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COVID-19 research

Gene: CXCL8

Green List (high evidence)

CXCL8 (C-X-C motif chemokine ligand 8)
EnsemblGeneIds (GRCh38): ENSG00000169429
EnsemblGeneIds (GRCh37): ENSG00000169429
OMIM: 146930, Gene2Phenotype
CXCL8 is in 3 panels

2 reviews

Alison Coffey (Illumina Clinical Services Laboratory, Illumina Inc.)

Green List (high evidence)

Publications

Rebecca Foulger (Genomics England curator)

Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor):

• CXCL8 is a proinflammatory chemokine that plays a role in inflammatory response and immune cell trafficking
• Multiple studies show IL-8 levels were shown to be elevated in plasma of patients with COVID-19, SARS-CoV, or MERS-CoV compared to controls. These include a number of recent COVID-19 studies (Coperchini et al. 2020).
• Higher levels were detected in more severe cases (Gong et al. 2020; Qin et al. 2020; Yan et al. 2020), although one study shows the levels are within the normal range (Qin et al. 2020)
• Gong et al. (2020) suggest that IL-8 might be a therapeutic target COVID-19

Literature:
PMID 32446778; Coperchini et al. (2020)
• Review article describing the involvement of chemokine/chemokine-receptor system in COVID-19
• Discusses the concept of cytokine storm where the immune system is ‘attacking’ the body resulting in acute respiratory distress syndrome.
• Multiple studies are mentioned that show high levels of CXCL8 in the plasma and broncho-alveolar fluid in patients with acute respiratory distress syndrome. Reference a paper that notes that pre-treatment with an anti-CXCL8 antibody prevented acute lung injury that generally develops.
• In vivo studies showed elevated CXCL8 in patients with SARS-CoV.
• In vitro studies where peripheral blood mononuclear cells from healthy donor inoculated with SARS-CoV showed enhancement in the expression of CXCL8
• Similarly, CXCL8 was upregulated in cells lysates when with MERS-CoV infection of polarized airway epithelial cells (higher expression than SARS-CoV).
• Higher plasma levels of CXCL8 in patients with COVID-19 compared to healthy controls; however, transcription of CSCL8 was not upregulated

MedRxiv; Gong et al. (2020)
• Evaluated disease severity in a total of 100 patients with COVID-19 pneumonia
• CXCL8 (IL-8 in this paper) was detected in these patients and IL-8 levels were shown to be associated with disease severity (P<0.001); significant differences were noted between critical and severe patients or critical and mild groups (Tables 2 and 3)
• Suggest that IL-8 might be a therapeutic target COVID-19

PMID 32161940; Qin et al. (2020)
• Retrospective study of 452 patients with COVID-19; severity of COVID-19 defined according to the Fifth Revised Trial Version of the Novel Coronavirus Pneumonia Diagnosis and Treatment Guidance
• Clinical and laboratory data were collected
• A majority of the severe cases (n=286) had elevated levels of IL-8 (18.4 pg/mL vs 13.7 pg/mL, respectively; p<0.001) compared to the nonsevere cases (n=166), although they were all in the normal (0-62.0 pg/mL) (Table 2)

MedRxiv; Yan et al. (2020)
• Identified 25 genes that showed highly conserved kinetics in COVID-19 patients
• Figure 3F shows expression of CXCL8 and plasma levels of IL-8 from four individuals with COVID-19 compared to four healthy controls was higher in patients especially in the severe stage (p<0.001)

PMID 15585888; Chang et al. (2004)
• Introduction has a summary of previously published papers and notes that high serum levels of IL-8 were detected during acute phase and associated with lung lesions in patients with SARS in one study. Another study suggests use of corticosteroids in reducing pulmonary inflammation due to IL-8.

• Chang et al. (2004) used transient transfection of the SARS-CoV S protein-encoding plasmid on the IL-8 promoter. Measure of IL-8 release in lung cells showed an upregulation of IL-8 release. In addition, a specific region of the S protein was identified as a potentially important region for inducing IL-8 release.

There are additional case-control studies suggesting possible association of polymorphisms in CXCL8 and acute bronchiolitis susceptibility (Pinto et al. 2017; PMID 27890033), asthma (Charrad et al. 2017; PMID 28993876), or human papillomavirus infection (weaker evidence; Junior et al. 2016; PMID 27783717).
Created: 28 May 2020, 3:28 p.m. | Last Modified: 28 May 2020, 3:28 p.m.
Panel Version: 0.349
Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team. Listed as IL8 gene symbol in OMIM.
Created: 28 May 2020, 2:05 p.m. | Last Modified: 28 May 2020, 2:05 p.m.
Panel Version: 0.339

Details

Mode of Inheritance
Unknown
Sources
OMIM
146930
Clinvar variants
Variants in CXCL8
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 May 2020, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications

Rebecca Foulger (Genomics England curator)

gene: CXCL8 was added gene: CXCL8 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green Mode of inheritance for gene: CXCL8 was set to Unknown Publications for gene: CXCL8 were set to 15585888; 32161940; 3244677