Maternal-fetal vertical SARS-CoV2 transmission cannot be dismissed
Gulam Bahadur considered vertical transmission of COVID-19 in a systematic review.
Published 08 July 2020
Despite an abundance of case reports and much heterogeneity, a new systematic review of 80 publications and a total of 846 COVID-19 positive pregnant women plus 688 babies born to infected mothers suggests that vertical transmission is possible.
The much anticipated Tuesday session on COVID-19 heard Gulam Bahadur from London present details of a systematic review from his group to deduce whether maternal-fetal vertical transmission of SARS-CoV2 was plausible. The short answer was that vertical transmission is indeed possible and, hence, cannot be dismissed.
Pregnant women were considered by the WHO a vulnerable group early in the pandemic based on the fact that pregnancy alters the immune system and increases susceptibility to certain infectious diseases. As the pandemic evolved, it became apparent that pregnant women were not at any greater risk of infection, with severity of COVID19 comparable to that of the general population. One aspect, though, remained before any concerns surrounding a COVID-19 affected pregnancy would abate: is there transmission of SARS-CoV2 from the mother to the fetus? This was the research question which Bahadur’s study sought to answer by systematically reviewing 80 publications – which included a total of 846 COVID-19 positive pregnant women and 688 babies born to infected mothers.
The review found that the vast majority of the publications studied a very low number of babies (<5), who were diagnosed with tests based on detection of antibodies (IgM/IgG) or viral load (RT-PCR). Overall, only 10 babies were positive for viral load but three of them were positive for IgG/IgM antibodies, suggesting that, since IgM antibodies cannot cross the placenta, 30% of babies positive for COVID19 acquired the infection in utero. From the total number of positive amniotic fluid samples that only 20% of babies were also diagnosed as positive with RT-PCR.
Eleven studies assessed placentas but only three placentas from second and third trimesters were found infected. The pathology examination of those placentas demonstrated infiltration of inflammatory cells such as neutrophils and monocytes in the subchorial space, increased intervillous fibrin deposition, no vasculopathy and localisation of SARS-CoV-2 to syncytiotrophoblast cells.
Bahadur acknowledged the enormous heterogeneity of the included studies, arising from variations in sampling timing and methods, patient infectivity level, diagnostic tools and their sensitivity and specificity, and the lack of essential controls. Despite these limitations, he was confident that vertical transmission can be justified - and not exclusively on the basis of the reviewed case reports. Indeed, several mechanistic theories have postulated that viral transmission from the maternal to the fetal side could be accomplished via canonical (ACE2) or alternative (CD147) receptors present in the placenta to which SARS-CoV2 can bind.
A study presented by Dr Wafaa Essahib from Brussels later in the same session did show that both these receptors are additionally expressed in human oocytes and blastocysts, suggesting a new possible route for SARS-CoV-2 detection in the fetus. However, this would mainly concern a future or a very early pregnancy of a COVID-19 infected woman. It is thus important to take into account the latest literature suggesting that SARS-CoV2 receptors are not expressed in the chorioamniotic membranes in the third trimester, emphasising that the exact mechanisms and cellular receptors that SARS-CoV2 exploits to penetrate the fetal compartment in the later gestational weeks are still unclear.
When asked by the audience to provide an estimate for vertical transmission, Bahadur responded that these are ‘early days’ where estimates cannot be based on case reports in the absence of specific country-wise real-world data of pregnant women with COVID-19. Addressing another question regarding the implications of vertical transmission for the fetus, he stated that the main concern was miscarriage resulting from oxygen deprivation to the fetus.