Infections in Pregnancy With COVID-19 and Other Respiratory RNA Virus Diseases Are Rarely, If Ever, Transmitted to the Fetus: Experiences With Coronaviruses, Parainfluenza, Metapneumovirus Respiratory Syncytial Virus, and Influenza

Schwartz, David A.; Dhaliwal, Amareen

doi:10.5858/arpa.2020-0211-sa

Cited by 91 publications

(114 citation statements)

References 91 publications

(136 reference statements)

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“…Although there have been many reports of infants born to mothers tested to be SARS-CoV-2 positive [3,7,[26][27][28][29], there are only rare case reports of probable vertical transmission [4,5,9,10,30,31]. This suggests that SARS-CoV-2 either rarely infects the placenta or is prevented from transmission despite placental infection.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers

et al. 2020

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Congenital infection of SARS-CoV-2 appears to be exceptionally rare despite many cases of COVID-19 during pregnancy. Robust proof of placental infection requires demonstration of viral localization within placental tissue. Only two of the few cases of possible vertical transmission have demonstrated placental infection. None have shown placental expression of the ACE2 or TMPRSS2 protein, both required for viral infection. We examined 19 COVID-19 exposed placentas for histopathologic findings, and for expression of ACE2, and TMPRSS2 by immunohistochemistry. Direct placental SARS-CoV-2 expression was studied by two methods-nucleocapsid protein expression by immunohistochemistry, and RNA expression by in situ hybridization. ACE2 membranous expression in the syncytiotrophoblast (ST) of the chorionic villi is predominantly in a polarized pattern with expression highest on the stromal side of the ST. In addition, cytotrophoblast and extravillous trophoblast express ACE2. No ACE2 expression was detected in villous stroma, Hofbauer cells, or endothelial cells. TMPRSS2 expression was only present weakly in the villous endothelium and rarely in the ST. In 2 of 19 cases, SARS-CoV-2 RNA was present in the placenta focally in the ST and cytotrophoblast. There was no characteristic histopathology present in our cases including the two placental infections. We found that the placenta is capable of being infected but that this event is rare. We propose one explanation could be the polarized expression of ACE2 away from the maternal blood and pronounced paucity of TMPRSS2 expression in trophoblast.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers

et al. 2020

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“…Clinical disease in the large majority of these mothers was non-existent or mild [1,6], with only rare instances of significant maternal complications. Similar to such previous coronavirus diseases as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) [7], and other RNA respiratory viruses [8], there was no definitive mother-to-infant (vertical) transmission recognized at that time [8,9]. However, following the subsequent progression of the pandemic to involve countries in the Western Hemisphere, Europe, and the Middle East, the spectrum of reported clinical manifestations of the infection in pregnancy appeared to worsen, with pregnant women developing severe and critical pneumonia, thrombosis, cardiomyopathy, multiorgan disease, need for intensive care, and mechanical ventilation which, in a small number of cases, resulted in maternal deaths [10][11][12][13].…”

Section: Introductionmentioning

confidence: 94%

Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2

Schwartz

Morotti

2020

Viruses

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127

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The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.

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“…Perinatal SARS-CoV-2 infection and vertical transmission is also hypothesized (Chen et al, 2020a;Zeng et al, 2020a). An early-onset neonatal infection with elevated IgM antibody to the virus could not confirm intrauterine vertical transmission of SARS-CoV-2 (Schwartz & Schwartz, 2020). In a COVID-19 infected neonate case report showed positive RT-PCR assay 36 hours after birth, but had negative cord blood and placenta.…”

Section: Introductionmentioning

confidence: 93%

Adverse outcomes in SAR-CoV-2 (COVID-19) and SARS virus related pregnancies with probable vertical transmission

Bahadur¹,

Homburg²,

Yoong³

et al. 2020

JBRA

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The global severe acute respiratory syndrome-related coronavirus SARS-CoV-2 (COVID-19) pandemic has had an unprecedented impact on all aspects of daily life and healthcare. Information on the infection risks for pregnant women and their offspring have so far been limited to small case series, until a large UK report on 427 SARS-CoV-2 infected pregnant women was published. Previous SARS epidemic experiences were drawn upon. Diagnostic use of real time polymerase chain reaction (RT-PCR) and IgG and IgM antibody tests are fraught with concerns of non-validation and false negative results, as are sampling methodologies. Virtually no information on controls accompany these reports. Infection of the mother and baby has serious implications for obstetric and neonatal care. Information on early and late stage pregnancy infection and the relationship to severity of infection on fetal development is both useful and clearly warranted. An increasing number of reports centre around mildly infected women showing no evidence of fetal infection while a few reports suggesting vertical transmission require further validation. Vertical transmission from mother to baby however small would have profound health implications for obstetric and neonatal care and fetal abnormalities. Some data suggesting intrapartum vertical transmission from mother to baby cannot be dismissed given the lack of controls and limitations of diagnostic viral tests. This analysis covers some key early reports addressing pregnancy outcomes following SARS-CoV-2 infection.

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Infections in Pregnancy With COVID-19 and Other Respiratory RNA Virus Diseases Are Rarely, If Ever, Transmitted to the Fetus: Experiences With Coronaviruses, Parainfluenza, Metapneumovirus Respiratory Syncytial Virus, and Influenza

Cited by 91 publications

References 91 publications

SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers

SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers

Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2

Adverse outcomes in SAR-CoV-2 (COVID-19) and SARS virus related pregnancies with probable vertical transmission

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