Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.
Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.
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DOI：
10.1001/jamanetworkopen.2020.30455
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发表时间：
2020-12-01
影响因子：
13.8
通讯作者：
Alter G
中科院分区：
文献类型：
--
作者：
Edlow AG;Li JZ;Collier AY;Atyeo C;James KE;Boatin AA;Gray KJ;Bordt EA;Shook LL;Yonker LM;Fasano A;Diouf K;Croul N;Devane S;Yockey LJ;Lima R;Shui J;Matute JD;Lerou PH;Akinwunmi BO;Schmidt A;Feldman J;Hauser BM;Caradonna TM;De la Flor D;D'Avino P;Regan J;Corry H;Coxen K;Fajnzylber J;Pepin D;Seaman MS;Barouch DH;Walker BD;Yu XG;Kaimal AJ;Roberts DJ;Alter G
母亲严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的哪些关键生物学特征以及胎盘功能和病理学对垂直传播和新生儿保护有影响？在这项包括127例妊娠的前瞻性队列研究中，没有母体病毒血症、胎盘感染或SARS-CoV-2垂直传播。注意到抗SARS-CoV-2抗体的经胎盘转移受损，流感特异性免疫的转移稳健，SARS-CoV-2受体血管紧张素转换酶2和跨膜丝氨酸蛋白酶2的胎盘表达不重叠。这些研究结果表明，尽管母体病毒血症的低发生率和胎盘SARS-CoV-2受体分布的模式可能是垂直传播罕见的基础，但抗SARS-CoV-2抗体经胎盘转移的减少可能使新生儿处于感染的风险中。本队列研究检测了孕妇和新生儿严重急性呼吸综合征冠状病毒2型病毒载量、经胎盘抗体转移和胎盘病理学。缺乏关于母亲严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染的垂直传播风险和胎儿胎盘保护机制的生物学数据。定量测定母亲和新生儿体液中SARS-CoV-2病毒载量、抗SARS-CoV-2抗体的经胎盘通过情况以及胎儿胎盘感染的发生率。本队列研究在马萨诸塞州波士顿3个三级保健中心就诊的孕妇中进行。从2020年4月2日至6月13日招募了SARS-CoV-2逆转录聚合酶链反应（RT-PCR）结果阳性的女性，并随访至2020年7月10日。同期没有SARS-CoV-2感染的参与者被招募为来自SARS-CoV-2 RT-PCR结果阴性的孕妇的方便样本。妊娠期SARS-CoV-2感染，通过鼻咽拭子RT-PCR确定。主要结果是母亲血浆或呼吸道液和脐带血浆中的SARS-CoV-2病毒载量，母亲和脐带血浆中抗SARS-CoV-2抗体的定量，以及胎盘中SARS-CoV-2 RNA的存在。在纳入的127名孕妇中，64名RT-PCR结果为SARS-CoV-2阳性（平均[SD]年龄，31.6 [5.6]岁）和63名RT-PCR结果为SARS-CoV-2阴性（平均[SD]年龄，33.9 [5.4]岁）的孕妇提供了样本进行分析。在SARS-CoV-2感染的妇女中，23人（36%）无症状，22人（34%）病情轻微，7人（11%）病情中度，10人（16%）病情严重，2人（3%）病情危重。在107名妇女的病毒载量分析中，在母体或脐带血中没有检测到病毒血症，也没有垂直传播的证据。在77名新生儿中检测的SARS-CoV-2抗体在脐带血中定量，1人有可检测到的免疫球蛋白M的核衣壳。在88个检测的胎盘中，没有检测到SARS-CoV-2 RNA。在37名SARS-CoV-2感染妇女的抗体分析中，24名妇女（65%）检测到抗受体结合结构域免疫球蛋白G，26名妇女（70%）检测到抗核衣壳。抗SARS-CoV-2抗体的母婴转移显著低于抗流感血凝素A抗体的母婴转移（平均[SD]脐带与母体比率：抗受体结合域免疫球蛋白G，0.72 [0.57];抗核衣壳，0.74 [0.44];抗流感，1.44 [0.80]; P <0.001）。SARS-CoV-2受体血管紧张素转换酶2和跨膜丝氨酸蛋白酶2的胎盘表达不重叠。在这项队列研究中，没有证据表明SARS-CoV-2存在胎盘感染或明确的垂直传播。抗SARS-CoV-2抗体的经胎盘转移是无效的。胎盘血管紧张素转换酶2和跨膜丝氨酸蛋白酶2缺乏病毒血症和减少共表达和共定位可能是防止垂直传播的保护机制。
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. This cohort study examines maternal and neonatal severe acute respiratory syndrome coronavirus 2 viral load, transplacental antibody transfer, and placental pathology among pregnant women. 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. 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. 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. 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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影响因子：
3.8
作者：
Castanha, Priscila M. S.;Souza, Wayner V.;Brandao Filho, Sinval Pinto
通讯作者：
Brandao Filho, Sinval Pinto
DOI：
10.1126/science.aag3194
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
McAllister AK
影响因子：
168.9
作者：
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通讯作者：
Zhang, Yuanzhen
影响因子：
5.5
作者：
Abu Raya, Bahaa;Srugo, Isaac;Bamberger, Ellen
通讯作者：
Bamberger, Ellen
影响因子：
6.4
作者：
Castanha, Priscila M. S.;Braga, Cynthia;Marques, Ernesto T. A.
通讯作者：
Marques, Ernesto T. A.