SARS-CoV-2 in the context of past coronaviruses epidemics: Consideration for prenatal care

Since December 2019, the novel SARS-CoV-2 outbreak has resulted in millions of cases and more than 200 000 deaths worldwide. The clinical course among nonpregnant women has been described, but data about potential risks for women and their fetus remain scarce. The SARS and MERS epidemics were responsible for miscarriages, adverse fetal and neonatal outcomes, and maternal deaths. For COVID-19 infection, only nine cases of maternal death have been reported as of 22 April 2020, and pregnant women seem to develop the same clinical presentation as the general population. However, severe maternal cases, as well as prematurity, fetal distress, and stillbirth among newborns have been reported. The SARS-CoV-2 pandemic greatly impacts prenatal management and surveillance and raise the need for clear unanimous guidelines. In this narrative review, we describe the current knowledge about coronaviruses (SARS, MERS, and SARS-CoV-2) risks and consequences on pregnancies, and we summarize available current candidate therapeutic options for pregnant women. Finally, we compare current guidance proposed by The Royal College of Obstetricians and Gynaecologists, The American College of Obstetricians and Gynecologists, and the World Health Organization to give an overview of prenatal management which should be utilized until future data appear.     

Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2s

There remain unanswered questions concerning mother-to-child-transmission of SARS-CoV-2. Despite reports of neonatal COVID-19, SARS-CoV-2 has not been consistently isolated in perinatal samples, thus definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal-fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID-19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. Although real-time polymerase chain reaction of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID-19 was reported in eight studies, two of which were based on the detection of SARS-CoV-2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID-19. The paucity of placental co-expression of ACE-2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS-CoV-2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE-2 thus, tissue susceptibility may be broader than currently known. Further spatial-temporal studies are needed to determine the true potential for transplacental migration.     

Prevalence and clinical significance of anticardiolipin antibodies in pregnancies complicated by parvovirus B19 infection

Anticardiolipin antibodies were measured in 60 pregnant women with acute parvovirus B19 infection. Test results for eight (13.3 per cent) women were positive for anticardiolipin antibody. Six of these eight women became negative later, yielding a prevalence of anticardiolipin antibodies of 3.3 per cent (2/60) 6 months after acute parvovirus B19 infection. Anticardiolipin antibody positivity was not associated with an increased risk of abortion, fetal death, or maternal complications. This study suggests that there is an elevated frequency of anticardiolipin antibodies in pregnant women with acute parvovirus B19, probably representing an epiphenomenon. However, this is not associated with an adverse maternal or perinatal outcome.     

Environmental surveillance of SARS-CoV-2 RNA in wastewater systems and related environments in Wuhan: April to May of 2020

Wastewater-based epidemiology(WBE) has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community. Congruently, SARS-Co V-2, the etiologic agent of COVID-19, has been demonstrated to infect the gastrointestinal tissues, and be shed in feces. In the present study, SARS-Co V-2 RNA was concentrated from wastewater, sludge, surface water, ground water, sediment, and soil samples of municipal and hospital wastewater systems and related envi...     

污水新型冠状病毒监测研究进展及启示

新冠肺炎疫情暴发以来,全球多个国家和地区频繁在污水中检测出新型冠状病毒核酸. 开展基于污水流行病学的污水新型冠状病毒监测,可作为人群新冠肺炎监测的重要补充,获得的核酸浓度数据和序列突变分析结果,可为新冠肺炎疫情早期预警、早期发现无症状感染者、评估感染规模、监测人群流行趋势、开展病毒溯源调查、制定防控政策等提供科学依据. 鉴于此,本文系统介绍了国内外污水中新型冠状病毒的来源及影响病毒存活的主要因素,归纳了常用的污水新型冠状病毒富集浓缩和核酸检测方法,概括了全球已开展的监测项目、进展及现存科学问题,指出了现有研究的局限性,包括缺乏污水中新型冠状病毒的分布特征及感染性研究、预测预警模型开发与应用不足等. 为我国下一阶段新冠肺炎疫情或者未来可能出现的突发重大疫情的精准防控提供借鉴与参考,提升我国应对传染病及非传染病的预测预警、流行规模评估及精准施策的能力.      

