SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review

Abstract

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has been associated with worse outcomes in several patient populations, including the elderly and those with chronic comorbidities. Data from previous pandemics and seasonal influenza suggest that pregnant women may be at increased risk for infection-associated morbidity and mortality. Physiologic changes in normal pregnancy and metabolic and vascular changes in high-risk pregnancies may affect the pathogenesis or exacerbate the clinical presentation of COVID-19. Specifically, SARS-CoV-2 enters the cell via the angiotensin-converting enzyme 2 (ACE2) receptor, which is upregulated in normal pregnancy. Upregulation of ACE2 mediates conversion of angiotensin II (vasoconstrictor) to angiotensin-(1-7) (vasodilator) and contributes to relatively low blood pressures, despite upregulation of other components of the renin-angiotensin-aldosterone system. As a result of higher ACE2 expression, pregnant women may be at elevated risk for complications from SARS-CoV-2 infection. Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering angiotensin-(1-7) levels, which can mimic/worsen the vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia. Indeed, early reports suggest that, among other adverse outcomes, preeclampsia may be more common in pregnant women with COVID-19. Medical therapy, during pregnancy and breastfeeding, relies on medications with proven safety, but safety data are often missing for medications in the early stages of clinical trials. We summarize guidelines for medical/obstetric care and outline future directions for optimization of treatment and preventive strategies for pregnant patients with COVID-19 with the understanding that relevant data are limited and rapidly changing.

Figure 1

Features and life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A, Structure of the SARS-CoV-2 viron. B, Viral entry methods and replication of SARS-CoV-2.

Figure 2

Pregnancy, coronavirus disease 2019 (COVID-19), and mechanisms of vascular damage. Upregulation of angiotensin-converting enzyme 2 (ACE2) receptor in pregnancy may increase the risk of severe acute respiratory syndrome coronavirus 2 infection. Binding of virus to ACE2 causes its downregulation and may increase angiotensin (Ang) II relative to Ang-(1-7), thus favoring vasoconstriction, which can mimic/worsen vascular dysfunction in preeclampsia.