Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series

Abstract

Problem:We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. Method ofStudy: Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes. Results: Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Do Anti-SARS-CoV-2 Monoclonal Antibodies Have an Impact on Pregnancy Outcome? A Systematic Review and Meta-Analysis

“…We identified 53 articles, 28 of which were assessed with respect to their eligibility for inclusion and 17 studies ultimately included in the systematic review ( Table 1 , Figure 1 ) [ 30 , 32 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Eight studies came from the United States of America (USA), four from Europe, three from Japan and the other two studies were from the United Arab Emirates (UAE).…”

Hyper‐inflammation and complement in COVID‐19

“…High plasma levels of soluble C5b-9 (sC5b-9), C5a, and C4d are found in patients with severe disease and respiratory failure. 4131,42 In addition, decreased serum concentrations of C3 and C4 are associated with disease severity and mortality, probably reflecting complement consumption. 9,43 Pulmonary, skin, and autopsy samples of COVID-19 patients showed C5b-9, C4d, and MASP-2 deposition associated with thrombotic microvascular injury.…”

“…Thrombotic events in both arterial and venous sites are a common complication in patients with COVID-19 and account for high morbidity and mortality. 42 It can occur despite routine thromboprophylaxis, suggesting that there may be intrinsic thrombophilic mechanisms related to SARS-CoV-2 infection. Biopsy and postmortem examination of COVID-19 patients reveals microthrombi in the lungs (associated with septal capillary injury), skin, heart, liver, and kidneys, primarily glomerular capillaries.…”

“…Thrombotic events in both arterial and venous sites are a common complication in patients with COVID‐19 and account for high morbidity and mortality 42 . It can occur despite routine thromboprophylaxis, suggesting that there may be intrinsic thrombophilic mechanisms related to SARS‐CoV‐2 infection.…”

“…The severity of COVID‐19 appears to be directly associated with the intensity of complement activation. High plasma levels of soluble C5b‐9 (sC5b‐9), C5a, and C4d are found in patients with severe disease and respiratory failure 4131,42 . In addition, decreased serum concentrations of C3 and C4 are associated with disease severity and mortality, probably reflecting complement consumption 9,43 .…”