Table 2 Prioritized causal proteins for COVID-19 severity from proteome-wide MR (effects per 1 SD higher plasma protein)
Protein | Gene | Outcome | OR (95% CI) | Dir. | Brief mechanism/evidence |
|---|---|---|---|---|---|
GCNT4 | GCNT4 | Very severe (RS/death) | 1.35 (1.26–1.44) | Risk | O-glycan biosynthesis; mucin/glycome remodeling; MR robust10. |
RAB14 | RAB14 | Very severe (RS/death) | 1.20 (1.10–1.32) | Risk | Endosomal trafficking; viral assembly/egress; MR supported10. |
CD207 (Langerin) | CD207 | Very severe (RS/death) | 1.15 (1.05–1.26) | Risk | DC lectin for viral glycans; MR supported10. |
PECAM1 (CD31) | PECAM1 | Very severe (RS/death) | 0.73 (0.63–0.83) | Prot. | Endothelial junctions; anti-thrombo-inflammation; strong protective MR10. |
ICAM1 (soluble) | ICAM1 | Very severe (RS/death) | 0.80–0.88 | Prot. | Leukocyte adhesion; tissue entry; MR replicated10. |
SELE (E-selectin) | SELE | Very severe (RS/death) | 0.83–0.90 | Prot. | Endothelial activation; protective; panel-dependent10. |
FAAH2 | FAAH2 | Hospitalization | 1.19 (1.12–1.25) | Risk | Lipid mediator turnover; top hospitalization risk MR10. |
IL6R (soluble)† | IL6R | Hosp./severe | modest (dir.) | Prot. | rs2228145 proxies IL-6R inhibition; aligns RCTs9. |
SELL (L-selectin; soluble) | SELL | Very severe (RS/death) | 1.10–1.18 | Risk | Leukocyte trafficking; shedding marks activation; MR robust10. |
ABO glycosyltransferase | ABO | Very severe (RS/death) | 1.10–1.20 | Risk | Blood-group glycosylation; coagulation/adhesion; GWAS/MR supported8,10. |
Neprilysin (NEP) | MME | Hospitalization | 0.80 (0.73–0.87) | Prot. | Degrades vasoactive/inflammatory peptides; protective MR replicated10. |
sICAM1 (soluble ICAM-1)* | ICAM1 | Hospitalization | 0.86 (0.80–0.92) | Prot. | Endothelial/immune adhesion; protective replicated; robust instruments10. |
SELP (P-selectin; soluble) | SELP | Hospitalization / severe | 0.88–1.08 | Mixed | Platelet/endothelial activation; heterogeneous across panels10. |
IL-1 receptor antagonist (sIL-1RA)† | IL1RN | Hospitalization | 0.88–0.95 | Prot. | Anti-IL-1 signaling; protective in MR (panel-dependent)10. |
VCAM1 (soluble)‡ | VCAM1 | Very severe (RS/death) | 0.85–0.95 | Prot. | Vascular adhesion; protective in select panels; mixed sensitivity10. |
Kininogen-1 (high-molecular-weight) | KNG1 | Very severe (RS/death) | 1.08–1.15 | Risk | Contact/coagulation pathway; risk signal in subsets10. |
