The use of remdesivir among pregnant women and associated clinical outcomes in mother and the child

Marzban-Rad, Saeid; Ghafarzadeh, Masoumeh; Bahmani, Sahar; Kazemi, Amenehsadat

doi:10.1016/j.amsu.2022.103681

Cited by 2 publications

(3 citation statements)

References 12 publications

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“…As the COVID‐19 pandemic persists, many people continue to rely on antiviral treatments, such as RDV. Even though RDV is not generally recommended for pregnant people due to a lack of clinical trial data, it has been administered during pregnancy on a compassionate use basis (Budi et al, 2022 ; Burwick et al, 2021 ; Gutierrez et al, 2022 ; Jorgensen, Davis, & Lapinsky, 2021 ; Lampejo, 2021 ; Marzban‐Rad et al, 2022 ; Saroyo et al, 2021 ). There are registries to monitor pregnancy outcomes in individuals exposed to RDV (FDA, 2022 ; UKTIS, 2022 ), which are likely to provide crucial data for epidemiologic studies.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the safety of RDV, hepatotoxicity and nephrotoxicity have been implicated in human studies (Gérard et al, 2021 ; Satsangi, Gupta, & Kodan, 2021 ). However, the developmental toxicity of RDV, namely the adverse impact on embryos, is still unclear (Budi et al, 2022 ; Gutierrez et al, 2022 ; Marzban‐Rad, Ghafarzadeh, Bahmani, & Kazemi, 2022 ; Saroyo, Rumondang, Febriana, Harzif, & Irwinda, 2021 ). Due to the ongoing COVID‐19 pandemic, many people, including those who are pregnant or may become pregnant, will continue to be affected.…”

Section: Introductionmentioning

confidence: 99%

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Developmental toxicity of remdesivir, an anti‐COVID‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Kirkwood-Johnson

Marikawa

2022

Birth Defects Research

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Background Remdesivir is an antiviral drug approved for the treatment of COVID‐19, whose developmental toxicity remains unclear. More information about the safety of remdesivir is urgently needed for people of childbearing potential, who are affected by the ongoing pandemic. Morphogenetic embryoid bodies (MEBs) are three‐dimensional (3D) aggregates of pluripotent stem cells that recapitulate embryonic body patterning in vitro, and have been used as effective embryo models to detect the developmental toxicity of chemical exposures specifically and sensitively. Methods MEBs were generated from mouse P19C5 and human H9 pluripotent stem cells, and used to examine the effects of remdesivir. The morphological effects were assessed by analyzing the morphometric parameters of MEBs after exposure to varying concentrations of remdesivir. The molecular impact of remdesivir was evaluated by measuring the transcript levels of developmental regulator genes. Results The mouse MEB morphogenesis was impaired by remdesivir at 1–8 μM. Remdesivir affected MEBs in a manner dependent on metabolic conversion, and its potency was higher than GS‐441524 and GS‐621763, presumptive anti‐COVID‐19 drugs that act similarly to remdesivir. The expressions of developmental regulator genes, particularly those involved in axial and somite patterning, were dysregulated by remdesivir. The early stage of MEB development was more vulnerable to remdesivir exposure than the later stage. The morphogenesis and gene expression profiles of human MEBs were also impaired by remdesivir at 1–8 μM. Conclusions Remdesivir impaired mouse and human MEBs at concentrations that are comparable to the therapeutic plasma levels in humans, urging further investigation into the potential impact of remdesivir on developing embryos.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Developmental toxicity of remdesivir, an anti‐COVID‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Kirkwood-Johnson

Marikawa

2022

Birth Defects Research

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“…However, pregnant women were not included in this report. Several reviews reported the use of Rmd in pregnant women, 4–7 but did not analyse Rmd or GS concentration neither in mothers nor in cord blood. A physiological based PK model has been done to predict mother concentrations but without fetal concentrations 8 .…”

Section: Introductionmentioning

confidence: 99%