Infection The virus has the ability to enter its target cells through two distinct pathways: an endocytic way that finishes in the endosomal region, in addition a membrane called the plasma membrane pathway located on the outermost layer of the cell. The integration between the viral and plasma membranes was an essential step for the two techniques, as it facilitated the passage of viral genetic material toward the cytoplasm (Shang et al.,2020). Similarly, SARS-CoV-2 infection causes the production of fusogenic S glycoprotein on the host cell membrane, which promotes cell-cell fusion by interacting with ACE2 on adjacent cells (Buchrieser et al., 2020).

       During the infection caused by SARS-CoV-2, host cells release several different kinds of inflammatory mediators. These molecules play a crucial role in encouraging cellular inflammation in addition facilitating natural immune responses. this occurs when tissue-resident immune system cells detect the presence of the virus, leading to the initiation of a centralized innate response (Schultze and Aschenbrenner , 2021).

         The complement pathway, which plays a role in bringing together both adaptive and innate immune responses, is also considered to be part of the immune system natural reaction for SARS-CoV-2 (Ricklin et al., 2010). The activation of the complement pathway in individuals with COVID-19 can be linked to various physiological responses, including coagulation in the vascular system, malfunction of endothelial cells, with the presence of both chronic as well as acute inflammatory disorders (Jin et al., 2020).

       Moreover, T and B lymphocytes cooperate in combating infection by viruses, though with distinct functions. B cells are responsible for triggering the creation of antibodies, which possess the ability to directly recognize viral protein molecules. This recognition mechanism serves the purpose of impeding viral infection of specific target cells. T cell lymphocytes specifically recognize Major Histocompatibility Complex (MHC) classes I and II molecules solely when they are bound to viruses. T and B cells work together to fight viral infections, but they do not do the same thing. B cells produce antibodies that can directly identify viral proteins in order to prevent viruses from infecting the desired cells. T cells identify Major Histocompatibility Complex (MHC) classes I and II molecules only in association with viral proteins, not directly. Every nucleated cell in the body has a different amount of MHC-class I molecules on their surface, and these molecules transport viral proteins generated inside the cells. As a result, T lymphocytes (CD8 cytotoxic T cells) that detect MHC-class I molecules complexed with viral peptides target cells where viruses are reproducing specifically. CD8 T lymphocytes play a direct role in viral production inhibition and infection control by lysing virus-infected cells or secreting antiviral cytokines (Hangartner et al., 2006; McMahan et al., 2021). A separate function is performed by CD4 helper T cells, which are T cells that identify viral proteins associated to MHC-class II. MHC-class II is expressed only by professional antigen-presenting cells, such as dendritic cells, monocytes, and macrophages, which are not infected yet present viral antigen ingested from the environment. T-helper cells (or CD4 T cells) release a number of cytokines (IL-2, IL 21, Interferons, and Tumor Necrosis Factor (TNF)-alpha) after recognizing viral antigen presented by expert antigen-presenting cells, which essentially aid in the creation and proliferation of CD8 T and B cells (McMahan et al., 2021).

       Follicular helper T (TFH) cells, a type of the helpers B cell with specific functions, along with the proinflammatory TH17 cell subset, and regulatory T (TReg) cells, which have crucial role in preventing overactive immune reaction and corresponding immunopathology (Lund et al., 2008). If SARS-CoV-2 is abnormally effective, it can escape early innate immune responses, and consequently the occurrence of the disease (Sette and Crotty, 2021).

References
-------------

Buchrieser, J., Dufloo, J., Hubert, M., Monel, B., Planas, D., Rajah, M. M., et al.  (2020). Syncytia formation by SARS-CoV-2-infected cells. The EMBO journal, 39(23), e106267. https://doi.org/10.15252/embj.2020106267

Hangartner, L., Zinkernagel, R. M., and Hengartner, H. (2006). Antiviral antibody responses: the two extremes of a wide spectrum. Nature reviews. Immunology, 6(3), 231–243. https://doi.org/10.1038/nri1783

Jin, Y., Ji, W., Yang, H., Chen, S., Zhang, W., and Duan, G. (2020). Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. Signal transduction and targeted therapy, 5(1), 293. https://doi.org/10.1038/s41392-020-00454-7

Lund, J. M., Hsing, L., Pham, T. T., and Rudensky, A. Y. (2008). Coordination of early protective immunity to viral infection by regulatory T cells. Science (New York, N.Y.), 320(5880), 1220–1224. https://doi.org/10.1126/science.1155209

McMahan, K., Yu, J., Mercado, N. B., Loos, C., Tostanoski, L. H., Chandrashekar, A., et al. (2021). Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature, 590(7847), 630–634. https://doi.org/10.1038/s41586-020 03041-6

Ricklin, D., Hajishengallis, G., Yang, K., and Lambris, J. D. (2010). Complement: a key system for immune surveillance and homeostasis. Nature immunology, 11(9), 785–797. https://doi.org/10.1038/ni.1923

Schultze, J. L., and Aschenbrenner, A. C. (2021). COVID-19 and the human innate immune system. Cell, https://doi.org/10.1016/j.cell.2021.02.029 184(7), 1671–1692.

Sette, A., and Crotty, S. (2021). Adaptive immunity to SARS-CoV-2 and COVID- 19. Cell, 184(4), 861–880. https://doi.org/10.1016/j.cell.2021.01.007

Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., et al. (2020). Cell entry mechanisms of SARS-CoV-2. Proceedings of the National Academy of Sciences of the United States of America, 117(21), 11727–11734. https://doi.org/10.1073/pnas.2003138117