Congenital Virus Infection Research Articles

Chorioretinitis with retinal ablation complications in patients with cytomegalovirus infections and high myopia: a case report

Background: Chorioretinitis is uveitis that causes choroidal and retinal inflammation. Chorioretinitis in general due to cytomegalovirus (CMV) infection has been recognized as a major cause of congenital virus infections. A common complication in patients with uveitis is retinal detachment. In addition, high myopia can also cause retinal detachment.Case Illustration: We reported a 33-year-old male patient who came with chief complaints of a sudden blurred left eye the couple of weeks before admission. The patient had a history of high myopia -5D in both eyes and was HIV positive. One week before the complaint, patient underwent laser therapy because of retinal detachment and was also given Neomicin and Potassium Iodide eye drops. Patients presented with vision 1/60. In funduscopy examination, we found vasculitis, retinal detachment, bleeding and exudate. The patient was then diagnosed with OS Rhegmatogenous Retinal Detachment (RRD) caused by CMV chorioretinitis and high myopia ODS. The patient was treated with valganciclovir 1x900mg, methylprednisolone 2x32mg, prednisone eye drops 6x1 OD and underwent pars plana vitrectomy (VPP). The patient had complicated cataracts, therefore phacoemulsification, evacuation and reinjection of silicon oil and endolaser were performed. Unfortunately, the results obtained are not optimal where the patient's vision becomes the patient's no light perception (NLP).Discussion: Retinal detachment is a frequent complication in patients with CMV chorioretinitis. The main therapy is HAART, anti-CMV and operative management. This therapy regimen is proven to improve overall patients’ prognosis.Conclusion: Early diagnosis and appropriate treatment have a very important role in determining the prognosis of patients with CMV chorioretinitis.

Current practices of management of maternal and congenital Cytomegalovirus infection during pregnancy after a maternal primary infection occurring in first trimester of pregnancy: Systematic review.

Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in many countries. This systematic review aims to provide the state of the art on current practices concerning management of maternal and congenital CMV infection during pregnancy, after maternal primary infection (PI) in first trimester of pregnancy. Electronically searches on databases and hand searches in grey literature. Primary outcome was listing biological, imaging, and therapeutic management interventions in two distinct populations: population 1 are pregnant women with PI, before or without amniocentesis; population 2 are pregnant women with congenitally infected fetuses (after positive amniocentesis). Secondary outcome was pregnancy outcome in population 2. Out of 4,134 studies identified, a total of 31 studies were analyzed, with 3,325 pregnant women in population 1 and 1,021 pregnant women in population 2, from 7 countries (Belgium, France, Germany, Israel, Italy, Spain and USA). In population 1, ultrasound (US) examination frequency was 0.75/month, amniocentesis in 82% cases, maternal viremia in 14% and preventive treatment with hyperimmune globulins (HIG) or valaciclovir in respectively 14% and 4% women. In population 2, US examination frequency was 1.5/month, magnetic resonance imaging (MRI) in 44% cases at 32 weeks gestation (WG), fetal blood sampling (FBS) in 24% at 28 WG, and curative treatment with HIG or valaciclovir in respectively 9% and 8% patients. This systematic review illustrates management of maternal and congenital CMV during pregnancy in published and non-published literature, in absence of international consensus. PROSPERO CRD42019124342.

Outcome of Fetuses With Congenital Cytomegalovirus Infection and Normal Ultrasound at Diagnosis: Systematic Review and Meta-analysis

(Abstracted from Ultrasound Obstet Gynecol 2021;57:551–559) Cytomegalovirus (CMV) is the most common congenital viral infection that occurs during pregnancy. Prenatal imaging can detect some congenital anomalies associated with CMV, and the presence of a structural anomaly on ultrasound in pregnancies with CMV is associated with a high risk of symptomatic infection and abnormal neurodevelopmental outcomes.

