Table 2.

Molecules of interest trapped inside the digested microclots of high-responder long COVID patients (N = 66) vs all controls (N = 29)

Uniprot ID	Molecule	Uniprot description / function if available (as specified on Uniprot website or references in the column)	Fold change	p-Value
Molecules of interest involved in the coagulation system found to be INCREASED in the long COVID sample vs healthy sample
P04275	VWF_HUMAN / von Willebrand factor	Important in the maintenance of haemostasis. It promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII delivering it to the site of injury stabilizing its heterodimeric structure and protecting it from premature clearance from plasma	2.6	9.4 × 10− 11
P02775	CXCL7_HUMAN / Platelet basic protein (LA-PFA4)	LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates the formation and secretion of plasminogen activator by human synovial cells	3.5	3.5 × 10− 05
P08697	A2AP_HUMAN / α(2)-antiplasmin	Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin	1.3	0.0098 (Marginally increased)
Molecules of interest involved in the coagulation system found to be REDUCED in the long COVID sample vs healthy sample
P03952	KLKB1_HUMAN / Plasma kallikrein	The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin	4.4	4.2 × 10− 07
Molecules of interest involved in cellular function found to be INCREASED in the long COVID sample vs healthy sample
Q08380	LG3BP_HUMAN / Galectin-3-binding protein	Promotes integrin-mediated cell adhesion. May stimulate host defence against viruses and tumour cells	2.3	3.9 × 10− 07
P07996	TSP1_HUMAN /Thrombospondin-1	Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp Ligand for CD36 mediating antiangiogenic properties. Plays a role in ER stress response via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors (by similarity.)	2.4	5.1 × 10− 05
P19652	A1AG2_HUMAN / Alpha-1-acid glycoprotein 2	Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction	2.8	2.5 × 10− 25
P19827	ITIH1_HUMAN / Inter-alpha-trypsin inhibitor heavy chain H1	May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization. synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes. Contains a potential peptide which could stimulate a broad spectrum of phagocytotic cells	2.1	1.4 × 10− 17
P19823	ITIH2_HUMAN / Inter-alpha-trypsin inhibitor heavy chain H2	May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes	1.5	8.7 × 10− 09
Molecules of interest involved in cellular function found to be REDUCED in the long COVID vs healthy sample
Q8TDL5	LPLC1_HUMAN / Long palate, lung and nasal epithelium carcinoma-associated protein 1	May play a role in innate immunity in mouth, nose and lungs. Binds bacterial lipopolysaccharide (LPS) and modulates the cellular responses to LPS	4.7	0.0009
P02788	TRFL_HUMAN / Lactotransferrin	Transferrins are iron binding transport proteins which can bind two Fe3+ ions in association with the binding of an anion	2.3	0.006
Q15848	ADIPO_HUMAN / Adiponectin	Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages and also by counteracting its effects, Inhibits endothelial NF-kappa-B signalling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodelling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW	4.9	5.1 × 10− 05
P02763	A1AG1_HUMAN / Alpha-1-acid glycoprotein 1	Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction	5.2	5.0 × 10− 28
Molecules of interest involved in lipid metabolism found to be INCREASED in the long COVID sample vs healthy sample
P02655	APOC2_HUMAN / Apolipoprotein C-II	Component of chylomicrons, (VLDL) very-low-density lipoproteins, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase. Both proapolipoprotein C-II and apolipoprotein C-II can activate lipoprotein lipase. Present in normolipidemic individuals, it is mainly distributed in the HDL, whereas in hypertriglyceridemic individuals, predominantly found in the VLDL and LDL	1.7	3.1 × 10− 06
Molecules of interest involved in lipid metabolism found to be REDUCED in the long COVID sample vs healthy sample
P02652	APOA2_HUMAN / Apolipoprotein A	May stabilize HDL (high density lipoprotein) structure by its association with lipids and affect the HDL metabolism	5.2	1.4 × 10− 14

Fold changes and P values of molecules that were either increased or reduced in the long COVID high responder population compared to controls are shown here (p = 0.012). Descriptions of the function of the molecules are taken from the Uniprot website and added in the description column. Proteomics data was analysed using multiple testing correction and the Benjamini–Hochberg test was performed. The P-value was adjusted to < 0.012, after the Benjamini–Hochberg correction was applied