Number of COVID-19 cases required in a population to detect SARS-CoV-2 RNA in wastewater in the province of Alberta, Canada: Sensitivity assessment

With a unique and large size of testing results of 1,842 samples collected from 12 wastewater treatment plants (WWTP) for 14 months through from low to high prevalence of COVID-19, the sensitivity of RT-qPCR detection of SARS-CoV-2 RNA in wastewater that correspond to the communities was computed by using Probit analysis. This study determined the number of new COVID-19 cases per 100,000 population required to detect SARS-CoV-2 RNA in wastewater at defined probabilities and provided an evidence-based framework of wastewater-based epidemiology surveillance (WBE). Input data were positive and negative test results of SARS-CoV-2 RNA in wastewater samples and the corresponding new COVID-19 case rates per 100,000 population served by each WWTP. The analyses determined that RT-qPCR-based SARS-CoV-2 RNA detection threshold at 50%, 80% and 99% probability required a median of 8 (range: 4-19), 18 (9-43), and 38 (17-97) of new COVID-19 cases /100,000, respectively. Namely, the positive detection rate at 50%, 80% and 99% probability were 0.01%, 0.02%, and 0.04% averagely for new cases in the population. This study improves understanding of the performance of WBE SARS-CoV-2 RNA detection using the large datasets and prolonged study period. Estimated COVID-19 burden at a community level that would result in a positive detection of SARS-CoV-2 in wastewater is critical to support WBE application as a supplementary warning/monitoring system for COVID-19 prevention and control.     

Adverse perinatal outcome in patients screen-positive for neural tube defects and fetal down syndrome

An association between various abnormal mid-trimester maternal serum analyte values and adverse perinatal outcome has been reported. From an original sample of 14 857 women, we observed five women who were ‘screen-positive’ for both neural tube defects [maternal serum alpha-fetoprotein (MSAFP) ≥2·5 multiples of the median] and Down syndrome [risk ≥1/274 using MSAFP, maternal serum unconjugated oestriol (MSuE3), maternal serum human chorionic gonadotropin (MShCG), and maternal age]. The four patients who elected to undergo amniocentesis all demonstrated both normal karyotype and normal amniotic fluid AFP levels. All five cases were associated with intrauterine growth retardation (IUGR) and abnormal pregnancy outcomes. Two cases exhibiting severe IUGR on ultrasound examination were terminated at 19·1 and 21·2 weeks, respectively; the former also exhibited fetal calcifications and positive maternal serology for toxoplasmosis. In another case, fetal demise occurred at 36 weeks' gestation in a patient who had been treated for syphilis in the second trimester. Neither infection was confirmed in fetal tissue studies. Though resulting in live births, the remaining two cases required operative deliveries; emergency Caesarean sections for fetal distress were performed at 38 and 32 weeks, respectively, the latter case being associated with severe pre-eclampsia. We conclude that elevated mid-trimester MSAFP levels concurrent with maternal serum analyte values associated with increased risk for fetal Down syndrome may presage a poor perinatal outcome, particularly IUGR and possibly congenital infection.     

Environment and COVID-19 incidence: A critical review

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented worldwide health crisis. Many previous research studies have found and investigated its links with one or some natural or human environmental factors. However, a review on the relationship between COVID-19 incidence and both the natural and human environment is still lacking. This review summarizes the inter-correlation between COVID-19 incidence and environmental factors. Based on keyword searching, we reviewed 100 relevant peer-reviewed articles and other research literature published since January 2020. This review is focused on three main findings. One, we found that individual environmental factors have impacts on COVID-19 incidence, but with spatial heterogeneity and uncertainty. Two, environmental factors exert interactive effects on COVID-19 incidence. In particular, the interactions of natural factors can affect COVID-19 transmission in micro- and macro- ways by impacting SARS-CoV-2 survival, as well as human mobility and behaviors. Three, the impact of COVID-19 incidence on the environment lies in the fact that COVID-19-induced lockdowns caused air quality improvement, wildlife shifts and socio-economic depression. The additional value of this review is that we recommend future research perspectives and adaptation strategies regarding the interactions of the environment and COVID-19. Future research should be extended to cover both the effects of the environment on the COVID-19 pandemic and COVID-19-induced impacts on the environment. Future adaptation strategies should focus on sustainable environmental and public policy responses.     