Антенатальная и ранняя постнатальная этиологическая верификация актуальных врожденных вирусных инфекций

Nonspecificity of clinical, laboratory and instrumental manifestations of congenital infectious diseases, including viral infections, and the diversity of methods for etiological verification of pathogens define both the need to choose the optimal approaches to the diagnosis of this pathology, and the feasibility of testing for a broad range of etiologic agents in case of suspected congenital viral infection. The analysis of current guidelines, international consensus documents issued by specialists, and published results of some studies has shown that identification of the genetic material of the pathogen with the use of amniocentesis/ cordocentesis (for cytomegalovirus and parvovirus infections) or in the birth canal (for herpes simplex infection) is the key method for antenatal etiological verification of the widespread viral infections. During the postnatal period, molecular genetic testing is combined with serological diagnosis involving determining specific immunoglobulins M and G, as well as their avidity index.

Cytomegalovirus (CMV) Infection in Infants: Two Case Reports and Review of Literature

Cytomegalovirus (CMV) is a virus under the Herpesviridae family. We describe two case reports on different manifestations of infants with CMV infection presented with neonatal jaundice, small for gestational age (SGA) and congenital cataract. Congenital CMV (cCMV) was diagnosed in a neonate presented with jaundice and SGA. cCMV cannot be excluded in another case as no CMV PCR done within 3 weeks of life. Only one cCMV infection was treated with 6 weeks of ganciclovir anti-viral therapy, which presented with neonatal jaundice, SGA with a very high CMV viral load. All cases were under multidisciplinary follow[1]up, including pediatric for developmental assessments, audiologist for hearing assessment, and ophthalmology for vision assessment. These case reports describe the importance of thorough clinical examination and early screening of CMV infection in infants to rule out cCMV as CMV is the commonest congenital treatable viral infection in Malaysia. Early treatment and intervention can be planned for child wellbeing.

Quantitative RT PCR in the Diagnosis of Congenital Cytomegalovirus Infection with Special Reference to Sensorineural Hearing Loss in a Tertiary Care Centre in North Kerala

Background:- Cytomegalovirus, a Herpes virus is the most common virus causing congenital viral infections. Sensorineueal hearing loss is the most common non hereditary manifestation. Majority of the babies are asymptomatic or have non specific symptoms at birth. An early diagnosis can help in starting antiviral treatment based on the clinical disease to prevent end organ damage and to intervene early in babies with hearing impairment which can reduce long term sequelae. Objectives :- The aim of the study is to diagnose and quantitate neonatal CMV infection by qRTPCR (Quantitative Real Time Polymerase Chain Reaction) ,to evaluate the proportion and clinical profile of congenital CMV infections in a tertiary care hospital. Materials and Methods:- This cross sectional diagnostic evaluation was done in the Dept. of Microbiology and Neonatal unit of Dept of Paediatrics, Govt Medical college .Kozhikode from August 2017 to December 2018. Details of demographic data, clinical profile, and CMV viral load in urine in various clinical infections were obtained and analyzed. Urine samples from 225 babies were received and processed in the Microbiology Department. DNA isolation and amplification was performed using commercial DNA extraction kit and CMV PCR kit for detection and quantification of CMV. Results:- Of 225 babies with clinical features suggestive of CMV infection, CMV-DNA was detected and quantitated in urine of 27 babies (12%). The most common clinical presentation was hearing impairment, seen in 22 babies. Conclusion:- RT-qPCR helps in diagnosing and quantitating CMV in congenital neonatal infection which helps in deciding on therapy and assessing response to treatment,and can predict risk for long term sequelae. Diagnosis of congenital CMV in the newborn period is important for identifying those with neurologic abnormalities where appropriate treatment and management is essential. Keywords: Congenital CMV, qRTPCR, SNHL, Viral load, Urine.

Pathogenic variants in DOCK6 mimic congenital viral infection in an SGA infant with VSD and intracranial calcifications

Pathogenic variants in DOCK6 mimic congenital viral infection in an SGA infant with VSD and intracranial calcifications

Association between Viral Infections and Risk of Autistic Disorder: An Overview.

Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems, impairment of social interactions, and stereotypic behaviours. Emerging studies indicate possible associations between viral infections and neurodegenerative and neurobehavioural conditions including autism. Viral infection during critical periods of early in utero neurodevelopment may lead to increased risk of autism in the offspring. This review is aimed at highlighting the association between viral infections, including viruses similar to COVID-19, and the aetiology of autism. A literature search was conducted using Pubmed, Ovid/Medline, and Google Scholar database. Relevant search terms included “rubella and autism”, “cytomegalovirus and autism”, “influenza virus and autism”, “Zika virus and autism”, “COVID-19 and autism”. Based on the search terms, a total of 141 articles were obtained and studies on infants or children with congenital or perinatal viral infection and autistic behaviour were evaluated. The possible mechanisms by which viral infections could lead to autism include direct teratogenic effects and indirect effects of inflammation or maternal immune activation on the developing brain. Brain imaging studies have shown that the ensuing immune response from these viral infections could lead to disruption of the development of brain regions and structures. Hence, long-term follow up is necessary for infants whose mothers report an inflammatory event due to viral infection at any time during pregnancy to monitor for signs of autism. Research into the role of viral infection in the development of ASD may be one avenue of improving ASD outcomes in the future. Early screening and diagnosis to detect, and maybe even prevent ASD are essential to reduce the burden of this condition.

195 Development of a fetal porcine model for congenital viral infections in the developing CNS

To develop a porcine model for analysis of the effects of congenital viral infections on CNS and spinal (CSF) derived fetal neural precursor (NPC) and neural progenitor cells. Isolation of NPCs from the subventricular zone (SVZ) of the porcine brain or CSF derived from premature (day 104) and post-term (day 135) Cesarean-delivered piglets were plated in 12-well plates. Nonadherent plates were used to generate neurospheres with self-renewal capacity and for long term passages. After a 2-day incubation for neurosphere formation and removal of apoptotic debris, cells were seeded in various conditions including incubation in (1) 10% FBS, (2) Rock Inhibitor (RI)-specific inhibitor of apoptosis, (3) FBS and RI, and (4) Neurobasal media alone (control). After purification and identification of NPCs, cells were then infected with low MOI of clinically isolated first passage ZIKV HN16, then fixed and stained with Flavivirus-specific antibody (MAb 4G2) followed by FITC labeled secondary antibody staining visualization under fluorescence microscopy. Gene expression studies were also performed from RNA from ZIKV infected and mock infected samples to determine effects on genes related to NPC self-renewal and survival. The brain derived cells cultured for 4 days showed three distinct populations including NSCs, NPCs, and a mixed NSC/NPC population. After 21 days of culture, cells shifted from an NSC population toward later within the NPC lineage. Both brain and CSF cells showed relatively equal permissivity to ZIKV viral infection (Fig.1). Moreover, there was no difference in Vimentin gene expression in ZIKV infected cells, while SOX-2 and Nestin gene expression following ZIKV infection was significantly lower (p<0.05; Fig.2). The findings that Nestin expression is downregulated when comparing brain and CSF cells, particularly after ZIKA infection, is of interest since Nestin is postulated to play a role in axonal growth. This study demonstrated the ability to utilize porcine fetal NPCs in a safe and effective manner for the study of NPC development and effects of viral infections

A Case of Microcephaly with Congenital Retinal Detachment

Microcephaly can occur with autosomal dominant or autosomal recessive inherited pattern in a family, but more commonly it is a form of many syndromes that lead to intellectual impairment. Several reports of ocular anomalies accompanied with microcephaly vary from microphthalmia, nystagmus, cataracts, falciform retinal folds, retinal dysplasia, optic disc coloboma and optic atrophy to chorioretinal degeneration have been documented. In this report, the patient hospitalized for intrauterine growth restriction and microcephaly was diagnosed with congenital retinal detachment on fundus examination incidentally and whose result of chromosomal microarray analysis revealed about 1.4 Mb of duplication at Yq11.23 that is irrelevant with clinical symptom. The result of whole exome sequencing was not significant, either. So by enrolling the patient’s genetic information obtained through whole genome sequencing and clinical feature to the national bio big data, we plan to research on genetic disease in comparison with genetic information of similar cases continuously. The authors experienced a case of congenital retinal detachment accompanied by microcephaly without family history and regardless of congenital viral infection, this has not been reported until now.

Neurological Manifestations of Congenital Cytomegalovirus Infection at a Tertiary Care Centre from Southern India.

