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

the S1-S2 protein cleavage site of the viral spike protein. coronaviruses and the non-RBD region of Omicron and
Moreover, in addition to its infectivity, the modification of the Wuhan strain, these compartments harbor abundant
this route of infection further reduces the pathogenicity of anti-spike B cells due to pre-pandemic exposure. 50
the contagion. 43 4. Comparison of invasion mechanisms and
Summarizing the evolutionary changes, it is evident that corresponding pathological outcomes in
the antibody-mediated immune response during Omicron
variant infection has been rendered ineffective. However, SARS-CoV-2 variants
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cell-mediated immune response plays a crucial role in Over the course of the pandemic, immune response
fighting Omicron infection, with T cells being considered patterns have shifted in tandem with the fast evolutionary
the primary warriors in this aspect of immunity. Notably, waves of new variants. Understanding the interplay
disease severity is significantly reduced when T cells are between viral pathogenicity and transmissibility has been
activated, as most of the mutations are in the spike protein, paramount for global public health. Hospitalization rates,
which is expected to be incapable of disrupting cell- closely correlated with pathogenicity, have served as a
mediated immunity. In individuals previously exposed key epidemiological metric for tracking the trajectory of
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to SARS-CoV-2 infection, 70 – 80% of T cells were found clinical severity. Communities with higher hospitalization
to be highly cross-reactive to the Omicron variant despite rates often exhibit elevated levels of pathogenicity. Notably,
its significant evasion from antibody neutralization. amino acid changes in the spike protein have been
The distribution of SARS-CoV-2 specific T cell epitopes associated with varying degrees of pathogenicity across
throughout the spike region suggests a response different variants, with the Delta strain exhibiting maximal
predominantly directed toward conserved regions, pathogenicity and the Omicron variant demonstrating the
potentially limiting viral evasion from T cells. However, lowest. As previously noted, mutations in the spike protein
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it must not be overlooked that the Omicron variant efficiently regulate the pathogenicity and transmissibility
possesses 20 additional mutations in other proteins, which of a variant. A study of epidemiological research carried
may evade T cell immunity to some extent. Nevertheless, out in Spain revealed a comprehensive comparative
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the role of CD8 T cells appears promising, although statistical analysis of COVID-19 waves. In comparison
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studies have revealed the abolishment of CD8 recognition with the Delta variant, which peaked in clinical severity
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in 15% of individuals under Omicron infection, possibly due to mutations such as L452R, T478K, and K417N, the
indicating elevated clinical severity in some patients. The Alpha variant demonstrated a 43% drop in hospitalization
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predictions suggest that Omicron’s 29 protein mutations likelihood, while the Omicron variant demonstrated an
alter human leukocyte antigen (HLA) binding and antigen even more significant 72% decrease. 51,52 From a virological
presentation, resulting in changes in the affinity of 143 standpoint, greater attention should be paid to comparing
peptide-HLA class I pairs and 85 peptide-HLA class II the structures of the spike proteins of each variant to
pairs. Strikingly, compared to Delta, Omicron has a much better understand the pathological implications. 53,54 The
greater impact on HLA-peptide binding. Other reports viral genome of the Alpha strain contained 23 mutations,
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provide data that elucidates a significant reduction in both seven of which were deemed critical for the variant’s
CD4 and CD8 T cell responses, with the former showing phenotype, 55,56 while the spike genes of the Delta strain
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a reduction of 14–30% and the latter showing a median contained approximately 13 mutations.
reduction of 17 – 25%. 46 On the other hand, the Omicron variant’s spike protein
Omicron presents a challenge in terms of B-cell exhibits an abnormally high number of mutations (about
immunity escape. However, certain roles of B cells 32 mutations). 57,58 These mutations contribute to the
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remain to be fully understood, as they may play a role increased transmissibility of the variant. Reports indicate
in obstructing the contagion. Long before the pandemic, that mutations such as D614G, H655Y, N679K, P681H,
sequential seasonal coronavirus infections were common G339D, S371L, S373P, S375F, E484A, T951, and G142D
among the human population. Exposure to seasonal are particularly responsible for enhancing the Omicron
coronavirus infections led to the development of two variant’s transmissibility. Moreover, these mutations
sets of cross-reactive, resting switched memory B cells collectively change the Omicron variant’s evasion route,
(CD27 and CD27 ), which existed even before Omicron rendering it more resistant to antibody neutralization than
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41,52
infection. These memory B cells demonstrated cross- its ancestors.
reactivity to non-RBD regions of both Omicron and Figure 1 describes the mechanistic process of Omicron
the wild-type SARS-CoV-2 (Wuhan strain). Given the evasion, contrasting it with the approaches employed by
greater homology between the spike protein of seasonal other common VOCs. The endosomal entry pathway

Volume 3 Issue 1 (2024) 5 https://doi.org/10.36922/gtm.2228