Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology

Abstract

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.

The Immunological Role of the Placenta in SARS-CoV-2 Infection—Viral Transmission, Immune Regulation, and Lactoferrin Activity

“…Moreover, further research and observations of pregnant women and their children with the virus are needed to assess further long-lasting clinical implications which can appear in offspring. Furthermore, more assessment should be made regarding the rates of vertical transmission in the early trimester of pregnancy and the potential risk for consequent fetal morbidity and mortality [ 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 148 , 149 , 150 , 151 ]. To date, research is underway to check whether the SARS-CoV-2 virus can be transmitted from mother to fetus.…”

SARS-CoV-2-associated cytokine storm during pregnancy as a possible risk factor for neuropsychiatric disorder development in post-pandemic infants

“…A small cohort study performed in women infected during late pregnancy found that known risk factors for COVID-19 severity in the general population, such as obesity, increased the need of a premature C-section to alleviate respiratory difficulty ( Lokken et al, 2020 ). Fetal growth restrictions ( Sukhikh et al, 2021 ), low birth weight of at-term babies ( Patanè et al, 2020 ) and occasional miscarriages and stillbirths have also been reported following COVID-19 diagnosis in pregnant patients ( Baud et al, 2020 ; Sukhikh et al, 2021 ). However, in other cohorts no increased risk of premature delivery or impaired fetal growth were described ( Santana and Luis, 2021 ).…”

“…Recent reports have shown that the two known receptors for SARS-CoV-2, angiotensin-converting enzyme (ACE2) and transmembrane protease serine 2, are widely expressed in the placenta and in the maternal-fetal interface (M. Li et al, 2020 ), suggesting that, as with any respiratory virus, mother-to-child transmission of SARS-CoV-2 could occur. Accordingly, some case studies have demonstrated the presence of SARS-CoV-2 genome in placentas from women infected during the second and third trimester of pregnancy ( Hosier et al, 2020 ; Patanè et al, 2020 ; Sukhikh et al, 2021 ), with increased placental infiltration of inflammatory cells, mostly phagocytic cells ( Kirtsman et al, 2020 ; Schoenmakers et al, 2020 ). In one of these cases, an uneventful and healthy pregnancy was complicated immediately after the patient acquired COVID-19 at 21 weeks of pregnancy.…”

“…In one of these cases, an uneventful and healthy pregnancy was complicated immediately after the patient acquired COVID-19 at 21 weeks of pregnancy. Combined analysis of placental tissue, umbilical cord blood and child blood indicated the occurrence of vertical viral transmission, possibly causing maternal vascular malperfusion, which led to premature birth (26th week) and child death ( Sukhikh et al, 2021 ). In another study, viral genome has been detected not only in some of the analyzed at-term placentas but also in umbilical cords as well as in vaginal mucosa and milk specimens ( Fenizia et al, 2020 ).…”

“…Despite initial studies suggested that COVID-19 is associated with low birth-weight infants and increased risk of preterm deliveries ( Lokken, Huebner, et al, 2021 ; Lokken, Taylor, et al, 2021 ; Zambrano et al, 2020 ), whether SARS-CoV-2 infection has the potential to negatively affect intrauterine development remains controversial. Several studies suggest that mother-to-child transmission of SARS-CoV-2 can occur in utero, intrapartum, or early in the postnatal period ( Fenizia et al, 2020 ; Hosier et al, 2020 ; Patanè et al, 2020 ; Sukhikh et al, 2021 ). Although most neonates testing positive for the virus do not develop severe respiratory symptoms ( Raschetti et al, 2020 ), studies addressing the consequences of this infection to the developing brain are lacking.…”