Utilizing labour and delivery units for remdesivir infusion for high-risk pregnant and postpartum patients with mild-to-moderate disease during a COVID-19 surge.

In January 2022, as the Omicron variant of SARS-CoV-2 surged globally [1], multiple outpatient therapies showed reduction in hospitalization rates when administered to patients with mild-to-moderate COVID-19 and were recommended for treatment of high-risk individuals by the NIH and IDSA. These therapies included monoclonal antibody treatment (sotrovimab) and antiviral treatment with molnupiravir, nirmatrelvir-ritonavir, or remdesivir [2].

Pregnant individuals with COVID-19 are known to be at increased risk for severe disease, hospitalization, intensive care unit admission, and death [3]. As such, it is particularly important to manage mild-to-moderate COVID-19 in pregnant patients and prevent disease progression if possible. However, none of the clinical trials of outpatient medications included pregnant people. Even if they were considered candidates, severe medication shortages meant that as health systems prioritized the highest risk patients for available treatments, pregnant and postpartum patients fell below the risk threshold to receive these scarce medications.

While remdesivir was widely available during this time, the need for IV administration of three consecutive doses posed significant logistical challenges given constrained infusion beds and nursing staff across the institution.

Given the experience administering remdesivir to pregnant inpatients during earlier waves of the pandemic [4], the desire to offer treatment to pregnant patients at risk for disease progression, and the availability of space, nurses, and pharmacy staff on the labour and delivery unit, we piloted the use of Labour and Delivery (L&D) as an infusion centre for administration of remdesivir to high-risk pregnant patients with COVID-19.

A protocol was created to administer a three-day outpatient course of remdesivir to high-risk pregnant and postpartum patients with mild-moderate COVID-19 in L&D Triage. Patients admitted to L&D for labour and noted to have mild-moderate COVID-19 were offered inpatient treatment.

Patients were considered eligible for treatment if they met all the following criteria: positive COVID-19 test by antigen or PCR testing, mild-moderate COVID-19 symptoms ≤ seven days from onset, pregnant or postpartum (up to four weeks), and ≥ one additional risk factor: unvaccinated or under-vaccinated (partial primary course or absence of booster dose), BMI ≥ 35, diabetes on medication, severe cardiovascular disease, severe immune suppression, chronic kidney, liver, or lung disease, or sickle cell disease.

Patients were treated in L&D Triage if outpatient, or on L&D if inpatient. There were two outpatient appointments available daily. No pre-infusion labs were drawn unless the patient had known underlying liver or kidney disease (if indicated, complete metabolic panel and PT/INR). Vital signs including temperature, blood pressure, heart rate, respiratory rate, and oxygen saturation were monitored. Fetal assessment was conducted based on gestational age (GA). If GA < 24 weeks, fetal heart rate was assessed by Doppler. If 24-28 weeks, fetal movement was assessed; if regular fetal movement, fetal heart rate was monitored by Doppler, if no regular fetal movement, cardiotocography was performed. If GA > 28 weeks, fetus was monitored with cardiotocography.

Infusions were given as 200mg on day one, and 100mg on days two and three. Infusion time was 30 minutes. There was no monitoring post-infusion. If patient did not return for dose two, a second dose was given on the third day and treatment was considered complete—there was no extension beyond three consecutive days.

We treated a total of eight patients under this protocol. See Table I for summary of patient characteristics and outcomes. Seven patients received all three doses of remdesivir, and one patient received only one. No patients progressed to severe disease. No maternal or neonatal adverse events occurred.

Table 1

Characteristics and outcomes of patients treated using protocol to administer remdesivir on Labor & Delivery

Patient	Age	Race	Ethnicity	Language	Gestational agea	Insurance status	Vaccination status	Additional comorbidity present	# RDV Doses received	Days since symptom onseta	Symptoms at initiation of RDV	Treated inpatient or outpatient?	Progression to severe COVID-19 disease?	Neonatal outcomesb
1	33	White	Non-Hispanic	English	PP day 8	Public	Moderna x2	None	3	0	Nasal congestion	Inpatient	No	-
2	21	Other	Hispanic	Spanish	27w6d	Public	Unvaccinated	None	3	1	Nasal congestion, sore throat	2 inpatient, 1 outpatient	No	Term (40w4d); 4.235 kg; 8/9
3	28	Black or African American	Non-Hispanic	English	33w3d	Private	Unvaccinated	BMI ≥ 35, Diabetes on medication	3	3	Cough, sore throat, nasal congestion, muscle aches	Inpatient	No	Preterm (35w6d); 3.375 kg; 9/9
4	23	Asian	Non-Hispanic	English	9w0d	Public	Pfizer x2	BMI ≥ 35	3	5	Cough, shortness of breath, malaise	Outpatient	No	Not yet delivered; U/S at 33w5d with EFW 2.438 kg (58%ile)
5	30	Other	Hispanic	Spanish	PP day 2	Public	Pfizer x1	BMI ≥ 35	3	3	Cough	Inpatient	No	-
6	38	White	Non-Hispanic	English	27w6d	Private	Pfizer x3	Immuno-suppressed (infliximab)	3	3	Nasal congestion, fatigue, cough	Outpatient	No	Term (37w0d); 3.155 kg; 8/8
7	25	Other	Hispanic	English	38w0d	Public	Moderna x1	BMI ≥ 35	3	5	Cough, sore throat, body aches, nasal congestion, SOB	Outpatient	No	Term (39w1d); 2.935 kg; 8/9
8	36	Black or African American	Non-Hispanic	English	PP day 1	Public	Pfizer x2	BMI ≥ 35	1	2	Malaise, fatigue, muscle aches, fever, sore throat, cough	Inpatient	No	-

PP = postpartum; RDV = remdesivir; EFW = estimated fetal weight.

At time of first dose remdesivir.

Gestational age at delivery, birth weight, Apgar scores at 1 and 5 minutes.

Obstetrical units are uniquely positioned to offer remdesivir to pregnant and postpartum patients with mild-moderate COVID-19. This protocol demonstrates a feasible approach to treatment of high-risk pregnant patients when other outpatient medical management options were either in limited supply (nirmatrelvir-ritonavir, sotrovimab) or had concerns for safety in pregnancy (molnupiravir).

As new variants of SARS-CoV-2 continue to emerge, options for therapy and expected efficacy vary. The BA.1 and BA.2 Omicron variants have been shown to be notably less susceptible to monoclonal antibody therapies that were effective against earlier variants [5]. In addition, while nirmatrelvir-ritonavir’s availability has increased since its release, it has many notable medication interactions which may render it inappropriate for some high-risk pregnant patients. While remdesivir for COVID-19 has not been specifically studied in pregnant or lactating people, and thus has uncertain efficacy and potential toxicity, observational data suggests it is safe and well-tolerated [4, [6], [7]]. As such, remdesivir remains an important therapeutic option with a longer track record of use. Our experience demonstrates that obstetrical units can be efficiently used as remdesivir infusion sites.

We conclude that obstetrical units should create a protocol to offer remdesivir to pregnant patients with mild-moderate COVID-19. Given the safety and efficacy of remdesivir in pregnancy and the fact that pregnancy is a risk factor for progression to severe disease, hospitalization, intubation, and death from COVID-19, it is critical to maximize available therapy options for pregnant patients.

Source of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

None.