Background Cytomegalovirus (CMV) is a ubiquitous herpes virus. It is the most common congenital viral infection. Data on congenital CMV in India are lacking and hence the present study was undertaken. Objectives The aim of the study is to evaluate the clinical and radiological profile of neurological manifestations of congenital CMV infections in tertiary care hospital. Methods This is a retrospective chart review of the clinical and laboratory profile of congenital CMV infections presenting from January 2018 to February 2020 to a tertiary care hospital in Southern India. Details of clinical profile, serological and neuroimaging data were obtained and analyzed. Results A total of 42 cases with female preponderance (57%) were reported during the study period. The mean age of presentation was 2.9 years. Clinical features were developmental delay (81%), microcephaly (93%), seizures (33%), intrauterine growth restriction (19%), neonatal encephalopathy (10%), anemia (9%), jaundice (10%), hepato-splenomegaly (7%), and eye abnormalities (14%). Antenatal maternal fever was reported by 12%. Sensorineural hearing loss was present in 57%. Neuroimaging showed periventricular calcification (79%), cerebral atrophy (69%), ventricular dilatation (55%), malformations (26%), dysmyelination (12%), and temporal lobe cysts (5%). CMV-immunoglobulin-M positivity was seen in 14 cases (33%), urinary polymerase chain reaction for CMV was positive in 21 cases (50%), and clinical diagnosis was done in seven cases (16%). Conclusion Common findings in congenital CMV are microcephaly, developmental delay, seizures, anemia, and sensorineural hearing loss. Common neuroimaging findings are periventricular calcification, cerebral atrophy, malformation, white matter signal changes, and cysts. CMV can mimic like cerebral palsy, malformations of the brain, demyelinating disorders, and calcified leukoencephalopathies like Aicardi-Goutières syndrome.

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil.

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common—and clinically important—endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.

Parental Stress in Primary Caregivers of Children with Evidence of Congenital Zika Virus Infection in Northeastern Brazil.

Despite the well-known role of parents as caregivers, few studies have addressed their health outcomes related to the Zika virus epidemic. A cross-sectional study was carried out with 146 primary caregivers of children 15-26months of age, with laboratory and/or clinical evidence of Zika infection between August and October 2017 in three Brazilian municipalities: João Pessoa and Campina Grande in the state of Paraíba and Fortaleza in the state of Ceará. Caregivers reported on their child's life and health, family circumstances and underwent screening for stress using the Parenting Stress Index-Short Form. Children were evaluated for developmental delays and clinical outcomes. Differences in the prevalence of risk factors between caregivers with high or clinically relevant stress and those with normal stress were evaluated. Of the 146 participants, 13% (n = 19) were classified as having high or clinically relevant stress, all of them mothers. The two risk factors significantly and independently associated with high levels of stress, compared with individuals with normal stress levels, were "reporting difficulty in covering basic expenses" (adjusted OR 3.6 (95% CI 1.1-11.8; p = 0.034)) and "having a child with sleep problems" (adjusted OR 10.4 (95% CI 1.3-81.7; p = 0.026)). Some factors seem to contribute significantly more than others to the level of stress experienced by caregivers of children with evidence of Zika virus congenital infection. Interventions and preventive strategies should also target caregivers, who in turn will be able to respond to the unique characteristics of their child.

Spectrum of myelodysplastic syndrome in patients evaluated for cytopenia(s). A Report from a Reference Centre in Saudi Arabia

