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Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.
JAMA Netw Open. 2020 12 01; 3(12):e2030455.JN

Abstract

Importance

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.

Objective

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.

Exposures

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.

Results

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.

Authors+Show Affiliations

Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Obstetrics, Gynecology and Reproductive Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts. Department of Microbiology, Harvard Medical School, Boston, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston.Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston.Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston.Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, Massachusetts.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33351086

Citation

Edlow, Andrea G., et al. "Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic." JAMA Network Open, vol. 3, no. 12, 2020, pp. e2030455.
Edlow AG, Li JZ, Collier AY, et al. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020;3(12):e2030455.
Edlow, A. G., Li, J. Z., Collier, A. Y., Atyeo, C., James, K. E., Boatin, A. A., Gray, K. J., Bordt, E. A., Shook, L. L., Yonker, L. M., Fasano, A., Diouf, K., Croul, N., Devane, S., Yockey, L. J., Lima, R., Shui, J., Matute, J. D., Lerou, P. H., ... Alter, G. (2020). Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Network Open, 3(12), e2030455. https://doi.org/10.1001/jamanetworkopen.2020.30455
Edlow AG, et al. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020 12 1;3(12):e2030455. PubMed PMID: 33351086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. AU - Edlow,Andrea G, AU - Li,Jonathan Z, AU - Collier,Ai-Ris Y, AU - Atyeo,Caroline, AU - James,Kaitlyn E, AU - Boatin,Adeline A, AU - Gray,Kathryn J, AU - Bordt,Evan A, AU - Shook,Lydia L, AU - Yonker,Lael M, AU - Fasano,Alessio, AU - Diouf,Khady, AU - Croul,Natalie, AU - Devane,Samantha, AU - Yockey,Laura J, AU - Lima,Rosiane, AU - Shui,Jessica, AU - Matute,Juan D, AU - Lerou,Paul H, AU - Akinwunmi,Babatunde O, AU - Schmidt,Aaron, AU - Feldman,Jared, AU - Hauser,Blake M, AU - Caradonna,Timothy M, AU - De la Flor,Denis, AU - D'Avino,Paolo, AU - Regan,James, AU - Corry,Heather, AU - Coxen,Kendyll, AU - Fajnzylber,Jesse, AU - Pepin,David, AU - Seaman,Michael S, AU - Barouch,Dan H, AU - Walker,Bruce D, AU - Yu,Xu G, AU - Kaimal,Anjali J, AU - Roberts,Drucilla J, AU - Alter,Galit, Y1 - 2020/12/01/ PY - 2020/12/22/entrez PY - 2020/12/23/pubmed PY - 2021/1/15/medline SP - e2030455 EP - e2030455 JF - JAMA network open JO - JAMA Netw Open VL - 3 IS - 12 N2 - Importance: 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. Objective: 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. Exposures: 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. Results: 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. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/33351086/Assessment_of_Maternal_and_Neonatal_SARS_CoV_2_Viral_Load_Transplacental_Antibody_Transfer_and_Placental_Pathology_in_Pregnancies_During_the_COVID_19_Pandemic_ L2 - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.30455 DB - PRIME DP - Unbound Medicine ER -