Control of exhaled SARS-CoV-2-laden aerosols in the interpersonal breathing microenvironment in a ventilated room with limited space air stability

The Coronavirus Disease 2019 (COVID-19) highlights the importance of understanding and controlling the spread of the coronavirus between persons. We experimentally and numerically investigated an advanced engineering and environmental method on controlling the transmission of airborne SARS-CoV-2-laden aerosols in the breathing microenvironment between two persons during interactive breathing process by combining the limited space air stability and a ventilation method. Experiments were carried out in a full-scale ventilated room with different limited space air stability conditions, i.e., stable condition, neutral condition and unstable condition. Two real humans were involved to conducted normal breathing process in the room and the exhaled carbon dioxide was used as the surrogate of infectious airborne SARS-CoV-2-laden aerosols from respiratory activities. A correspondent numerical model was established to visualize the temperature field and contaminated field in the test room. Results show that the performance of a ventilation system on removing infectious airborne SARS-CoV-2-laden aerosols from the interpersonal breathing microenvironment is dependent on the limited space air stability conditions. Appropriate ventilation method should be implemented based on an evaluation of the air condition. It is recommended that total volume ventilation methods are suitable for unstable and neutral conditions and local ventilation methods are preferable for stable conditions. This study provides an insight into the transmission of airborne SARS-CoV-2-laden aerosols between persons in ventilated rooms with different limited space air stability conditions. Useful guidance has been provided to cope with COVID-19 in limited spaces.     

Fetal therapies for cytomegalovirus: What we tell prospective parents

Congenital CMV is the most common congenital infection in the developed world. Infection results in congenital disease ranging from asymptomatic infection to severe neurodevelopmental impairment, and occasionally fetal or neonatal death. Fetal infection can occur through maternal-fetal transmission during primary maternal infection or maternal reactivation or re-infection. Awareness among maternal health care providers and parents is low. The prevention of maternal CMV infection currently relies on hygiene measures, with no effective CMV vaccine or prophylactic therapies. No licensed treatment options are available to prevent maternal-fetal transmission or fetal disease. Hyperimmunoglobulin and valaciclovir have been investigated for prevention of maternal-fetal transmission or fetal treatment, with some evidence supporting consideration of maternal administration of hyperimmunoglobulin or valaciclovir therapy in certain circumstances. This article outlines the clinical evidence regarding proven preventative behavioral measures and experimental hyperimmunoglobulin and valaciclovir therapies, that is structured around common questions asked by pregnant women about CMV infection. It is aimed to help maternity health care providers counsel prospective parents about congenital CMV disease and the preventative and therapeutic strategies currently available.     

First-trimester fetal sex determination in maternal serum using real-time PCR

An Erratum has been published for this article in Prenatal Diagnosis 22(13) 2002, 1241. Fetal sex prediction can be achieved using PCR targeted at the SRY gene by analysing cell-free fetal DNA in maternal serum. Unfortunately, the results reported to date show a lack of sensitivity, especially during the first trimester of pregnancy. Therefore, determination of fetal sex by maternal serum analysis could not replace karyotype analysis following chorionic villus sampling. A new highly sensitive real-time PCR was developped to detect an SRY gene sequence in maternal serum. Analysis was performed on 121 pregnant women during the first trimester of pregnancy (mean gestational age: 11.8 weeks). Among them, 51 had at least one previous male-bearing pregnancy. Results were compared with fetal sex. SRY PCR analysis of maternal serum was in complete concordance with fetal sex. Among the 121 pregnant women, 61 were bearing a male fetus and 60 a female fetus. No false-negative results were observed. Furthermore, no false-positive results occurred, even though 27 women carrying a female fetus during the current pregnancy had at least one previous male-bearing pregnancy. This study demonstrates that a reliable, non-invasive sex determination can be achieved by PCR analysis of maternal serum during the first trimester of pregnancy. This non-invasive approach for fetal sex prediction should have great implications in the management of pregnant women who are carriers of an X-linked genetic disorder. Prenatal diagnosis might thus be performed for male fetuses only, avoiding invasive procedures and the risk of the loss of female fetuses. Copyright © 2001 John Wiley & Sons, Ltd.     

