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. 2020 Nov 1;202(9):1304-1308.
doi: 10.1164/rccm.202007-2778LE.

Complement Inhibition with the C5 Blocker LFG316 in Severe COVID-19

Wioleta M Zelek  1 , Jade Cole  2 , Mark J Ponsford  1   2 , Richard A Harrison  1 , Ben E Schroeder  2 , Nicholas Webb  3 , Stephen Jolles  2 , Christopher Fegan  1 , Matt Morgan  1   2 , Matt P Wise  1   2 , B Paul Morgan  1
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Free PMC article

Complement Inhibition with the C5 Blocker LFG316 in Severe COVID-19

Wioleta M Zelek et al. Am J Respir Crit Care Med. .
Free PMC article
No abstract available

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Figures

Figure 1.
Figure 1.
Complement activation in severe COVID-19 and response to C5 blockade. (A) Levels of terminal complement complex (TCC; in-house ELISA), C5a (Hycult ELISA), and C5 (in-house ELISA) were measured in ethylenediaminetetraacetic acid (EDTA) plasma from patients with severe COVID-19 and controls; TCC levels were significantly elevated compared with the healthy EDTA plasma controls (COVID-19, n = 25, mean = 12.5 mg/L; controls n = 67, mean = 4.1 mg/L; P < 0.0001, unpaired t test). C5a levels were also significantly elevated compared with healthy controls (COVID-19, n = 25, mean 43.0 μg/L; controls, n = 32, mean = 14.7 μg/L; P < 0.0001, unpaired t test). C5 levels were not different between COVID-19 (n = 25; mean = 84.5 g/L) and controls (n = 31, mean = 81.8 g/L; P = 0.42). Error bars are SE in each panel. Control samples were from a healthy adult donor EDTA plasma set that had previously been collected in the laboratory. (B) Serial trends in PaO2:FiO2 ratio and PaCO2 were measured after LFG316 treatment. Plots represent the means ± 1 SD from arterial blood gas measures taken on the specified day from each of the five patients (labeled below) administered LFG316. Solid squares are PaO2:FiO2 ratios; open circles are PaCO2 levels. Dotted lines indicate grading of acute respiratory distress syndrome (mild: 200–300 mm Hg; moderate: 100–200 mm Hg; or severe: <100 mm Hg); gray zone represents normal range for PaCO2. Rapid clinical improvement in patient 4 leading to extubation on Day 3 after dosing obviated the requirement for additional measures. COVID-19 = coronavirus disease; NS = not significant.
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