COV2 infection have also been reported. Although men and women have similar prevalence, regardless of age, men infected with COVID 19 are more liable to bad outcomes and death (50).

They observed that old (60-85 yrs) and middle-aged (40-59 yrs) patients had significantly greater expression of SARS-COV2 neutralizing antibody titers than younger patients with respect to age (years 15-39) (50).

Inborn genetic mutations disrupting type 1 interferon responses and genetically induced development of autoantibodies that block type 1 interferon function have been reported as risk factors for extreme covid-19 in a review. The results indicate that such inherent immune response has a vital role in defending against SARS-COV2 infection and in explaining the wide range of phenotypes of clinical diseases (51).

T-cell Detection Assay:

The new T-cell test appears to be more successful in detecting past infections than the antibody test. This measure was found to be higher in symptomatic individuals compared with those without symptoms.

When patients have received the T-cells, they can be sequenced and we can get algorithms or classifiers to identify and diagnose a disease using the computer. They report that the depth and intensity of response of the T-cell was related to the seriousness of the disease, as patients who were symptomatic or hospitalized displayed substantially greater responses than those who were asymptomatic. Conversely, the levels of antibodies were less informative during the post-infection phase because they did not correlate with the intensity of the disease (52).

CONCLUSION:

Covid-19 is correlated internationally with substantial morbidity and mortality, and has a significant impact on health and economic status in the last 100 years.

Due to the existence of the disease, COVID 19 transmitters, like asymptomatic virus carriers, newly infected cases in the incubation period, clinically healed nevertheless still positive for the virus, are difficult to control.

In mild, moderate and extreme cases, the immunology of covid-19 cases is different and develops to more complex as patients progress to a critical disease.

Lymphopenia is crucial as a key underlying mechanism for pathogenesis and as a biomarker of the severity of the disease and a target for therapy.

The vaccine and medicines may be beneficial due to the T and B-cell cross-reactive. In order to contain the disease, chemical antiviral treatments and safe vaccinations can aid. Specific antibody detection is an effective way to diagnose and understand the immunity of the population.

To learn about exposure and immunity, a new T-cell test called the T-Detect Assay will be used and past infections that were overlooked by previous PCR testing will also be reported.

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Received on 09.03.2021 Modified on 30.03.2021

Research J. Pharm. and Tech 2022; 15(1):467-470.

DOI: 10.52711/0974-360X.2022.00076