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Contents: Research Letter

Early Administration of Remdesivir and Intensive Care Unit Admission in Hospitalized Pregnant Individuals With Coronavirus Disease 2019 (COVID-19)

Eid, Joe MD; Abdelwahab, Mahmoud MD; Colburn, Nora MD; Day, Shandra MD; Cackovic, Michael MD; Rood, Kara M. MD; Costantine, Maged M. MD

Author Information
doi: 10.1097/AOG.0000000000004734
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INTRODUCTION

Remdesivir inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Data from clinical trials have demonstrated that remdesivir shortens the time to recovery in hospitalized adults with COVID-19.1–3 Furthermore, earlier treatment initiation (less than 7 days from symptom onset) in high-risk individuals reduces the risk of hospitalization or death.4 The U.S. Food and Drug Administration approved, under an emergency use authorization, the use of remdesivir for patients hospitalized with COVID-19.5 Although data on use of remdesivir among pregnant individuals hospitalized with COVID-19 are limited, its use in pregnant patients has become standard at many hospitals.6 The objective of our study was to investigate whether early administration of remdesivir in pregnant patients hospitalized with COVID-19 was associated with a decrease in intensive care unit (ICU) admission and disease severity.

METHODS

We performed a retrospective cohort study to examine outcomes for pregnant individuals hospitalized with COVID-19 who received remdesivir from April 2020 through October 2021. Infection with SARS-CoV-2 was confirmed by nucleic acid amplification tests. Patients qualified for remdesivir if they were admitted to the hospital with COVID-19, because pregnancy is considered a risk factor for progression to severe or critical disease based on the National Institutes of Health treatment guidelines.7

We compared outcomes of patients who received remdesivir less than 7 days (early group) or 7 or more days (late group) from onset of patient-reported symptoms. The primary outcome was ICU admission. Criteria for ICU admission included hypoxemic respiratory failure, septic shock, multiple organ dysfunction, and hemodynamic instability. Secondary outcomes included need for mechanical ventilation or extracorporeal membrane oxygenation, progression to critical disease, and length of hospital stay. Summary statistics were calculated for baseline variables, and bivariate analyses were performed as appropriate. All statistical analyses were performed using Stata 15. P<.05 was used for statistical significance. The study was approved by The Ohio State University's Institutional Review Board.

RESULTS

A total of 41 hospitalized pregnant individuals received remdesivir, 24 (58.5%) in the early group and 17 (41.5%) in the late group. None of the patients had received any dose of COVID-19 vaccination. Maternal characteristics including age, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), history of preterm birth, and medical comorbidities (including pregestational diabetes, pulmonary disease, and hypertension) were similar between the two groups (Table 1). Gestational age at diagnosis for the early group was higher than that for the late group (34 weeks [interquartile range 29–36] vs 28 weeks [interquartile range 22–32], P=.02).

T1
Table 1.:
Maternal and Coronavirus Disease 2019 (COVID-19) Characteristics*

The early group received remdesivir at a mean of 3 days from onset of symptoms (range 1–6 days), compared with a mean of 9 days (range 7–14 days) in the late group. The majority of patients in our cohort (n=34, 82%) received a 5-day course of remdesivir (range 3–10 days), with no difference in the mean number of doses between the two groups. Using National Institutes of Health criteria, disease severity at the time of first remdesivir dose was similar between the two groups. Patients in the early group were less likely to be admitted to the ICU (21% vs 59%, odds ratio 0.18, 95% CI 0.04–0.72) or to progress to critical disease (12% vs 41%, odds ratio 0.20, 95% CI 0.51–0.87) (Table 2). Additionally, those in the early group had shorter hospital stays (5 days [interquartile range 4–5.75] vs 11 days [interquartile range 4.5–15.5], P<.01). There were two maternal deaths in the late group, compared with none in the early group. Pregnancy outcomes were comparable between the two groups (Table 2).

T2
Table 2.:
Coronavirus Disease 2019 (COVID-19) and Pregnancy Outcomes*

DISCUSSION

Because remdesivir inhibits SARS-CoV-2 viral replication,8 it is plausible that its use in the early stages of the infection might lead to improved outcomes. In nonpregnant patients, early outpatient use of a 3-day remdesivir course was associated with decreased COVID-19–related hospitalization and death, with an acceptable safety profile.4 Our study demonstrated that early administration of remdesivir was associated with improved clinical outcomes, including lower rates of ICU admission and decreased length of hospitalization among pregnant individuals hospitalized with COVID-19. Limitations to our study include nonrandom treatment allocation, which could have led to unmeasured differences between the two groups that may have influenced outcomes. In particular, those in the late group may have had more severe disease, which could have biased our findings. Additionally, our small sample size limited the ability to draw conclusions about low-frequency outcomes. In conclusion, early administration of remdesivir should be considered in hospitalized pregnant individuals owing to risk of severe or critical disease progression.

REFERENCES

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5. National Institutes of Health. COVID-19 treatment guidelines: remdesivir. Accessed January 3, 2021. https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/remdesivir/
6. Burwick RM, Yawetz S, Stephenson KE, Collier AY, Sen P, Blackburn BG, et al. Compassionate use of remdesivir in pregnant women with severe coronavirus disease 2019. Clin Infect Dis 2021;73:e3996–4004. doi: 10.1093/cid/ciaa1466
7. National Institutes of Health. COVID-19 treatment guidelines: clinical spectrum of SARS-CoV-2 infection. Accessed December 11, 2021. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/
8. Wang J, Reiss K, Shi Y, Lolis E, Lisi GP, Batista VS. Mechanism of inhibition of the reproduction of SARS-CoV-2 and Ebola viruses by remdesivir. Biochemistry 2021;60:1869–75. doi: 10.1021/acs.biochem.1c00292

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