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

PROBLEM: We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. METHOD OF STUDY: 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 time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months. CONCLUSION: We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.

Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

Monoclonal Antibodies Casirivimab and Imdevimab in Pregnancy for Coronavirus Disease 2019 (COVID-19).

BACKGROUND: For unvaccinated individuals with mild-to-moderate coronavirus disease 2019 (COVID-19), monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease the risk of severe disease and hospitalization. We describe the use of the monoclonal antibodies casirivimab and imdevimab for COVID-19 in pregnancy. CASE: Two unvaccinated pregnant individuals presented with moderate COVID-19, one in the second trimester and one in third trimester; both met criteria for outpatient management. To decrease the risk for severe disease, they were treated with casirivimab and imdevimab. Neither experienced an adverse drug reaction, and neither progressed to severe disease. CONCLUSION: Monoclonal antibodies such as casirivimab and imdevimab, approved under an emergency use authorization, should be considered in unvaccinated pregnant individuals with mild-to-moderate COVID-19 to decrease the risk of severe disease.

Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE: A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION: Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.