Pregnancy introduces a heightened vulnerability to severe COVID-19, yet the dearth of data on COVID-19 treatment effects in pregnant women stems from their exclusion from clinical trials [13, 14]. Such data are typically provided by postmarketing studies. The COVID-PR was initiated to accumulate real-world data concerning mAb and antiviral drug utilization in pregnancy for managing mild, moderate, or severe COVID-19. To 13 July 2023, 39 participants were treated with sotrovimab and were followed up for up to 1 year. Many had pre-existing medical conditions linked to the risk of severe COVID-19, such as obesity (29%) and asthma (6%). A total of 75 AEs were recorded, encompassing 31 in study participants and 44 in their offspring. Among these events, 8 in mothers and 16 in infants were classified as serious, but none of these SAEs seemed attributable to sotrovimab treatment. Ten of the maternal non-SAEs were considered attributable to sotrovimab treatment, although most of these were consistent with infusion-site reactions, as highlighted in the sotrovimab prescribing information [17].

A number of studies have provided details on the characteristics of patients who received sotrovimab in a real-world setting. A retrospective analysis of de-identified patients diagnosed with COVID-19 in the US FAIR Health National Private Insurance database included more than 15,000 patients treated with sotrovimab between September 2021 and April 2022 [25]. Among this group, 27.73% had obesity and 4.54% had asthma; other reported comorbidities included chronic kidney disease (10.05%), diabetes (26.11%), and immunocompromising conditions/immunosuppressive therapy (41.74%). A report from the DISCOVER-NOW study (currently published as a preprint), included 696 patients treated with sotrovimab in the UK between December 2021 and May 2022 [26]. In this group, 25.6% had long-term respiratory conditions and 2.3% had obesity.

Research on other mAbs, intravenous immunoglobulin (Ig) G, and plasma validates their risk–benefit profile when used in pregnancy [4, 27,28,29,30,31]. Although pregnant patients were excluded from clinical trials during the development of sotrovimab, other studies of sotrovimab have included pregnant patients. For example, the US Fair Health National Private Insurance database included 1203 pregnant participants, who were analyzed separately. The risk of 30-day all-cause hospitalization or mortality was significantly reduced in pregnant participants who received sotrovimab compared with those who received no mAb [25]. A case series in Japan reported on 60 patients, including three pregnant individuals, treated with sotrovimab during the Omicron era. Although data were not reported separately for the pregnant patients, the overall outcomes were positive; only two patients experienced severe or critical disease progression, no patient required mechanical ventilation or intensive care unit admission, and no deaths were reported [32]. AEs were reported in four patients (6.7%), including infusion-related reaction, liver dysfunction, and post-dose fever in two patients.

An observational study conducted in Qatar assessed the real-world effectiveness of sotrovimab for preventing severe COVID-19 outcomes primarily caused by the Omicron BA.2 variant [33]. The study included 94 pregnant women in the treated group of 340 patients, along with 213 pregnant women among the 1043 untreated controls. Although results for the pregnant participants were not presented separately, an analysis focused on a subgroup at higher risk of severe COVID-19 (which included pregnant participants) revealed a reduction in the risk of disease progression, although statistical significance was not reached. No AE data were included in the report.

A US cohort study in pregnant patients (identified between 30 April 2021 and 21 January 2022) with mild-to-moderate COVID-19 investigated the use of therapeutic COVID-19 mAbs, with sotrovimab being the most commonly administered treatment (n = 382, 69.2%). The study reported mild drug-related AEs in eight (1.4%) mAb-treated patients. There were no differences in obstetric-associated safety outcomes between mAb treatment and no treatment among those who delivered. Additionally, there were no significant differences in 28-day COVID-19-related outcomes or non-COVID-19-related hospital admissions between the mAb treatment and no mAb treatment groups in a propensity score-matched cohort [29].

Tuan et al. [4] reviewed electronic medical records of 22 pregnant patients treated with sotrovimab at the Yale New Haven Health Hospital System and reported that no abortions, fetal losses, or other birth/neurodevelopmental defects were noted.

Three single-case reports from Canada, the United Arab Emirates, and the US described successful outcomes of pregnant women treated with sotrovimab, with resolution of symptoms, no need for emergency care or hospitalization, and no reported fetal or pregnancy-related complications [27, 34, 35].

There are sparse data from this study on pregnancy outcomes. Given the sample size, rare congenital abnormalities are extremely unlikely to be detected, since thousands of exposures would likely be required. Although there was low sample size, there was no indication or pattern of birth defects associated with sotrovimab. Most of the exposures occurred outside of the window of development and confounding factors were present; therefore the outcomes observed were not likely related to sotrovimab administration.

This study has several limitations. First, it was based on a small sample size, and therefore low-frequency AEs are less likely to be detected. As the majority of participants received sotrovimab after the first trimester of pregnancy (the period during which congenital abnormalities are most likely to arise), this may also limit the study’s ability to detect these SAEs. Second, most of the participants came from the US and were treated during a time period when the Omicron variant was dominant [36]. It is therefore unclear how the results of this study relate to other regions, time periods, or COVID-19 variants.

The potential for selection bias and lack of representativeness is another limitation. The enrollment process may introduce biases as participants may self-select to participate based on their experiences or outcomes. This may impact the generalizability of the findings to the wider pregnant population. Additionally, the study faces challenges in recruiting a representative sample due to various factors such as limited access to healthcare and reluctance to participate. Reluctance to receive sotrovimab treatment, particularly due to a perception of the lower severity of current COVID-19 variants, may also limit the number of potential participants available.

Another limitation is the high rate of losses to follow-up, which is a well-recognized challenge for pregnancy registry studies [37, 38]; participants who are lost to follow-up may differ from those who remain in the study, potentially leading to biases in the observed outcomes, which may impact the validity of the results. There is also a high rate of missing information in this study, which may affect the accuracy of the data and limit the ability to draw robust conclusions. Missing demographic variables will restrict the capacity to carry out adjustment in future analyses. Furthermore, many of the AEs are self-reported and not confirmed by a healthcare professional. There is a potential for underreporting, although this is probably more likely for AEs that the participant considers to be less serious. Furthermore, some participants did not provide sufficient information to allow for a comprehensive assessment of the causality of reported AEs. Participants are encouraged to provide medical records, where applicable, and are sent reminders, therefore it is possible that more information may become available in the future.

Finally, there is currently no comparison group for this case series of pregnant patients exposed to sotrovimab. The COVID-PR protocol allows for the recruitment of two comparison groups: an active comparator group who received any medication other than sotrovimab specifically indicated for COVID-19 infection and an unexposed group of hospitalized women who did not receive any specifically indicated treatment. It is hoped they will be available for future analyses.