Background/ObjectiveMyelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis, peripheral cytopenias along with hypercellularity of the bone marrow, and marked dysplastic features. Establishing MDS diagnosis is difficult due to nonspecific clinical presentation and imprecise morphological criteria. In anticipation to improve the diagnostic approach in this field, we aimed to characterize the clinical and morphological features of patients presented with cytopenias with a special focus on MDS. MethodsWe comprehensively reviewed all medical record of patients who were referred to the hematology laboratory at KFSH-RC, Riyadh, Saudi Arabia, between January 2009 and March 2016 for evaluation of bone marrow aspirates and trephine biopsies due to severe and persistent cytopenia(s) to rule out MDS. ResultsA total of 183 patients, 155 adult and 28 pediatric, were identified. In the adult group, MDS was diagnosed in 82 (52.9%) patients, with a male-to-female (M:F) ratio of 1.6:1 and mean age at diagnosis of 50 years. According to the World Health Organization (WHO) 2017 criteria, MDS subtypes were as follows: MDS with single lineage dysplasia (SLD, 5%), MDS with ring sideroblasts and SLD (MDS-RS-SLD 7%), MDS with multilineage dysplasia (MDS-MLD 21%), MDS with deletion of chromosome 5q (MDS del(5q), 2%), MDS unclassifiable (MDS-U7%), hypoplastic MDS (h-MDS 4%), MDS with excess blasts-1 (MDS-EB1, 20%), MDS with excess blasts-2 (MDS- EB2, 28%), and therapy-related MDS (6%). Laboratory and morphological features were described. In both groups, cytogenetic abnormalities were classified according to the Revised International Prognostic Scoring System cytogenetic risk groups. In adults, the dominating cytogenetic abnormalities were monosomy 5 and monosomy 7 seen in 20.7% and 24.4% of patients, respectively. Peripheral cytopenia not due to MDS was diagnosed in 54 (34.8%) patients, with a mean age of 43 years and M:F ratio of 1:1. The cause of these cytopenias were as follows: bone marrow failure (BMF, 22%), peripheral destruction (20%), drug induced (20%), anemia of chronic disease (16%), B12 deficiency (7%), infection (7%), paroxysmal nocturnal hemoglobinuria (4%), idiopathic cytopenia of undetermined significance (2%), and idiopathic dysplasia of undetermined significance (2%). A definite diagnosis of MDS was not possible in 19 patients due to insufficient clinical data. In the pediatric group, MDS was diagnosed in 14/28 (50%) patients, with M:F ratio of 1.8:1 and mean age at diagnosis of 4 years. MDS subtypes (WHO 2017) in 14 patients were as follows: refractory cytopenia of childhood (RCC, 42.8%), MDS-EB1 (42.8%), and MDS-EB2 (14.2%). Laboratory and morphological features were described. The prevalent cytogenetic abnormality was monosomy 7 in six/14 (42.8%) patients. Cytopenias due to other causes were diagnosed in eight/28 patients (28.5%), with a mean age of 6.5 years and M:F ratio of 1.6:1. The causes of non-MDS related cytopenia were: congenital BMF (4 patients), peripheral destruction (2 patients), immune deficiency (1 patient), and viral infection (1 patient). A definite diagnosis of MDS could not be made in six/28 (21.4%) patients. ConclusionMDS is the cause of cytopenia in a significant number of patients referred for evaluation of cytopenias, appears at younger age, and tends to be more aggressive than that reported in international studies. Anemia, dysplastic neutrophils in the peripheral blood, and dysplastic megakaryocytes in the bone marrow trephine biopsy are the most reliable features in distinguishing MDS from other alternative diagnoses.

Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment.

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.

