Baud et al and Hosier et al’s studies describe two women suffering an adverse outcome during their pregnancy, notably miscarriage and severe preeclampsia respectively [17, 15]. The miscarriage occurred in a symptomatic 28 year old woman at 19 weeks gestation. Baud et al concluded that the miscarriage appeared to be related to placental infection with SARS-CoV-2 which demonstrated mixed inflammatory infiltrates composed of neutrophils and monocytes on histological examination. Contamination during delivery was deemed unlikely given that all swabs from the foetus including the axillae, meconium, mouth and fetal blood were negative [17].
Wong et al reported a 57% miscarriage rate in a study of 12 pregnant women conducted during the 2002 SARS epidemic. They attributed this to acute or chronic placental insufficiency caused by severe maternal respiratory failure and hypoxemia thereby reducing uterine placental flow [20].
Hosier et al’s study showed a 35 year old COVID-19 positive woman who presented at 22 weeks gestation with severe preeclampsia. This patient chose to terminate her pregnancy due to her heightened risk of maternal morbidity and mortality. High levels of SARS-CoV-2 were identified in the placenta and the invasion of intervillous macrophages was also seen on histology. Hosier et al concluded that COVID-19 may have contributed to placental inflammation resulting in early-onset preeclampsia and worsening maternal disease. It is important to note, however, that this patient was previously diagnosed with gestational hypertension which is a risk factor for her later developing preeclampsia in this pregnancy. No definitive evidence for fetal infection was described [15].
Shanes et al examined 16 placentas in COVID-19 positive women. The placentas showed features of maternal vascular malperfusion, most prominently decidual arteriopathy and increased incidence of chorangiosis. Although, placental swabs were not performed which makes it unclear whether it was a local phenomenon or a systemic phenomenon [5]. Similarly, Hosier et al showed similar risk factors for maternal vascular malperfusion, i.e. gestational hypertension and preeclampsia [15]. This may tentatively imply a link between COVID-19 and severe preeclampsia.
Mulvey et al analysed five COVID-19 positive mothers’ placentas and concluded a thrombotic fetal vascular malformation phenomenon along with probable placental thrombosis lead to placental insufficiency. All five newborns were successfully delivered which may be attributed to the mothers developing COVID-19 closer to full term. Mulvey et al hypothesize that infection earlier in the gestational course may have more serious consequences such as placental insufficiency with associated miscarriages or low birth weight infants [22]. This may be why the two adverse outcomes in our study described by Hosier et al and Baud et al occurred during the second trimester.
Of the 11 studies we analysed for our literature review, Patanè et al’s is the only study which supports the possibility of vertical transmission in utero on the basis of their finding of positive SARS-CoV-2 infection in the maternal, neonatal and placental tissue. One neonate tested positive at birth, 24 hours and on day 7 and the other only tested positive on day 7. Both of these women’s placentas exhibited signs of chronic intervillositis accompanied by the presence of macrophages in the villous and intervillous space [14].
Dong et al showed elevated IgM antibody levels 2 hours after birth in a neonate born to a mother with COVID-19 suggesting that vertical transmission is possible, even if it is uncommon. This neonate also had elevated cytokines and a leucocytosis. IgM antibodies do not cross the placenta and normally appear 3 to 7 days after infection suggesting the infection occurred in utero. Confusingly, this infant repeatedly tested negative for SARS-CoV-2 on the nasopharyngeal swabs [23]. It is important to consider the accuracy of nasopharyngeal and oral swab RT-PCR assays for SARS-CoV-2 which is deemed to have a sensitivity of between 56% and 83% [24].
The major limitation of our study is the small sample size of only 45 COVID-19 positive pregnant women and thus we cannot conclusively rule out the possibility of vertical transmission, though we deem it unlikely. However, we can consider that COVID-19 may affect the placental tissue due to the detection of the virus in certain cases.