Table 1.
Complement and cytokine analysis during hospitalization with COVID-19.
| Days | 5,6 | 9 | 11 | 13 | 16 | 17 | 20 | 23 | 27 | 29 | 30 | 34 | 36 | 41 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C3 (83–152 mg/dL) |
111 | |||||||||||||
| C4 (13–37 mg/dL) |
17 | |||||||||||||
| (Free) C5 (13.5–27 mg/L) |
35.9 | 45.5 | ||||||||||||
| CH50 (38.7–89.9 U/mL) |
84 | 61.3 | 68.6 | |||||||||||
| Ba (<1.2 mg/dL) |
>8.72 | 1.8 | ||||||||||||
| Bb (0.49–1.42 mcg/mL) |
2.39 | 4.57 | 2.79 | 2.36 | 2.46 | 1.72 | 0.73 | 1.35 | 1.74 | |||||
| C3a (25–88.2 ng/ml) |
359.9 | >506 | >506 | 409.3 | 411 | 212 | 272.5 | 126.1 | 83 | 88 | ||||
| C3c <2.0 mg/L |
2.8 | |||||||||||||
| C5a (2.74–16.33 ng/mL) |
>40.0 | 36.74 | 33.32 | 36.49 | 35.2 | 33 | >40 | 34 | 31 | |||||
| SC5b-9 (≤ 244 ng/mL) |
1,272 | 355 | 359 | 208 | 314 | 373 | 252 | 440 | 288 | |||||
| sIL2R (175.3–858.2 pg/mL) |
1,140 | 2,852 | 1,996 | |||||||||||
| IF gamma (<4.2 pg/mL) |
<4.2 | <4.2 | <4.2 | |||||||||||
| IL10 (<2.8 pg/mL) |
74 | 13.4 | 5.8 | |||||||||||
| IL1 beta (<6.7 pg/mL) |
<6.5 | <6.5 | <6.5 | |||||||||||
| IL6 (<2.0 pg/mL) |
37.3 | 33.6 | 9.6 | |||||||||||
| IL18 (89–540 pg/mL) |
1,019 | |||||||||||||
| CXCL9 (≤ 121 pg/mL) |
765 | |||||||||||||
| D-dimer (0–220 ng/mL) |
10,000 | 8,985 | 8,106 | 10,000 | 8,705 | 7,064 | 5,338 | 8,598 | 7,622 | 8,434 | 6,732 | 7,803 | 6,099 | 3,690 |
| CRP (<1 mg/dL) |
5.8 | 10.8 | 32.3 | 17.6 | 13.9 | 7.4 | 7.9 | 7.8 | ||||||
| Ferritin (11.1–171.9 ng/mL) |
3,914 | 1,979 | 1,248 | 982 | 856 | 706 | 713 | 562 |
C3, complement component 3; C4, complement component 4; free C5, unblocked complement component 5; CH50, screening test for total complement activity; Ba, complement component fragments Ba; Bb, complement component fragments Bb; C3a, complement component fragment 3a; C3c, complement component fragment 3c; C5a, complement component fragment 5a; SC5b-9, soluble membrane attack complex; sIL2R, soluble interleukin 2 receptor; IF gamma, interferon gamma; IL10, Interleukin 10; IL1 beta, Interleukin 1 beta; IL6, Interleukin 6; IL18, Interleukin 18; CXCL9, Chemokine (C-X-C motif) ligand 9; CRP, C-reactive protein. The whole blood samples for complement testing were collected in EDTA anticoagulant tubes and plasma was obtained within 2 h of collection, and stored in −80°C till they were ready for analysis with single thawing. This method of plasma collection in EDTA results in chelation of calcium and magnesium, thus preventing any in vitro complement activation. All testing was obtained in a CLIA certified hospital-based clinical laboratories. All normal values are in parentheses under each value. Top row signifies the laboratory analyses during the hospital stay.
On days 9, 17, and 29, the samples were collected prior to administration of eculizumab. Complement proteins C3, C4, and C5 signify the quantitative serum levels. As mentioned in Figure 1C, free C5 level on days 11 and 36 measure the free C5 unbound to eculizumab. Factor B is cleaved to Ba and Bb by factor D in the presence of C3b. Fragment Bb is a serine protease that in combination with hydrolyzed C3 (C3H2O) generates C3 convertase (C3bBb), which augments the cleavage of C3 to generate C3a and C3b. Anaphylatoxins, C3a and C5a are involved in local inflammation and tissue/endothelial damage. C5b-9 contributes to intravascular hemolysis and also deposits on cell membranes. Cytokine panel was significant for elevated IL-6 as seen in COVID-19, suggestive of inflammatory/immune response to the virus and the injury. Elevated sIL2R along with IL10, ferritin and CXCL9 are consistent with inflammation seen in COVID-19.