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Global Translational Medicine Immune response in humans due to COVID-19 infection

by tissue tropism in the host. In cases of SARS-CoV-2 3. Immune response against SARS-CoV-2
infection, the main route by which the coronavirus enters variants
the host body is through the angiotensin-converting
enzyme-2 (ACE-2) receptor, which is present on the 3.1. Immune response during the Alpha wave
surfaces of enterocytic, epithelial, and goblet cells in the The VOC, Alpha, or the B.1.1.7 was initially recorded
2
body. Since the spike protein is essential for host evasion, in Kent, UK, in September 2020, following the global
mutations in these regions can significantly change the spread of the original Wuhan strain in March 2020. This
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evasion process, influencing the pathogen’s localization, particular strain follows the general pathway of invasion as
mode of infection, and degree of host defense evasion. discussed earlier. Infection with the Alpha strain severely
3
8,9
As a result, the spread of the virus alters the pattern of the undermines the host’s translational machinery through the
disease in the population, including its clinical severity. action of a non-structural protein (NSP), NSP14. Hijacking
10
However, there exists a distinct subset of patients who of this process disrupts the host’s cellular translation,
have been infected without exhibiting any symptoms allowing the virus to amplify its own genome within the
or experiencing only very mild pathological outcomes. host body. Inhibition of host translation subsequently
Asymptomatic infections have emerged as a potential suppresses the synthesis of antiviral compounds by the
problem in efforts to eradicate the pandemic, as these host, thus compromising the first line of defense—innate
cases represent critical points of transmission that often immunity. Interferon (IFN)-1 has been identified as a
go unnoticed. Recent reports have shedded light on host, key factor in producing an effective reaction against viral
viral, and environmental factors suspected to contribute attack, inducing certain subsets of IFN-stimulated gene
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to this phenomenon. During asymptomatic infection, a (ISG) to inhibit viral replication. Upregulation of ISGs
robust adaptive immune response is generated, which may potentiates the functionality of immune effector cells such
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differ from the attributes of T cell response and antibody as B and T cells, macrophages, and dendritic cells. NSP14
action observed in symptomatic cases. 4,5 targets and disrupts the antiviral response by forming the
NSP14-NSP10 complex as a translation inhibitor, leading
In this review, we aim to elucidate a comparative analysis to the impairment of innate immunity function against
of the infection pathways in the Alpha, Delta, and Omicron the SARS-CoV-2 infection. The undermining of innate
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strains, accompanied by exploring the epidemiological immunity also affects the adaptive immune response.
aspects of their pathogenicity and transmissibility, as well
as their corresponding human immune responses. The adaptive defense against viral attack is enacted
through immune cell-mediated and humoral immunity,
2. Infection and pathogenicity of particularly involving antibodies. However, the contagion
SARS-CoV-2 exhibits a carefully designed pathway to escape from
antibody-mediated neutralization, especially through
As mentioned earlier, SARS-CoV-2 gains entry into the mutations of the spike protein. Neutralizing antibodies
human respiration tract through airborne transmission are highly specific to the viral epitope of the spike’s RBD.
and subsequently infiltrates host cells through the key Mutations in this area notably modify the affinity of
gateway ACE-2 receptor. The receptor binding domain antibodies for the viral epitope, reducing the epitope-
(RBD) of the S1 subunit of spike protein binds to the ACE-2 binding affinity and allowing the virus to escape from
receptor, adopting a trimeric conformation and triggering antibody-mediated neutralization. The N501Y mutation in
the formation of an endosome with a low pH level. the Alpha strain has been identified as the culprit behind a
ACE-2-S1 binding is followed by the cleavage of the S1 and moderately increased escape from neutralizing antibodies
S2 subunits, promoting viral fusion within the endosome. 13,14
Host proteases such as transmembrane protease serine compared to the ancestral strain.
2 (TMPRSS2) cleave multiple furin cleavage sites on the Humoral immunity is extensively intertwined with
spike proteins. Endosomal fusion is further facilitated by cell-mediated immunity. Following the pathogen attack,
extensive protein folding modifications of the spike HR1 heavy production of immunoglobulin IgM and IgG
and HR2 domains of S2 by forming a six-helical structure occurs from B cells in response to antigen presentation,
that physically reduces the distance between the host and typically within 3 – 6 days. IgM serves as the primary
virus, allowing fusion of both membranes. Subsequently, antibody response against viral invasion, while high-
endosomal fusion grants the virus access to the host’s affinity IgG constitutes the secondary response crucial
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cellular machinery, allowing for viral proliferation and the for long-term immunological memory. The release of
budding off of newly synthesized and packaged virions these immunoglobulins eventually leads to an increase
from the infected cell. 6 in inflammatory cytokine levels to combat the pathogen.

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/gtm.2228