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What key biological characteristics of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and placental function and pathology have implications for vertical transmission and neonatal protection?
In this prospective cohort study including 127 pregnancies, there was no maternal viremia, placental infection, or vertical transmission of SARS-CoV-2. Compromised transplacental transfer of anti–SARS-CoV-2 antibodies with robust transfer of influenza-specific immunity and nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 were noted.
These findings suggest that, although low rates of maternal viremia and patterns of placental SARS-CoV-2 receptor distribution may underlie the rarity of vertical transmission, reduced transplacental transfer of anti–SARS-CoV-2 antibodies may leave neonates at risk for infection.
Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti–SARS-CoV-2 antibody, and incidence of fetoplacental infection.
Design, Setting, and Participants
This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription–polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2.
SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR.
Main Outcomes and Measures
The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti–SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta.
Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti–receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti–SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti–receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted.
Conclusions and Relevance
In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.
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Accepted for Publication: October 28, 2020.
Published: December 22, 2020. doi:10.1001/jamanetworkopen.2020.30455
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Edlow AG et al. JAMA Network Open.
Corresponding Author: Andrea G. Edlow, MD, MSc, Vincent Center for Reproductive Biology, Massachusetts General Hospital, 55 Fruit St, Thier Research Building, 903B, Boston, MA 02114 (email@example.com).
Author Contributions: Dr Edlow had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kaimal, Roberts, and Alter contributed equally to the work.
Concept and design: Edlow, Li, Collier, Boatin, Gray, Fasano, Devane, Matute, Lerou, Schmidt, Corry, Kaimal, Roberts, Alter.
Acquisition, analysis, or interpretation of data: Edlow, Li, Collier, Atyeo, James, Boatin, Bordt, Shook, Yonker, Fasano, Diouf, Croul, Devane, Yockey, Lima, Shui, Matute, Akinwunmi, Feldman, Hauser, Caradonna, De la Flor, D'Avino, Regan, Corry, Coxen, Fajnzylber, Pepin, Barouch, Seaman, Walker, Yu, Kaimal, Roberts, Alter.
Drafting of the manuscript: Edlow, Li, James, Devane, Akinwunmi, Pepin, Roberts, Alter.
Critical revision of the manuscript for important intellectual content: Edlow, Li, Collier, Atyeo, James, Boatin, Gray, Bordt, Shook, Yonker, Fasano, Diouf, Croul, Devane, Yockey, Lima, Shui, Matute, Lerou, Schmidt, Feldman, Hauser, Caradonna, De la Flor, D'Avino, Regan, Corry, Coxen, Fajnzylber, Pepin, Barouch, Seaman, Walker, Yu, Kaimal, Roberts, Alter.
Statistical analysis: Edlow, Collier, Atyeo, James, Bordt, De la Flor, Pepin, Alter.
Obtained funding: Edlow, Li, Yonker, Fasano, Schmidt, Yu, Kaimal, Alter.
Administrative, technical, or material support: Edlow, Li, Collier, Boatin, Gray, Shook, Yonker, Fasano, Diouf, Croul, Devane, Yockey, Lima, Matute, Lerou, Akinwunmi, Feldman, Hauser, Caradonna, D'Avino, Coxen, Pepin, Barouch, Seaman, Yu, Kaimal, Roberts, Alter.
Supervision: Edlow, Collier, Gray, Lerou, De la Flor, Pepin, Barouch, Walker, Kaimal, Alter.
Conflict of Interest Disclosures: Dr Li reported serving as a consultant for Abbvie and Jan Biotech. Dr Boatin reported serving as a consultant for Microchips Biotech and as a scientific advisory board member for Reproductive Health Investors Alliance. Dr Gray reported receiving nonfinancial support from Illumina, and personal fees from Quest Diagnostics, BillionToOne, and Aetion outside the submitted work. Dr Fasano reported serving as a cofounder of and owning stock in Alba Therapeutics and serving on scientific advisory boards for NextCure and Viome outside the submitted work. Dr Schmidt reported receiving grants from the Bill and Melinda Gates Foundation, Defense Advanced Research Projects Agency (DARPA), Henry Jackson Foundation, amfAR, Ragon Institute, Massachusetts Consortium on Pathogen Readiness, Janssen, Gilead, Legend, Sanofi, Zentalis, Alkermes, and Intima; personal fees from SQZ Biotech; and having a patent for a SARS-CoV-2 vaccine licensed to Janssen. Dr Pepin reported owning stock in Gilead Sciences, BioNano Genomics, Biogen, Bluebird Bio, ImmunoGen, Pfizer, and Bristol-Myers Squibb. Dr Kaimal reported receiving grants from the National Institutes of Health outside the submitted work. Dr Roberts reported receiving author royalties from UpToDate and Cambridge University Press outside the submitted work. Dr Alter reported serving as a founder of Systems Seromyx. No other disclosures were reported.
Funding/Support: This work was supported by the National Institutes of Health, including NICHD (grants R01HD100022 and 3R01HD100022-02S2 [Dr Edlow], K12HD000849 [Dr Collier], and K23HD097300 [Dr Boatin]); National Heart, Lung, and Blood Institute (grants K08 HL146963 [Dr Gray] and K08 HL143183 [Dr Yonker]); and National Institute of Allergy and Infectious Diseases (grant No. R01 AI146779 [Dr Schmidt]). Support was also provided by the Cystic Fibrosis Foundation (grant No. YONKER18Q0 [Dr Yonker]), a gift from Mark, Lisa, and Enid Schwartz (Dr Li), and by the MGH Department of Pathology Vickery-Colvin award. Additional support was provided by the Ragon Institute of MGH and MIT, Massachusetts General Hospital Department of Obstetrics and Gynecology, Massachusetts Consortium on Pathogen Readiness, the Evergrande Fund, the Bill and Melinda Gates Foundation (grant No. 235730), and the Harvard Center for AIDS Research (grant No. P30 AI060354-11).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Dana Cvrk, CNM, Muriel Schwinn, NP, Robin Azevedo, RN, Laurel Gardner, RN, Suzanne Stanton, RN, Ricardo Aguayo, BS, Annika Gompers, MPhil, Alec Brown, BA, and Laurie P. Foster, RN, provided critical assistance with participant recruitment. Nancy Zimmerman, BA, Mark Schwartz, BA, MBA, Lisa Schwartz, BA, MBA, Terry Ragon, BA, and Susan Ragon, BA, and Jeffrey Ecker, MD, provided early material support. Bing Chen, PhD, assisted with protein production. Marie-Charlotte Meinsohn, PhD, Ngoc Minh Phuong Nguyen, PhD, and Maeva Chauvin, PhD, assisted with the SARS-CoV-2 placental in situ hybridization. Noe B. Mercado, BS, and Catherine Jacob-Dolan, BS, assisted with viral load assays. Ms Azevedo, Gardner, and Stanton received compensation for time worked on the study.
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