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      What are the risks of COVID-19 infection in pregnant women?

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      a , b , c , d
      Lancet (London, England)
      Elsevier Ltd.

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          Abstract

          Since December, 2019, the outbreak of the 2019 novel coronavirus disease (COVID-19) infection has become a major epidemic threat in China. As of Feb 11, 2020, the cumulative number of confirmed cases in mainland China has reached 38 800, with 4740 (12·2%) cured cases and 1113 (2·9%) deaths; additionally, there have been 16 067 suspected cases so far. 1 All 31 provinces in mainland China have now adopted the first-level response to major public health emergencies. The National Health Commission of China has published a series of guidelines on the prevention, diagnosis, and treatment of COVID-19 pneumonia, based on growing evidence of the pathogens responsible for COVID-19 infection, as well as the epidemiological characteristics, clinical features, and the most effective treatments.2, 3, 4 The central government and some provincial governments have provided food and medical supplies and dispatched expert groups and medical teams to manage and control the outbreak response in the hardest-hit areas (Wuhan and neighbouring cities in Hubei province). As the COVID-19 outbreak unfolds, prevention and control of COVID-19 infection among pregnant women and the potential risk of vertical transmission have become a major concern. More evidence is needed to develop effective preventive and clinical strategies. The latest research by Huijun Chen and colleagues 5 reported in The Lancet provides some insight into the clinical characteristics, pregnancy outcomes, and vertical transmission potential of COVID-19 infection in pregnant women. Although the study analysed only a small number of cases (nine women with confirmed COVID-19 pneumonia), under such emergent circumstances these findings are valuable for preventive and clinical practice in China and elsewhere. Although neonatal nasopharyngeal swab samples have been collected in some hospitals across China, this study also collected and tested amniotic fluid, cord blood, and breastmilk samples for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus allowing a more detailed assessment of the vertical transmission potential of COVID-19 infection. SARS-CoV-2 is a new strain of coronaviruses that are pathogenic to humans. Another two notable strains are SARS-CoV and the Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). A study done by Roujian Lu and colleagues 6 found that although SARS-CoV-2 is genetically closer to two bat-derived SARS-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21 (with about 88% genome sequence identity), than to SARS-CoV-1 (about 79% identity) and MERS-CoV (about 50% identity), homology modelling has revealed that SARS-CoV-2 has a similar receptor-binding domain structure to that of SARS-CoV-1, which suggests that COVID-19 infection might have a similar pathogenesis to SARS-CoV-1 infection.6, 7, 8 Thus, the risk of vertical transmission of COVID-19 might be as low as that of SARS-CoV-1. The present study by Chen and colleagues did not find any evidence of the presence of SARS-CoV-2 viral particles in the products of conception or in neonates, in accordance with the findings of a previous study on SARS-CoV-1 done by Wong and colleagues. 9 Two neonatal cases of COVID-19 infection have been confirmed so far, 10 with one case confirmed at 17 days after birth and having a close contact history with two confirmed cases (the baby's mother and maternity matron) and the other case confirmed at 36 h after birth and for whom the possibility of close contact history cannot be excluded. However, no reliable evidence is as yet available to support the possibility of vertical transmission of COVID-19 infection from the mother to the baby. © 2020 Soe Zeya Tun/Reuters 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Previous studies have shown that SARS during pregnancy is associated with a high incidence of adverse maternal and neonatal complications, such as spontaneous miscarriage, preterm delivery, intrauterine growth restriction, application of endotracheal intubation, admission to the intensive care unit, renal failure, and disseminated intravascular coagulopathy.9, 11 However, pregnant women with COVID-19 infection in the present study had fewer adverse maternal and neonatal complications and outcomes than would be anticipated for those with SARS-CoV-1 infection. Although a small number of cases was analysed and the findings should be interpreted with caution, the findings are mostly consistent with the clinical analysis done by Zhu and colleagues 12 of ten neonates born to mothers with COVID-19 pneumonia. The clinical characteristics reported in pregnant women with confirmed COVID-19 infection are similar to those reported for non-pregnant adults with confirmed COVID-19 infection in the general population and are indicative of a relatively optimistic clinical course and outcomes for COVID-19 infection compared with SARS-CoV-1 infection.13, 14 Nonetheless, because of the small number of cases analysed and the short duration of the study period, more follow-up studies should be done to further evaluate the safety and health of pregnant women and newborn babies who develop COVID-19 infection. As discussed in the study, pregnant women are susceptible to respiratory pathogens and to development of severe pneumonia, which possibly makes them more susceptible to COVID-19 infection than the general population, especially if they have chronic diseases or maternal complications. Therefore, pregnant women and newborn babies should be considered key at-risk populations in strategies focusing on prevention and management of COVID-19 infection. Based on evidence from the latest studies and expert recommendations, as well as previous experiences from the prevention and control of SARS, the National Health Commission of China launched a new notice on Feb 8, 2020, 15 which proposed strengthening health counselling, screening, and follow-ups for pregnant women, reinforcing visit time and procedures in obstetric clinics and units with specialised infection control preparations and protective clothing, and emphasised that neonates of pregnant women with suspected or confirmed COVID-19 infection should be isolated in a designated unit for at least 14 days after birth and should not be breastfed, to avoid close contact with the mother while she has suspected or confirmed COVID-19 infection. We need to further strengthen our capacity to deal with emergent infectious disease outbreaks, through laws and regulations to prevent and control the spread of infectious diseases and to avoid outbreak clusters in families, communities, and other public places, and to do so with transparency and solidarity. Timely reporting and disclosure of emergent infectious diseases is also important to avoid delayed responses. Infection control and management procedures in hospitals and other places with several confirmed cases isolated together should also be maintained, and specialised clothing and equipment provided to protect medical professionals and other health workers from occupational exposure to COVID-19 infection.

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          Most cited references6

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          Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

          Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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            Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

            Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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              Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

              Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier Ltd.
                0140-6736
                1474-547X
                12 February 2020
                7-13 March 2020
                12 February 2020
                : 395
                : 10226
                : 760-762
                Affiliations
                [a ]Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
                [b ]National Clinical Research Center for Obstetrics and Gynecology, Beijing 100191, China
                [c ]Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
                [d ]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
                Article
                S0140-6736(20)30365-2
                10.1016/S0140-6736(20)30365-2
                7158939
                32151334
                6aa143f8-b67d-43f3-8b68-f7d0ed691089
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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