Fortieth week

Next month, it will have been 9 months since the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), that is, the length of a full-term pregnancy. What can be expected? Perhaps favorable outcomes, such as the following: 1) there is a lack of viral transmission to the fetus; 2) there is a failure to produce malformations in the fetal central nervous system during the "fetal moment," that is, the period when the fetus or its parent becomes infected; 3) the fetus is immune to the virus; and 4) the fetus inherits acquired immunity from its mother during the infection period. These questions are pertinent, and the ability to address them is attributable to the speed at which our Chinese colleagues identified this new mutated virus. Their efforts in this regard are much appreciated. The same was not achieved when we encountered the Zika virus epidemic, during which it took us a considerable time to correlate microcephaly with congenital viral infection.&#x0D; To date, we have counted more than 18 million confirmed cases on the planet, including over 680,000 deaths. Will the fetuses of infected pregnant mothers be spared? On reviewing works published in English and Chinese languages, we managed to identify only four cases of probable mother-to-child vertical transmission, one of which was identified at 30 h of life. However, in most of these cases, maternal contamination occurred in the third trimester of pregnancy. What is the real damage to the fetus' central nervous system when contamination occurs during embryogenesis? Such questions will surely be addressed in the imminent months.&#x0D; This pandemic has also revealed to us the fragility of our health service, considering the relatively high mortality rates obtained in well-equipped intensive care units (ICUs) with well-trained medical staff, facilities which are scarce in many regions of our country.&#x0D; Two groups of patients have been of major concern to us: pregnant women and newborns. First, results have already revealed that pregnant Brazilian women who became infected with the new coronavirus had a mortality rate 3.4 times higher than that of uninfected pregnant women. Could genetic factors, immunological factors, or failure to follow up during the puerperal period have contributed to this outcome?&#x0D; However, newborns seem to be protected. Due to the vaccine load they receive, they can build immunity against coronavirus; even a small amount of angiotensin-converting enzyme 2 (ACE-2), which is a co-receptor for the entry of the virus into cells (located mainly in the lungs, intestine, and heart) may block the early stages of infection by binding to the spike protein, preventing it from entering the cells. Alternatively, even a repeated number of viral infections could cause natural immunity. Nonetheless, this protection has not manifested in indigenous children, who are often malnourished and extremely vulnerable to respiratory infections. The mortality rate in the indigenous child and adolescent population is 7.5 per 100,000 inhabitants, which is 10 times higher than that in the same age group for other Brazilians. Therefore, the decimation of our indigenous population can be anticipated. Inevitably, the Indian population appeals for help (figure 1).&#x0D; A new multisystem inflammatory syndrome has recently been identified as a long-term effect of COVID-19, where, due to an imbalance of the inflammatory response, several tissues are affected, such as those of the gastrointestinal system as well as cardiovascular, hematological, cutaneous, respiratory, and neurological tissues. Overall, 2% of affected children have died.&#x0D; Population growth, lack of basic sanitation, deforestation of our forest reserves, and the increase in global temperatures have contributed to the emergence of new infectious epidemics and pandemics. Yellow fever, Ebola, Dengue fever, Chikungunya, Zika, H1N1, H1N2, Middle East respiratory syndrome (MERS), and SARS are simply precursors of what lies ahead. This presents yet another great challenge for humanity, especially those who survive the next 4 million years on Earth.

Recognition of a highly conserved glycoprotein B epitope by a bivalent antibody neutralizing HCMV at a post-attachment step.

Human cytomegalovirus (HCMV) is one of the main causative agents of congenital viral infection in neonates. HCMV infection also causes serious morbidity and mortality among organ transplant patients. Glycoprotein B (gB) is a major target for HCMV neutralizing antibodies, yet the underlying neutralization mechanisms remain largely unknown. Here we report that 3-25, a gB-specific monoclonal antibody previously isolated from a healthy HCMV-positive donor, efficiently neutralized 14 HCMV strains in both ARPE-19 cells and MRC-5 cells. The core epitope of 3-25 was mapped to a highly conserved linear epitope on antigenic domain 2 (AD-2) of gB. A 1.8 Å crystal structure of 3-25 Fab in complex with the peptide epitope revealed the molecular determinants of 3-25 binding to gB at atomic resolution. Negative-staining electron microscopy (EM) 3D reconstruction of 3-25 Fab in complex with de-glycosylated postfusion gB showed that 3-25 Fab fully occupied the gB trimer at the N-terminus with flexible binding angles. Functionally, 3-25 efficiently inhibited HCMV infection at a post-attachment step by interfering with viral membrane fusion, and restricted post-infection viral spreading in ARPE-19 cells. Interestingly, bivalency was required for HCMV neutralization by AD-2 specific antibody 3-25 but not the AD-4 specific antibody LJP538. In contrast, bivalency was not required for HCMV binding by both antibodies. Taken together, our results reveal the structural basis of gB recognition by 3-25 and demonstrate that inhibition of viral membrane fusion and a requirement of bivalency may be common for gB AD-2 specific neutralizing antibody.

Diagnosis of intrauterine parvovirus B19 infection at birth - Value of DNA detection in neonatal blood and dried blood spots.

