Table 1.

Proteomic and metabolomic changes in plasma from severe COVID-19 patients.

Features	Key altered biomarkers	References
Inflammatory responses	↑ APPs (SAA-1, SAA-2, SAA-4, ORM1, ORM2, S100A8/S100A9, SERPINA3, SAP/APCS, CRP, TKT); ↑ LCP1/LPL; ↑CFI	[45, 48–50]
Complement system	↑ C6; ↑CFB; ↑CFP, CPN1; ↑mannose	[45]
Platelet degranulation/coagulation	↓ PPBP, ↓PF4, ↓serotonin, ↓ HRG, ↓GPLD1, CLEC3B; ↓F2; ↓F13A1, F13B; ↓ PROC; ↓SERPINA5; ↑SRGN, VWF; ↑FGA, FGB	[45, 48]
Vessel damage	↑ AGT; ↑FBLN5, NID1; ↑SERPINB1; ↑NRP1; ↓SERPINA4	[48]
Other proteins	Dysregulation of multiple apolipoproteins (APOA1, APOA2, APOH, APOL1, APOD, APOM); ↓ALB; ↓APOA1, APOC1; ↓GSN; ↓TF; ↓FETUB, ↓CETP, PI16; ↑AZGP1; ↑kynurenate, kynurenine	[45, 49]
Amino acid metabolism	↓ >100 amino acids; ↓ arginine metabolism (glutamate, arginine, N-(l-arginino)-succinate, citrulline, ornithine, glutamine, 2-oxoglutarate, N-acetyl-L-glutamate, urea, fumarate); ↓ tryptophan; ↓ valine; ↓ proline; ↓ isoleucine; ↓ carbamoyl phosphate	[4, 45, 47, 72]
Lipid metabolism	↓ lipids, neutral lipids; ↓ sterol, cholesterol; ↓ sphingolipids; ↓ palmitoylcarnitine; ↓ stearoylcarnitine; ↓ oleoylcarnitine; ↓ acylcarnitines; ↓ glycerophospholipids; ↓ choline; ↑ phosphocholine; ↑ 21-hydroxypregnenolone	[4, 49, 59]
Other factors connected to metabolism	↑ HIF-1 signaling pathway; ↑ reactive oxygen species; ↑ lactate dehydrogenase; ↑ succinate; ↓ TCA cycle metabolites; ↓ malic acid; ↓ D-Xylulose 5-phosphate; ↓ guanosine monophosphate; ↓ dihydrouracil; ↓ itaconic acid	[4, 54, 59, 72]

APP activated acute phase protein, SAA serum amyloid A, ORM1 orosomucoid-1/alpha-1-acid glycoprotein-1, SERPINA3 alpha-1-antichymotrypsin, SAP/APCS serum amyloid P-component, CRP C-reactive protein, TKT transketolase, LCP1/LPL lymphocyte cytosolic protein 1/L-plastin, CFI complement factor I, C6 complement 6, CFB complement factor B, CFP properdin, CPN1 carboxypeptidase N catalytic chain, PPBP platelet-expressing chemokines proplatelet basic protein, PF4 platelet factor 4, HRG histidine-rich glycoprotein, GPLD1 glycosylphosphatidylinositol-specific phospholipase D1, CLEC3B C-type lectin domain family 3 member B, F2 prothrombin, F13A1 and F13B thrombin-activation factor, PROC protein C, SERPINA5 serpin family A member 5, SRGN serglycin, VWF von Willebrand factor, FGA fibrinogen alpha, FGB fibrinogen beta, AGT angiotensinogen, FBLN5 fibulin-5, NID1 nidogen 1, SERPINB1 serpin family B member 1, NRP1 neuropilin-1, SERPINA4 serpin family A member 4, APOA1 apolipoprotein A1, APOH apolipoprotein H, APOL1 apolipoprotein L1, APOD apolipoprotein D, APOM apolipoprotein M, APOC1 apolipoprotein C1, ALB albumin, GSN gelsolin, TF transferrin, FETUB fetuin-B, CETP cholesteryl ester transfer protein, PI16 peptidase inhibitor 16, AZGP1 zinc-α2-glycoprotein-1, HIF1A hypoxia-inducible factor 1 subunit alpha, TCA tricarboxylic acid.