Use of remdesivir for pregnant patients with severe novel coronavirus disease 2019.

Introduction

Coronavirus disease 2019 (COVID-19) has resulted in hundreds of thousands of deaths worldwide. The nucleoside analog remdesivir has shown preliminary efficacy in shortening the duration of moderate and severe COVID-19. , Data from a randomized controlled trial during the Ebola epidemic suggest safety of remdesivir in pregnancy; however, pregnant women have largely been excluded from clinical trials for COVID-19 treatment options. Here, we briefly describe the treatment of 3 pregnant patients hospitalized at our institution with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and imaging supportive of lower respiratory disease, who met the criteria for compassionate use protocol of remdesivir.

Cases

Case A

A 25-year-old pregnant woman at 34 weeks of gestation presented with fever, tachycardia, and tachypnea. Chest x-ray (CXR) revealed patchy consolidations, and nasopharyngeal (NP) swab was positive for SARS-CoV-2 by real-time polymerase chain reaction (Table ). On hospital day (HD) 2, the patient was transferred to the intensive care unit (ICU) for increasing oxygen requirement on nasal cannula. The patient received a total of 3 doses of remdesivir (Figure ), after which additional doses were withheld because of the development of transaminitis. She was ultimately diagnosed with intrahepatic cholestasis of pregnancy (IHCP) in the setting of markedly elevated bile acids. The patient was discharged on HD 8 and underwent an uncomplicated vaginal delivery after scheduled induction at 37 weeks and 2 days of gestation for IHCP.

Table

Laboratory values of pregnant patients with severe COVID-19

Laboratory component	Patient A			Patient B		Patient C
Reference range and units	Admission	Discharge	Delivery	Admission	Discharge	Admission	Discharge
WBC count (4.0–11.0 103/μL)	11.0	6.2	9.4	7.8	8.5	6.6	8.0
Lymphocyte (%)	7.5	28.8	23.2	8.8	21.9	N/A	N/A
CRP (<0.50 mg/dL)	12.20	N/A	N/A	14.29	13.60	N/A	N/A
Troponin (<0.017)	<0.017	N/A	N/A	<0.030	N/A	N/A	N/A
Hemoglobin (11.7–15.7 g/dL)	12.4	12.4	12.0	11.2	11.4	10.9	11.0
Creatinine (0.51–0.95 mg/dL)	0.42	0.28	0.50	0.28	0.39	0.44	0.34
AST (10–35 U/L)	33	457	19	26	16	21	28
ALT (10–35 U/L)	18	432	23	16	14	16	19
Total bilirubin (<1.20 mg/dL)	0.50	0.40	0.30	0.50	0.20	0.40	0.30
Alkaline phosphatase (35–105 U/L)	135	143	116	77	86	77	83
D-dimer (<0.50 ug/mL FEU)	2.54	N/A	N/A	0.77	2.01	1.06	N/A
Ferritin (13.0–150.0 ng/mL)	97.1	N/A	N/A	45.6	63.8	91.0	N/A
LDH (135–214 U/L)	416	688	N/A	190	201	N/A	N/A
Lactate (<2.0 mmol/L)	1.9	N/A	N/A	0.8	N/A	1.0	N/A

ALT, alanine aminotransferase; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; FEU, fibrinogen equivalent units; LDH, lactate dehydrogenase; N/A, not available; WBC, white blood cell.

Igbinosa. Remdesivir for pregnant patients with severe coronavirus disease 2019. Am J Obstet Gynecol 2020.

Figure

Remdesivir dosing protocol

Igbinosa. Remdesivir for pregnant patients with severe coronavirus disease 2019. Am J Obstet Gynecol 2020.

Case B

A 28-year-old pregnant woman at 25 weeks of gestation was transferred to our ICU for COVID-19 pneumonia and acute hypoxic respiratory failure requiring bilevel-positive airway pressure ventilation. Remdesivir was initiated on HD 2, and she received 8 doses of remdesivir. By HD 9, the patient’s supplemental oxygen requirement resolved, and she was discharged home.

Case C

A 29-year-old pregnant woman at 25 weeks of gestation presented with 8 days of fever, headache, cough, and shortness of breath. She was tachypneic and tachycardic on admission. CXR revealed hazy opacities, and NP swab was positive for SARS-CoV-2. She developed hypoxia with oxygen saturation of 88% on ambient air and was placed on supplemental oxygen. A total of 2 doses of remdesivir were administered until clinical improvement, and she was discharged on HD 6.

Comment

As the COVID-19 pandemic continues and pregnant women remain at risk for adverse medical and obstetrical outcomes, having safe and effective therapies, such as remdesivir, is crucial for this population. In our experience, all patients who were receiving supplemental oxygen had resolution of this requirement after initiation of remdesivir. However, a causal relationship cannot be concluded.

Case A underscores that the potential side effect of hepatitis with remdesivir use, which has been reported to be 6% to 8% in the nonpregnant population, , may overlap with pregnancy-related causes of transaminitis, including IHCP; pregnancies of case b and c ongoing at time of this publication. Although this case series is limited in its ability to make broad conclusions, remdesivir was well tolerated in pregnant women and possibly effective. Other than transaminitis, adverse effects of remdesivir were not seen. Corticosteroids were not administered in our patients for maternal or fetal indications. However, recent data demonstrate that dexamethasone may improve outcomes in patients with COVID-19; thus, as indicated for fetal benefit, should be considered for pregnant women with COVID-19.

In each case, the process to obtain remdesivir delayed treatment for our patients by 1 to 2 days. This research highlights the importance of including pregnant women in investigational trials and provision of rapid access to this drug, as pregnant women face increased risk for adverse outcomes in this pandemic.