Functional consequences of SARS-CoV-2 infection in pregnant women, fetoplacental unit, and neonate

Abstract

The SARS-CoV-2 infection causes COVID-19 disease, characterized by acute respiratory distress syndrome, bilateral pneumonia, and organ failure. The consequences of maternal SARS-CoV-2 infection for the pregnant woman, fetus, and neonate are controversial. Thus, it is required to determine whether there is viral and non-viral vertical transmission in COVID-19. The disease caused by SARS-CoV-2 leads to functional alterations in asymptomatic and symptomatic pregnant women, the fetoplacental unit and the neonate. Several diseases of pregnancy, including COVID-19, affect the fetoplacental function, which causes in utero programming for young and adult diseases. A generalized inflammatory state and a higher risk of infection are seen in pregnant women with COVID-19. Obesity, diabetes mellitus, and hypertension may increase the vulnerability of pregnant women to infection by SARS-CoV-2. Alpha, Delta, and Omicron variants of SARS-CoV-2 show specific mutations that seem to increase the capacity of the virus to infect the pregnant woman, likely due to increasing its interaction via the virus S protein and angiotensin-converting enzyme 2 receptors. This review shows the literature addressing to what extent COVID-19 in pregnancy affects the pregnant woman, fetoplacental unit, and neonate. Prospective studies that are key in managing SARS-CoV-2 infection in pregnancy are discussed.

Keywords: Covid-19; Fetus; Neonate; Placenta; Pregnancy; Virus.

Fig. 1

Symptoms in patients with COVID-19. The distribution of most frequent symptoms in reports of patients with coronavirus disease 2019 (COVID-19) in case surveillance and in-hospital patients with fever and cough are predominant, with few cases of gastrointestinal complications. Circles show the mean values reported in , , , .

Fig. 2

Complications and risk factors in patients with COVID-19. Infection with SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), which may result in generalized inflammation configuring sepsis (Sepsis), respiratory and heart failure, and thromboembolism. COVID-19 may also lead to septic shock associated with low blood pressure, pale and cold arms and legs, chills, difficulty breathing, and decreased urine output. Risk factors for COVID-19 include chronic diseases (hypertension, diabetes mellitus, obesity), body mass index (BMI) >35 kg/m², male gender and age > 65 years. From data in , , , .

Fig. 3

SARS-CoV-2 variants and effects in pregnant women. SARS-CoV-2 infection of pregnant women may result from exposure to the Alpha, Delta, or Omicron variants. Mutations in these variants lead to several alterations in maternal health, including complications in future pregnancies and a higher incidence of diseases during pregnancy. These alterations are associated with various laboratory parameters in patients with mild or severe infections. Gene mutations result in modifications of the mechanisms by which the virus enters the target cells by predominantly modifying the S1/S2 regions of the S protein of the virus leading to higher cleavage of this protein S1/S2 region by furin. These alterations increase virus binding to their membrane receptor angiotensin-converting enzyme 2 (ACE2). Alternatively, some mutations may increase the virus immune evasion or affect predominantly young patients. Mutations: N501Y, asparagine by tyrosine at position 501; P681H, proline by histidine at position 681; D614G, aspartic acid by glycine at position 614; L452R, leucine by arginine at position 452; T478K, threonine by lysine at position 478. CRP, C reactive protein; GDM, gestational diabetes mellitus; SGA, small for gestational age; Th, helper T cells. Solid red arrows show an increase. Information is taken from references quoted in the body text. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Reported alterations in the placenta, fetus, and neonate/infant in pregnancies with coronavirus disease 2019. The human placenta (Placenta) in pregnancies where the mother was positive for SARS-CoV-2 show several alterations, including increased inflammation and reduced vascular perfusion, expression of antioxidant enzymes, and mitochondrial respiration. Several alterations are also described in the growing fetus (Fetus), including restricted growth, cardiac alterations, and reduced fetal movements. Pregnancies with SARS-CoV-2 infection are associated with prematurity and increased admission to the intensive care unit after birth (Neonate and infant). IUGR, intrauterine growth restriction; IgM, immunoglobulin M; IgG, immunoglobulin G; PCR, polymerase chain reaction; PROM, premature rupture of membranes; NICU, neonatal intensive care unit; STB, syncytiotrophoblast; vWf, von Willebrand factor. Information is taken from references quoted in the body text.

Fig. 5

Proposed SARS-CoV-2 infection cycle in the generation of women from COVID-19 pregnancies. Pregnancy is a physiological condition where the mother can get infected with SARS-CoV-2 developing coronavirus disease 2019 (COVID-19). The intrauterine and perinatal environments are stages in life where the programming of human diseases may happen, and this may get worse when the neonate comes from a mother with COVID-19. The exposure of the mother to breastfeeding, neonate, children, and adults (women and men) from COVID-9 mothers may determine high susceptibility to developing young and adult diseases. The latter is triggered by ecto-exposome factors that are part of the environmental contaminants, mainly in the form of contaminated food, air, and water. Unhealthy conditions such as obesity, diabetes mellitus, and hypertension will increase the risk of infection in pregnancy. However, the cell and molecular mechanisms accounting for SARS-CoV-2 infection in the COVID-19 pregnancies generation of women of reproductive age are not yet available.