Table 5 List of genes that were uniquely associated with the Severe case cohort
Gene | % Patients with corresponding disease signature in Severe cases (Severe controls) | Gene function | Mechanism of action hypothesis in long COVID |
|---|---|---|---|
ADIPOQ | 67.1 (20.6) | Adiponectin | Controls fat metabolism and insulin sensitivity [34] Prevents SARS-CoV2-induced acute lung injury [35] |
C1orf50 | 88.0 (9.6) | Chromosome open reading frame 50 | Novel |
CETP | 72.3 (5.6) | Cholesteryl ester transfer protein | Role in insulin resistance, metabolic syndrome, macrophage-induced inflammation [36] |
CPLX4 | 71.2 (4.8) | Complexin 4 | Novel |
DLC1 | 26.8 (3.3) | GTPase, deleted in liver cancer 1 | Autophagy [37], oncogene |
DSCAML1 | 47.3 (2.3) | Down syndrome cell adhesion molecule like 1 | Regulates corticotropin-releasing hormone in HPA axis, attenuated response to acute stressors [38] |
ENSG00000283580 | 88.0 (9.6) | Novel protein | Novel |
ENSG00000285082 | 52.3 (6.5) | Uncharacterized protein | Novel |
ETS1 | 30.5 (1) | Transcription factor, v-ets avian erythroblastosis virus E26 oncogene homolog 1 | Differentially regulated in peripheral blood of severe COVID-19 patients, modulates cytokine response [39,40,41] |
MARCH8 | 74.5 (5.8) | Membrane-associated ring finger, ubiquitin protein ligase | Downregulates host transmembrane protein, confers resistance to multiple viruses including SARS-CoV [42, 43] |
NOL4 | 37.7 7.6) | Nucleolar protein 4 | Differentially expressed in infective endocarditis [44] |
PDE6C | 39.7 (8.3) | Phosphodiesterase 6C, cGMP-specific | Novel |
PGPEP1 | 82.4 (34) | Pyroglutamyl-peptidase I | Novel |
SNX9 | 41.2 (9.7) | Sorting nexin 9 | Regulated by chronic inflammation, trafficking of mitochondrial-derived vesicles [45, 46] |
TLR4 | 52.3 (6.5) | Toll-like receptor 4 | Mediates innate immune response, genetic link to long-term cognitive dysfunction post COVID-19 [47, 48] |