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      Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and –neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases

      research-article
      a , * , b , b , c , c , a , a , d , e , f , g , h , i
      Biochimica et Biophysica Acta. Molecular Basis of Disease
      Elsevier B.V.
      ACE2, Angiotensin-converting enzyme 2 receptors, AF, Amniotic Fluid, Ang 1-7, Angiotensin 1-7, APTT, Activated partial thromboplastin time, ARDS, Acute respiratory distress syndrome, AT1R, Angiotensine type 1 receptor, B/L7, Cathepsin B/L7, BV, Bacterial Vaginitis, CDC, Centers for Disease Control and Prevention, USA, CMV, Cytomegalovirus, COVID-19, Coronavirus disease 2019, CoVs, Coronaviruses, CS, Cytokine Storm, CSF, Cerebrospinal Fluid, DIC, Disseminated Intravascular Coagulation, FRC, Functional residual capacity, GFR, Glomerular filtration rate, HIV, Human Immunodeficiency Virus, HSV, Herpes Simplex Virus, ILs, Interleukins, MAS, Macrophage Activation Syndrome, MasR, Mas Receptor (for Angiotensin 1-7), MIPL, Medically Induced Premature Labor, NK, Natural Killer, NGS, Next-Generation Sequencing, NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells, PRMBL, Premature Rupture of Membranes Before Labor, RAS, Renin–angiotensin–aldosterone system, S, Spike Protein, SPL, Spontaneous Premature Labor, SVR, Systemic vascular resistance, TMPRSS2, Type II transmembrane serine protease, TORCH, Toxoplasmosis, Rubella, Cytomegalovirus and Herpes Virus-like infections, TNF-α, Tumor necrosis factor-α, WHO, World Health Organization, ZIKV, Zika Virus, viruses, bacteria, mycoplasma, pregnancy, neonates, maternal-fetal interphase

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          Abstract

          During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Detection of SARS-CoV-2 in Different Types of Clinical Specimens

            This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.
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              Structural basis of receptor recognition by SARS-CoV-2

              Summary A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans 1,2 . A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2) 3,4 . Here we determined the crystal structure of SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of hACE2. Compared with SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we showed that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.
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                Author and article information

                Journal
                Biochim Biophys Acta Mol Basis Dis
                Biochim Biophys Acta Mol Basis Dis
                Biochimica et Biophysica Acta. Molecular Basis of Disease
                Elsevier B.V.
                0925-4439
                1879-260X
                6 October 2021
                6 October 2021
                : 166285
                Affiliations
                [a ]Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Dept. of Biophysics. Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
                [b ]Dept. of Neonatology, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
                [c ]Dept. of Histology and Development, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
                [d ]Dept. of Clinical Ginecology and Obstetrics B. Facultad de Medicina, Universidad de la Republica
                [e ]Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, Universidad Católica de Chile, Santiago, Chile
                [f ]Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-, 41012, Spain. Medical School (Faculty of Medicine), Sao Paulo State University (UNESP), Brazil
                [g ]University of Queensland, Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD, 4029, Queensland, Australia
                [h ]Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713GZ, Groningen, The Netherlands
                [i ]Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, California, USA
                Author notes
                [* ]Corresponding author at: Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Department of Biophysics, Faculty of Medicine, Universidad de la República, Montevideo, Uruguay.
                Article
                S0925-4439(21)00218-0 166285
                10.1016/j.bbadis.2021.166285
                8492386
                38ad3665-9d0d-44ec-8696-1eb25c4c54e8
                © 2021 Elsevier B.V. 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.

                History
                : 25 February 2021
                : 14 September 2021
                : 1 October 2021
                Categories
                Article

                ace2, angiotensin-converting enzyme 2 receptors,af, amniotic fluid,ang 1-7, angiotensin 1-7,aptt, activated partial thromboplastin time,ards, acute respiratory distress syndrome,at1r, angiotensine type 1 receptor,b/l7, cathepsin b/l7,bv, bacterial vaginitis,cdc, centers for disease control and prevention, usa,cmv, cytomegalovirus,covid-19, coronavirus disease 2019,covs, coronaviruses,cs, cytokine storm,csf, cerebrospinal fluid,dic, disseminated intravascular coagulation,frc, functional residual capacity,gfr, glomerular filtration rate,hiv, human immunodeficiency virus,hsv, herpes simplex virus,ils, interleukins,mas, macrophage activation syndrome,masr, mas receptor (for angiotensin 1-7),mipl, medically induced premature labor,nk, natural killer,ngs, next-generation sequencing,nf-κb, nuclear factor kappa-light-chain-enhancer of activated b cells,prmbl, premature rupture of membranes before labor,ras, renin–angiotensin–aldosterone system,s, spike protein,spl, spontaneous premature labor,svr, systemic vascular resistance,tmprss2, type ii transmembrane serine protease,torch, toxoplasmosis, rubella, cytomegalovirus and herpes virus-like infections,tnf-α, tumor necrosis factor-α,who, world health organization,zikv, zika virus,viruses,bacteria,mycoplasma,pregnancy,neonates,maternal-fetal interphase

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