Pathophysiology

From ClinicianWiki

Sars-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a β coronavirus. Once inhaled via particles ranging from aerosols to droplets, the spike protein on the virus’s outer surface enables it to bind to the ACE-2 (Angiotensin converting enzyme 2) receptor of host cells in the lung epithelium apical surface. [1] This spike protein is similar to the protein expressed on the surface of Sars-CoV but binds with a much greater affinity. [2] While the S1 subunit of the spike glycoprotein helps with attachment, the S2 subunit aids in the fusion of the viral and the host cell membrane, which allows the virus to enter the lung cell. From there, the viral RNA enters the nucleus for replication, which leads to the production of new viral proteins for viral particles that are released and spread around the body. [1]

Macrophages are situated at the apical epithelium where the virus attacks. This is part of the innate immunity at the alveolar surface. [1] The macrophage recognises the infected cell and is predicted to release cytokine proteins in this process. These include various interleukins (IL-6 specifically), tumour necrosis factor α (TNFα), colony stimulating factors and interferons. The combination of this molecules is predicted in COVID-19 to cause ARDS (Acute respiratory Distress Syndrome) which can be fatal for some patients. The body also has its own chemokine system to suppress the viral infection - in COVID-19 data shows increases in both inflammatory cytokines and circulating chemokines such as CXCL8, CCL2, and CXCL10. [3] Coronavirus Replication Cycle.jpeg

Fig.1 Reprinted from "Coronavirus Replication Cycle", by BioRender, July 2020, retrieved from https://app.biorender.com/biorender-templates/t-5e56d97d1b689000850f8f93-coronavirus-replication-cycle Copyright 2020 by BioRender.

Reference Year Population Intervention Comparison Outcome Level of evidence Strengths Limitations
Koichi Yuki, Miho Fujiogi, and Sophia Koutsogiannaki 2020 N/A N/A N/A upper respiratory symptoms, main symptoms include fever and cough VI summarises pathophysiology of Sars-COV2 Article from April 2020, rapidly evolving knowledge of pathophysiology of COVID-19
Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & Molecular Immunology. 2020;17(6):613-620. 2020 receptor-binding domain (RBD) in SARS-CoV-2 S protein ACE-2 receptor binding investigated human ACE-2 receptors vs bats strong binding to human/bat ACE-2 receptors VI ELISA, flow cytometry, SDS-PAGE and Western Blot, immunofluorescence - range of molecular testing methods Article from March 2020. Recent genomic advances have identified few variable structures.
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine & Growth Factor Reviews. 2020;53:25-32. 2020 N/A N/A N/A N/A VI summarises recent evidence and animal studies on the widespread impacts of the cytokine storm Clinical mentions are in little detail

References

  1. 1.0 1.1 1.2 Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clinical Immunology. 2020;215:108427.
  2. Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & Molecular Immunology. 2020;17(6):613-620.
  3. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine & Growth Factor Reviews. 2020;53:25-32.

Fig1. Reprinted from “Coronavirus Replication Cycle”, by BioRender.com (2020). Retrieved from https://app.biorender.com/biorender-templates BioRender (2020). Coronavirus Replication Cycle. Retrieved from https://app.biorender.com/biorender-templates/t-5e56d97d1b689000850f8f93-coronavirus-replication-cycle