COVID-19

=== Viral and host factors ===

==== Virus proteins ====
[[File:Fpubh-08-00383-g004.jpg|thumb|The association between SARS-CoV-2 and the [[Renin–angiotensin system|Renin-Angiotensin-Aldosterone System]] (RAAS)]]

Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the [[Angiotensin-converting enzyme 2|ACE2]] receptors. It includes two subunits: S1 and S2. S1 determines the virus-host range and cellular tropism via the receptor-binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are [[heptad repeat]] regions. Studies have shown that S1 domain induced [[IgG]] and [[IgA]] antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID‑19 vaccines.<ref name="pmid33340022">{{#invoke:cite journal || vauthors = Dai L, Gao GF | title = Viral targets for vaccines against COVID-19 | journal = Nature Reviews. Immunology | volume = 21 | issue = 2 | pages = 73–82 | date = February 2021 | pmid = 33340022 | pmc = 7747004 | doi = 10.1038/s41577-020-00480-0 |issn=1474-1733 }}</ref>

The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope.<ref name="Boopathi-2020">{{#invoke:cite journal || vauthors = Boopathi S, Poma AB, Kolandaivel P | title = Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment | journal = Journal of Biomolecular Structure & Dynamics | pages = 3409–3418 | date = April 2020 | volume = 39 | issue = 9 | pmid = 32306836 | pmc = 7196923 | doi = 10.1080/07391102.2020.1758788 }}</ref> The N and E protein are accessory proteins that interfere with the host's immune response.<ref name="Boopathi-2020" />

==== Host factors ====
Human [[angiotensin converting enzyme 2]] (hACE2) is the host factor that SARS-CoV-2 virus targets causing COVID‑19. Theoretically, the usage of [[Angiotensin II receptor blocker|angiotensin receptor blockers]] (ARB) and [[ACE inhibitor]]s upregulating ACE2 expression might increase [[morbidity]] with COVID‑19, though animal data suggest some potential protective effect of ARB; however no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain.<ref>{{#invoke:cite journal || vauthors = Kai H, Kai M | title = Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19 | journal = Hypertension Research | volume = 43 | issue = 7 | pages = 648–654 | date = July 2020 | pmid = 32341442 | pmc = 7184165 | doi = 10.1038/s41440-020-0455-8 }}</ref>

The effect of the virus on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a [[systemic inflammatory response syndrome]].<ref>{{#invoke:cite journal || vauthors = Chen HX, Chen ZH, Shen HH | title = [Structure of SARS-CoV-2 and treatment of COVID-19] | journal = Sheng Li Xue Bao | volume = 72 | issue = 5 | pages = 617–630 | date = October 2020 | pmid = 33106832 }}</ref>

Among healthy adults not exposed to SARS-CoV-2, about 35% have [[CD4+ T cell|CD4<sup>+</sup> T cells]] that recognise the SARS-CoV-2 [[Peplomer|S protein]] (particularly the S2 subunit) and about 50% react to other proteins of the virus, suggesting [[cross-reactivity]] from previous [[common cold]]s caused by other coronaviruses.<ref>{{#invoke:cite journal ||vauthors=Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z |date=4 September 2020 |title=Immunological considerations for COVID-19 vaccine strategies |journal=Nature Reviews Immunology |volume=20 |issue=10 |pages=615–632 |doi=10.1038/s41577-020-00434-6 |pmid=32887954 |pmc=7472682 |issn=1474-1741}}</ref>

It is unknown whether different persons use similar antibody genes in response to COVID‑19.<ref>{{#invoke:cite journal || vauthors = Zhang Q, Ju B, Ge J, Chan JF, Cheng L, Wang R, Huang W, Fang M, Chen P, Zhou B, Song S, Shan S, Yan B, Zhang S, Ge X, Yu J, Zhao J, Wang H, Liu L, Lv Q, Fu L, Shi X, Yuen KY, Liu L, Wang Y, Chen Z, Zhang L, Wang X, Zhang Z  | title = Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2 | journal = Nature Communications | volume = 12 | issue = 1 | pages = 4210 | date = July 2021 | pmid = 34244522 | pmc = 8270942 | doi = 10.1038/s41467-021-24514-w | bibcode = 2021NatCo..12.4210Z | s2cid = 235786394 }}</ref>