COVID-19

=== Immunopathology ===
[[File:Fimmu-11-579250-g003.jpg|thumb|Key components of the [[Adaptive immune system|adaptive immune response]] to SARS-CoV-2]]

Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID‑19 have symptoms of systemic hyperinflammation. Clinical laboratory findings<!-- Spellings in this paragraph have been meticulously compared link-by-link; if you spot an error, please correct the other article first. --> of elevated [[Interleukin 2|IL{{nbh}}2]], [[Interleukin 7|IL{{nbh}}7]], [[Interleukin 6|IL{{nbh}}6]], [[granulocyte-macrophage colony-stimulating factor]] (GM{{nbh}}CSF), [[CXCL10|interferon gamma-induced protein{{spaces}}10]] (IP{{nbh}}10), [[Monocyte chemoattractant protein-1|monocyte chemoattractant protein{{spaces}}1]] (MCP1), [[CCL3|macrophage inflammatory protein 1{{nbh}}alpha]] (MIP{{nbh}}1{{nbh}}alpha), and [[tumour necrosis factor]] (TNF{{nbh}}α) indicative of [[cytokine release syndrome]] (CRS) suggest an underlying immunopathology.<ref name="Huang24Jan2020" />

[[Interferon-alpha|Interferon alpha]] plays a complex, Janus-faced role in the pathogenesis of COVID-19. Although it promotes the elimination of virus-infected cells, it also upregulates the expression of ACE-2, thereby facilitating the SARS-Cov2 virus to enter cells and to replicate.<ref>{{#invoke:cite journal ||last1=Ziegler |first1=CGK |last2=Allon |first2=SJ |last3=Nyquist |first3=SK |last4=Mbano |first4=IM |last5=Miao |first5=VN |last6=Tzouanas |first6=CN |last7=Cao |first7=Y |last8=Yousif |first8=AS |last9=Bals |first9=J |last10=Hauser |first10=BM |last11=Feldman |first11=J |last12=Muus |first12=C |last13=Wadsworth |first13=MH |last14=Kazer |first14=SW |last15=Hughes |first15=TK |last16=Doran |first16=B |last17=Gatter |first17=GJ |last18=Vukovic |first18=M |last19=Taliaferro |first19=F |last20=Mead |first20=BE |last21=Guo |first21=Z |last22=Wang |first22=JP |last23=Gras |first23=D |last24=Plaisant |first24=M |last25=Ansari |first25=M |last26=Angelidis |first26=I |last27=Adler |first27=H |last28=Sucre |first28=JMS |last29=Taylor |first29=CJ |last30=Lin |first30=B |last31=Waghray |first31=A |last32=Mitsialis |first32=V |last33=Dwyer |first33=DF |last34=Buchheit |first34=KM |last35=Boyce |first35=JA |last36=Barrett |first36=NA |last37=Laidlaw |first37=TM |last38=Carroll |first38=SL |last39=Colonna |first39=L |last40=Tkachev |first40=V |last41=Peterson |first41=CW |last42=Yu |first42=A |last43=Zheng |first43=HB |last44=Gideon |first44=HP |last45=Winchell |first45=CG |last46=Lin |first46=PL |last47=Bingle |first47=CD |last48=Snapper |first48=SB |last49=Kropski |first49=JA |last50=Theis |first50=FJ |last51=Schiller |first51=HB |last52=Zaragosi |first52=LE |last53=Barbry |first53=P |last54=Leslie |first54=A |last55=Kiem |first55=HP |last56=Flynn |first56=JL |last57=Fortune |first57=SM |last58=Berger |first58=B |last59=Finberg |first59=RW |last60=Kean |first60=LS |last61=Garber |first61=M |last62=Schmidt |first62=AG |last63=Lingwood |first63=D |last64=Shalek |first64=AK |last65=Ordovas-Montanes |first65=J |title=SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. |journal=Cell |series=HCA Lung Biological Network |date=28 May 2020 |volume=181 |issue=5 |pages=1016–1035.e19 |doi=10.1016/j.cell.2020.04.035 |pmid=32413319|pmc=7252096 }}</ref><ref>{{#invoke:cite journal ||last1=Sajuthi |first1=SP |last2=DeFord |first2=P |last3=Li |first3=Y |last4=Jackson |first4=ND |last5=Montgomery |first5=MT |last6=Everman |first6=JL |last7=Rios |first7=CL |last8=Pruesse |first8=E |last9=Nolin |first9=JD |last10=Plender |first10=EG |last11=Wechsler |first11=ME |last12=Mak |first12=ACY |last13=Eng |first13=C |last14=Salazar |first14=S |last15=Medina |first15=V |last16=Wohlford |first16=EM |last17=Huntsman |first17=S |last18=Nickerson |first18=DA |last19=Germer |first19=S |last20=Zody |first20=MC |last21=Abecasis |first21=G |last22=Kang |first22=HM |last23=Rice |first23=KM |last24=Kumar |first24=R |last25=Oh |first25=S |last26=Rodriguez-Santana |first26=J |last27=Burchard |first27=EG |last28=Seibold |first28=MA |title=Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium. |journal=Nature Communications |date=12 October 2020 |volume=11 |issue=1 |pages=5139 |doi=10.1038/s41467-020-18781-2 |pmid=33046696|pmc=7550582 |bibcode=2020NatCo..11.5139S }}</ref> A competition of negative feedback loops (via protective effects of interferon alpha) and positive feedback loops (via upregulation of ACE-2) is assumed to determine the fate of patients suffering from COVID-19.<ref>{{#invoke:cite journal ||last1=Tretter |first1=F |last2=Peters |first2=EMJ |last3=Sturmberg |first3=J |last4=Bennett |first4=J |last5=Voit |first5=E |last6=Dietrich |first6=JW |last7=Smith |first7=G |last8=Weckwerth |first8=W |last9=Grossman |first9=Z |last10=Wolkenhauer |first10=O |last11=Marcum |first11=JA |title=Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology. |journal=Journal of Evaluation in Clinical Practice |date=28 September 2022 |volume=29 |issue=3 |pages=415–429 |doi=10.1111/jep.13772 |pmid=36168893|pmc=9538129 |s2cid=252566067 }}</ref>

Additionally, people with COVID‑19 and [[acute respiratory distress syndrome]] (ARDS) have classical [[Serum (blood)|serum]] [[Biomarker (medicine)|biomarkers]] of CRS, including elevated [[C-reactive protein]] (CRP), [[lactate dehydrogenase]] (LDH), [[D-dimer]], and [[ferritin]].<ref>{{#invoke:cite journal || vauthors = Zhang C, Wu Z, Li JW, Zhao H, Wang GQ | title = Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality | journal = International Journal of Antimicrobial Agents | volume = 55 | issue = 5 | pages = 105954 | date = May 2020 | pmid = 32234467 | pmc = 7118634 | doi = 10.1016/j.ijantimicag.2020.105954 }}</ref>

Systemic inflammation results in [[vasodilation]], allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting [[T&nbsp;cell]]s were shown to correlate with the recruitment of inflammatory IL-6-secreting [[monocyte]]s and severe lung pathology in people with COVID‑19.<ref>{{#invoke:cite journal || vauthors = Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F | title = Role of Monocytes/Macrophages in Covid-19 Pathogenesis: Implications for Therapy | journal = Infection and Drug Resistance | volume = 13 | pages = 2485–2493 | year = 2020 | pmid = 32801787 | pmc = 7383015 | doi = 10.2147/IDR.S258639 | doi-access = free | title-link = doi }}</ref> Lymphocytic infiltrates have also been reported at autopsy.<ref name="Cureus" />