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. 2021 Sep 22;20(10):4627–4639. doi: 10.1021/acs.jproteome.1c00475

Table 2. Diagnostic and Prognostic Protein Biomarkers of COVID-19.

biomarker diagnostic/prognostic matrix cohort platform reference
RPQGLPNNTASWFTALTQHGK (peptide originating from SARS-CoV-2 nucleoprotein) Diagnostic Gargle Proof of concept study Targeted LC-MS/MS (PRM) Pharmafludics-Orbitrap Fusion Tribrid. 3 h Gradient (43)
SARS CoV-2 RNA extracts Diagnostic Respiratory swab n = 36 COVID pos vs n = 42 respiratory disease control Lateral flow-based assay (40 min turnaround) (87)
IgG, IgA, and IgM Diagnostic Whole Blood (DBS) n = 31 DBS serum matched (COVID) 17 DBS only healthy ELISA 10.3201/eid2612.203309(88)
Nucleocapsid protein of SARS-CoV-2 Diagnostic Urine 239 COVID pos (Wuhan) and 20 from Chongqing Immunochromatographic assay 10 min turn around 10.1101/2020.03.07.20032524(89)
Adjunctive test viral RNA and IgM and IgG Diagnostic only: antibodies concentrations exhibited no differences among three (moderate, severe, critical) subgroups Nasopharyngeal swabs and serum samples 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups ELISA + RT-PCR 10.1016/j.intimp.2020.106746(90)
(CSF white blood cell count, neopterin, β2-microglobulin (β2M), and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL] detected... CSF n = 6 moderate to severe light beam analyzer and immunoassay 10.1212/WNL.0000000000010977(91)
List of proteins associated with altered coagulation and complement and IL-6 pathways Diagnostic serum n = 49 of which 33 were COVID-19 positive timsTOF Evosep 10.1021/acs.jproteome.0c00365(37)
27 proteins complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6 Prognostic serum and plasma n = 199 LC-MS/MS SWATH 10.1016/j.cels.2020.05.012(92)
Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease Prognostic Urine n = 12 severe, n = 13 moderate, n = 33 mild Immunoassay 10.1097/CCE.0000000000000170(93)
IL-6 strong predictor of fatal outcome Prognostic Blood test n = 611 included. Analysis on n = 433 Flow cytometry 10.1016/j.jaci.2020.07.009(36)
IL-6 correlated with CT results, also patients with severe disease showed significantly elevated level of D-dimer, ESR, LDH, CRP, and ferritin than those with nonsevere disease Prognostic Plasma n = 69 severe ELISA 10.15252/emmm.202012421(39)
IL-2, IL-6, IL-8, IL-10 increased in severe cases; Lymphocyte count decreased with increased severity, IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness Prognostic Serum n = 168 mild, n = 169 severe, n = 52 critical ELISA 10.1111/cei.13450(35)
Chemical parameters of urine such as urine occult blood (BLOOD), proteinuria (PRO), bilirubin, urobilinogen, potential of hydrogen (pH), specific gravity (SG), ketone (KET), urine glucose (GLU-U), nitrite and leukocytes (LEU) Prognostic Urine 45 healthy, 67 mild, 42 severe, 10 critical Chemical parameters of urine such as urine occult blood (BLOOD), proteinuria (PRO), bilirubin, urobilinogen, potential of hydrogen (pH), specific gravity (SG), ketone (KET), urine glucose (GLU-U), nitrite, and leukocytes (LEU) 10.1515/cclm-2020-0220(94)
56 proteins distinguish between mild and severe: pathways = complement activation, regulation of immune response, cellular oxidant detoxification, cellular response to hypoxia, and oxidative stress induced apoptosis Prognostic Urine 32 healthy, 6 COVID-19 pos: 3 severe, 3 mild LC-MS/MS (Lumos DDA) 10.1101/2020.05.02.20088666(95)
93 proteins and 204 metabolites differentially expressed between severe and nonsevere Prognostic Serum n = 28 healthy, n = 25 disease control, n = 37 nonsevere, n = 28 severe DDA QeHFx and for metabo-UPHLC and waters instrument 10.1016/j.cell.2020.05.032(33)
Peptide Sequences for Nucleoprotein (DQVILLNK + ADETQALPQR) and Spike Glycoprotein (NIDGYFK + FQTLALHR) Diagnostic Culture Lung Epithelial Cell Mucus Secretions Proof of concept study LC-MS/MS DDA and PRM (Q-Exactive HF-X) 10.1021/acs.analchem.0c02288(96)
Machine-learning-based selection of 11 proteins with combinations for clinical outcome prediction; COVID-19 positive vs Healthy prediction [orosomucoid-1/alpha-1-acid glycoprotein-1(ORM1/AGP1), ORM2, fetuin-B (FETUB), and cholesteryl estertransfer protein (CETP)]; Severity prediction with or without fatal outcome (CETP, S100A9, C-reactive protein); Mild vs Severe Symptom Outcome Prediction [zinc-a2-glycoprotein 1 (AZGP1), ORM2, and complement factor I (CFI)]; Convalescence prediction [serine proteinase inhibitor A3/a1-antichymotrypsin (SER-PINA3/ACT), lymphocyte cytosolic protein 1/L-plastin (LCP1/LPL), and peptidase inhibitor 16 (PI16)]; Host plasma protein alterations (Elevated ORM1, ORM2, S100A9, CRP, AZGP1, CFI, SERPINA3/ACT, LCP1/LPL; Reduced FETUB, CETP, and PI16) Prognostic Plasma Initial cohort for Machine Learning: n = 30 (Fatal outcome = 5; Severe symptoms = 7; Mild symptoms = 10; Healthy patients without COVID-19 = 8); Expanded cohort for biomarker validation: n = 160 (fatal = 40, severe = 40, mild = 40, healthy = 40) Tandem Mass Tag DDA LC-MS/MS (Q-Exactive HF-X) (32)
COVID20: 20 urinary peptides for prognosis of critical and fatal outcomes of COVID-19 disease Prognostic Urine Pilot: COVID-19 patients (n = 15), Matched controls (n = 45) P/ACE-MDQ CE micrOTOF and Dionex Ultimate 3000 RSLS nanoflow system or Beckman CE, with Orbitrap Q Exactive plus (44)
Early disease stage inflammation-associated proteins and sustained apoptosis and hyperinflammation-associated proteins differentiate severe (ICU) from moderate (non-ICU) patients [ICU have elevated OSM, S100A12, IL-6, HGF, and CCL7] and distinguish hospitalized (ICU and non-ICU) from healthy controls [hospitalized have elevated CASP8, IFNγ, IL-18R, and CCL8] Prognostic Plasma n = 15 severe, n = 25 moderate, n = 119 healthy controls (n = 18 clinical blood analyses, n = 18 plasma proteins, n = 70 antibody reactivities) Olink and Legendplex (42)