Placenta and SARS-CoV-2: the state-of-the-art – Part. 4
| 09 June 2022
During this four-chapter journey, we tried to trace the different points that led to untangling, at least in part, the complex universe of placental SARS-CoV-2 infection. Here, we trace and explain what we know for sure and certainly not about this topic. We will address questions such as “are pregnant women more susceptible to infection by SARS-CoV-2?”, “What and how much do we know about the transmission of SARS-CoV-2 to the newborn from an infected mother?” and many others.
Are pregnant women more susceptible to infection by SARS-CoV-2?
At the moment, we have no incontrovertible evidence that can allow us to conclude that pregnancy constitutes a clear risk factor for increasing susceptibility to the virus. In fact, various studies have tried to address this question and the results have proved quite different and, at times, contradictory.
For example, in a report by the US Centers for Disease Control and Prevention (CDC) , the number of laboratory-confirmed cases of SARS-CoV-2 infection was higher than expected among pregnant people; among women of reproductive age infected with SARS-CoV-2, 9% were pregnant compared with an estimated 5% of women aged 15 to 44 who are pregnant at any time.
However, there were large amounts of missing data. Investigators were unable to adjust to potentially different testing and assessment rates given the more prevalent screening of asymptomatic pregnant people.
Similarly, a Washington state study  reported higher infection rates among pregnant patients (13.9 per 1000 deliveries) than non-pregnant adults aged 20 to 39 years (7.3 per 1000 people); this study was also unable to account for differential test rates in pregnant versus non-pregnant people.
Is a pregnant woman who becomes infected at greater risk of serious illness?
Yes, there is quite clear evidence that a pregnant woman who becomes ill with SARS-CoV-2 may have a more severe disease. For example, some of the best data comes from the CDC's COVID-19 surveillance system, which included more than 400,000 people of reproductive age with symptomatic COVID-19 and adjusted for age, race and ethnicity, and underlying medical conditions.
Compared to non-pregnant women, pregnant people were 3 times more likely to be admitted to an intensive care unit (ICU) (10.5 vs 3.9 per 1000), 2.9 times more likely to require ventilation invasive (2.9 vs 1.1 per 1000 cases), 2.4 times more likely to require extracorporeal membrane oxygenation (0.7 vs 0.3 per 1000 cases), and 1.7 times more likely to die .
Further studies in the United States and Europe report similar results. For example, a study conducted by 4 European hospitals  compared pregnant and non-pregnant women matching the propensity score for age, body mass index and comorbidity and found an increased risk of serious illness during pregnancy, including an increased risk of ICU admission (primary outcome).
The study also found an increased risk of hospitalization, the need for oxygen therapy, and the need for endotracheal intubation (secondary outcomes) in infected pregnant women . A Washington state study found an increased risk of hospitalization and a higher mortality rate among pregnant people compared to non-pregnant people of a similar age .
The increased risk of disease severity in pregnancy may be due to mechanical changes such as decreased lung volume as the fetus grows, immunological changes, and an increased risk of thromboembolic disease.
What and how much do we know about the transmission of SARS-CoV-2 to the newborn from an infected mother?
Transmission of SARS-CoV-2 to the child appears to be a very rare event . This could be explained by two types of reasons: a low viral load (viremia) and a low expression of target receptors for virion entry such as ACE2 and TMPRSS2 [7-8].
In terms of adverse pregnancy outcomes, do we have evidence of any particular outcome?
Yes, a recent systematic review and meta-analysis of relatively high-quality studies with appropriate comparison groups found an increased risk of preeclampsia, preterm birth and stillbirth among pregnant people infected with SARS-CoV-2 compared to those without SARS-CoV-2 infection.
Among pregnant people with COVID-19, severe disease has been associated with preeclampsia, preterm birth, gestational diabetes, and low birth weight compared to those with mild disease . Two studies published after the meta-analysis found similar results.
A multinational cohort study found that pregnant people with COVID-19 were at greater risk for preeclampsia / eclampsia and preterm birth than pregnancies without COVID-19. In an observational study of 1219 pregnant patients who tested positive for SARS-CoV-2, those with severe disease had increased cesarean delivery, hypertensive disorders of pregnancy, and preterm delivery compared to asymptomatic patients.
- Ellington S., Strid P., Tong V.T., et al. Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–June 7, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:769–775.
- Lokken E.M., Taylor G.G., Huebner E.M., et al. Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients. Am J Obstet Gynecol. 2021;225:75.e1–75.e16.
- Zambrano L.D., Ellington S., Strid P., et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1641–1647.
- Badr D.A., Mattern J., Carlin A., et al. Are clinical outcomes worse for pregnant women at ≥20 weeks’ gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching. Am J Obstet Gynecol. 2020;223:764–768.
- Lokken E.M., Huebner E.M., Taylor G.G., et al. Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State. Am J Obstet Gynecol. 2021;225:77.e1–77.e14.
- World Health Organization Definition and categorization of the timing of mother-to-child transmission of SARS-CoV-2 scientific brief, 8 February 2021. 2021. https://apps.who.int/iris/handle/10665/339422
- Edlow A.G., Li J.Z., Collier A.Y., et al. Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer, and placental pathology in pregnancies during the COVID-19 pandemic. JAMA Netw Open. 2020;3
- Ouyang Y., Bagalkot T., Fitzgerald W., et al. Term human placental trophoblasts express SARS-CoV-2 entry factors ACE2, TMPRSS2, and Furin. mSphere. 2021;6 e00250-21.
- Wei S.Q., Bilodeau-Bertrand M., Liu S., Auger N. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. CMAJ. 2021;193:E540–E548.