Table 4 List of genes significantly associated with long COVID in both the Severe and Fatigue Dominant cohorts
Gene | % Patients with corresponding disease signature in Severe cases (Severe controls) | % Patients with corresponding disease signature in Fatigue cases (Fatigue controls) | Gene function | Mechanism of action hypothesis in long COVID |
|---|---|---|---|---|
D2HGDH | 90.6 (12.5) | 70.2 (1.5) | Catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) to alpha-ketoglutarate | Involved in mitochondrial functioning, also exhibits anti-inflammatory effects [29] |
GUCY1A2 | 82.1 (7.9) | 71.9 (1.6) | Guanylate cyclase, catalyzes the conversion of GTP to 3′,5′-cyclic GMP and pyrophosphate | Downregulated (hub gene) in SARS-CoV-2 infection [30] |
PCSK2 | 93.9 (32.9) | 94.9 (10.6) | Proprotein convertase subtilisin, processes hormones, involved in glucagon release | Maintains energy homeostasis, regulates circulating GLP-1 levels [31]. Blood glucose, insulin resistance and diabetes associated with long COVID [32] |
CCDC146 | 92.4 (15.2) | 86.8 (3.7) | Coiled-coil domain containing 146, a ubiquitous centriole and microtubule-associated protein | Associated with cognitive functioning and type 2 diabetes [33] |
PGPEP1 | 82.4 (34.0) | 91.0 (5.7) | Removes 5-oxoproline from various penultimate amino acid residues | Novel, possibly regulates various hormones and neuropeptides |