Perinatal outcome after maternal primary cytomegalovirus infection in the first trimester: a practical update and counseling aid

Cytomegalovirus (CMV) is the most common cause of congenital infection with approximately 0.5% of pregnant women in developed countries seroconverting during pregnancy. In utero transmission occurs in about one third of women who develop primary infection in the first trimester, and these fetuses are at risk for adverse perinatal outcomes and long-term neurological complications. The great promise of a prenatal therapy to reduce fetal infection after maternal primary CMV infection has not been realized to date. The prediction of CMV sequelae is particularly challenging for clinicians because of the heterogeneity of the published literature, the wide spectrum of perinatal outcomes, the adjustment of fetal risk at each stage of assessment, and the variable quality of published data. Given the continued lack of a proven fetal therapy, it is timely to review the natural history of congenital CMV in the modern management era. We have analyzed the recent literature, integrated findings from multiple studies, and calculated stage-specific risks for adverse perinatal outcome to assist in counseling women with first trimester primary CMV infection. © 2014 John Wiley & Sons, Ltd.     

Prenatal diagnosis of neural tube by measurement of serum alpha-fetoprotein defects in havana city

Prenatal screening was carried out in Havana City, Cuba, as part of a National Medical Genetics Programme, in order to detect elevated alpha-fetoprotein concentration in maternal serum (MS-AFP). A total of 97 900 pregnant women between 15 and 19 weeks of pregnancy were tested from 1982 to 1985. A double-antibody-sandwich technique was used. 173 malformed fetuses were detected. Confirmation was by ultrasonography, elevated AFP values in a second serum sample and in amniotic fluid and acetylcholinesterase. No termination of a normal pregnancy occurred. The screening of all pregnancies is easy, economical and useful for detecting not only fetuses suffering from open Neural Tube Defects (NTDs) and other severe disorders but also pregnancies at risk of further complications.     

Monitoring SARS-CoV-2 in the Wastewater and Rivers of Tapachula,a Migratory Hub in Southern Mexico

Food and Environmental Virology - The COVID-19 pandemic has been monitored by applying different strategies, including SARS-CoV-2 detection with clinical testing or through wastewater-based...     

Maternal genetic disorders and fetal development

With improvements in early diagnosis and management of genetic diseases, more women with genetic disorders are reaching reproductive age and becoming pregnant. While pregnancy can have a significant impact on a woman's health when there is an underlying genetic disorder, there can also be fetal effects, including embryopathy, fetal growth restriction, and brain injury. Some maternal genetic disorders are associated with adverse perinatal outcomes, including a high risk of perinatal loss and preterm birth. In this article, we review several maternal genetic disorders associated with fetal risk that are important for clinicians and patients to understand and manage appropriately. These include phenylalanine hydroxylase (PAH) deficiency and other inborn errors of metabolism, tuberous sclerosis complex, myotonic dystrophy, cystic fibrosis, Turner syndrome, sickle cell disease, and connective tissue disorders.     

Prospective intervention trial of a screening protocol to identify fetal trisomy 18 using maternal serum alpha-fetoprotein,unconjugated oestriol,and human chorionic gonadotropin

Two prenatal centres in New England, routinely using a screening protocol for fetal Down syndrome that included maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG) measurements in combination with maternal age, adopted a separate screening protocol for trisomy 18. That protocol identified a pregnancy as being at high risk when AFP, uE3, and hCG measurements all fell at or below specified cut-offs (0.75, 0.60, and 0.55 multiples of the median, respectively), regardless of maternal age. Among the first 19 491 women screened, 98 (0.5 per cent) were found to have values which placed them in the high-risk category. Four of these women were subsequently found not to be pregnant. In two others, samples from non-pregnant individuals were found to have been incorrectly submitted for analysis in place of the samples from the pregnant women. All of the remaining 92 women were counselled and offered amniocentesis and fetal karyotyping. Eighty-eight (96 per cent) accepted. Karyotypes or birth outcomes were available on all 92 pregnancies. Six cases of trisomy 18 and one case of Turner syndrome were identified by karyotype. One case of trisomy 18 was identified for every 14 unaffected pregnancies offered amniocentesis. In the present prospective study, an estimated 85 per cent of the cases of trisomy 18 were identified. However, given the small number ofcases (six), the 95 per cent confidence interval for the detection rate is broad (40–95 per cent).     

Increased maternal serum alpha-fetoprotein and human chorionic gonadotropin in compromised pregnancies other than for neural tube defects or Down syndrome

Intrauterine fetal death occurred in four women who were ‘screen-positive’ in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore, we evaluated all ‘screen-positive’ women in whom both of these markers were ⩾ 2.0 multiples of the median. The cases fulfilling these criteria totalled 11, and only one of them had no complications. High concentrations of both MSAFP and MShCG in a number of these cases might have been caused by an increased placental volume, which, in turn, might have been induced by decreased perfusion of the placenta. We conclude that screening programmes wrongly determine a high risk of fetal NTD or DS if the concentrations of both these parameters are very high. Invasive diagnostic procedures should be avoided in these cases, particularly in view of the increased risk of an adverse pregnancy outcome.     

Association between fetal nuchal translucency thickness in first trimester and subsequent gestational hypertension and preeclampsia

Increased fetal nuchal translucency (NT) in the first trimester is associated with adverse pregnancy outcomes. Whether the increased NT is also associated with an increased frequency of pregnancy-associated hypertension (PAH) is not known. Seven hundred and seventy-nine pregnant women who received NT-based Down syndrome screening and delivered their babies at our hospital by September 2000 were enrolled into this study. Among these women, there are 46 cases of preeclampsia, 68 cases of gestational hypertension (GH); 665 women without any adverse pregnancy outcomes served as controls. Correlation analysis demonstrated that NT MoM (multiples of median) level had a positive association with maternal diastolic blood pressure at the time of admission for delivery (r = 0.104; p < 0.01). The severity of PAH was concordant with the stepwise increase of mean NT MoM level, which was 0.88 in control, 1.07 in gestational hypertension, and 1.13 in preeclampsia (p < 0.001). Using the 95th (1.52 MoM) and 90th (1.31 MoM) percentiles of NT thickness as cut-offs, the sensitivities and odds ratios of the women at risk for developing GH after 20 weeks of gestation were 8.8%, 19.1% and 1.98, 2.15 respectively, while for preeclampsia were 10.9%, 28.3% and 2.49, 3.58 respectively. It is concluded that the pathological changes in the placenta responsible for the development of PAH may also influence the physiological decrease of NT thickness in late first trimester. However, the sensitivity of fetal NT measurement in first trimester is not sufficient as a single marker for predicting the pregnant women at risk for subsequent PAH. Copyright © 2002 John Wiley & Sons, Ltd.     

Identification of Workers at Increased Risk of Infection During a COVID-19 Outbreak in a Meat Processing Plant,France, May 2020

Food and Environmental Virology - On 13 May 2020, a COVID-19 cluster was detected in a French processing plant. Infected workers were described. The associations between the SARS-CoV-2 infection...     

甲型流感的流行与防控分析及其对新冠肺炎疫情的启示

目前新型冠状病毒肺炎（COVID-19）疫情在全球流行,对人类生命健康造成威胁.对甲型流感这一常见传染病进行流行特征、影响因素和防控措施分析,回顾总结全球为防控甲型流感做出的努力及相关科学研究成果,为新型冠状病毒肺炎疫情提供防控经验和研究思路.结果表明:①甲型流感呈季节性流行,受气候、社会、政治和文化等多因素影响,在低温低湿、人口密集的环境中表现出强流行性.②甲型流感防控研究工作主要包括季节性流感病毒监测、流感病毒的生态学研究、广谱中和抗体及通用疫苗的研究、应对流感大流行的病原学风险评估四方面,其中季节性流感病毒监测是制定公共卫生政策及后续研究的核心防控措施.③与甲型流感类似,新型冠状病毒肺炎疫情流行受温度等气候因素影响,同时社会、政治、文化等因素也影响其传播,亟需借鉴较成熟的甲型流感的防控经验、技术和平台.建议在加强病毒监测的同时,深入开展病毒生态学研究、病原学风险评估和药物开发,对完善疫情防控工作和预警预测未来可能出现的二次暴发及传播至关重要.研究结果将为新型冠状病毒肺炎疫情和未来传染病疫情的防控及预测预警提供参考和研究思路.