Diagnosis of congenital viral infection at birth is generally attempted by direct detection of the virus by PCR in various neonatal materials. How to reliably diagnose intrauterine infection with parvovirus B19 (B19 V) at birth is unknown. To evaluate the performance of B19 V DNA detection in cord blood (CB) or neonatal dried blood spots (DBS) in diagnosing fetal infection. Two cohorts of children diagnosed prenatally with an intrauterine B19 V infection were included in this study. CB samples of intrauterine B19 V infections that were sent to a reference laboratory for congenital infections in Stuttgart, Germany in the period 1995-2014 were tested in triplicate for B19 V DNA by quantitative PCR. DBS from children with intrauterine B19 V infection that underwent IUT at the LUMC, Leiden, the Netherlands in the period 2009-2014 were tested for B19 V DNA by quantitative B19 V PCR in triplicate. Fourteen of twenty (70 %) CB samples tested positive for B19 V DNA. The positivity rate was 40 % (4/10) in those with a prenatal diagnosis <20 weeks gestation. When intrauterine B19 V infection was diagnosed thereafter, 100 % (10/10) samples were B19 V DNA positive. Of the thirteen available DBS, twelve (92 %) tested positive. Viral load in CB and DBS corresponded inversely with time from fetal diagnosis to birth. B19 V DNA can be detected in neonatal blood samples of children following intrauterine B19 V infection, although the possibility of false-negatives, even in severe infections, should be considered. B19 V viral load at birth correlates with timing of infection.

Evolution of awareness and knowledge of congenital cytomegalovirus infection among health care providers in France between 2011 and 2018.

Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection. Approximately 1 % of newborns are congenitally infected and in up to 10 % of them the consequences are severe. Antenatal and postnatal treatments, although promising, are still under evaluation. Hygiene counseling to prevent CMV infection is important and should be systematic. To evaluate health care providers' awareness of CMV maternal and congenital infection in France. A questionnaire on CMV infection was sent in 2018 by e-mail to obstetricians, pediatricians, midwives and laboratory physicians, and members of medical or midwifery associations. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and long-term effects (scores from 0 to 30) and compared the results with those of our 2012 published study. Of the 597 respondents who completed the questionnaire, 91 % were unaware of the precise transmission route of CMV, 33 % wrongly thought thatin utero therapy for congenital CMV infection was a current standard of care in France, and less than half were familiar with the HAS (Haute Autorité de Santé) and CNGOF (Collège National des Gynécologues et Obstétriciens Français) recommendations. When respondents' knowledge of CMV was greater, patients were given more hygiene counseling. Between 2011 and 2018, knowledge improved among doctors and midwives concerning the route of transmission, the symptoms in adults, and the long-term effects of CMV infection. Knowledge is improving among healthcare providers, but gaps remain. To bridge these gaps, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet. Moreover, greater knowledge will allow for more effective counseling of pregnant women, as recommended by HCSP and CNGOF in France.

Human cytomegalovirus preferentially infects early gestation placental macrophages and evades their antiviral immunogenicity through evasion of the type I IFN response

Abstract Human cytomegalovirus (HCMV) is the leading cause of congenital viral infections. When a pregnant woman develops primary HCMV infection in early gestation, the risk of transplacental infection is ~40%. Studies have documented the presence of HCMV in placental macrophages (Hofbauer cells [HCs]) as a consequence of maternal viremia. However, the interplay between HCMV and placental macrophages (HCs) is poorly defined. With written informed consent, placentae were collected from 12 HIV-1/Hep B/HCMV seronegative women (&amp;gt;18 years). HCs were exposed to human HCMV (TB40/E). qPCR, FACS, ELISA, and Western blot analysis determined the expression of activation markers, cytokines, antiviral genes, and host proteins. Here we found that HCs isolated from early gestation (15–23 weeks) placentae are more susceptible to HCMV infection than HCs isolated from term (&amp;gt;39 weeks) placentae. HCMV infection of early gestation HCs led to a significant upregulation of activation markers, along with elevated secretion of proinflammatory cytokines, compared to HCMV-infected term HCs. In early gestation and term HC, HCMV rapidly induces the type I IFN pathway, leading to secretion of IFNs and strong induction of ISGs. However, HCMV diminishes type I IFN-mediated phosphorylation of STAT2, with early gestation HCs exhibiting the greatest level of inhibition. Our findings show that HCMV can subvert type I IFN signaling to support viral growth at the placenta, particularly during early gestation. Studying mechanisms used by viruses to prevent an immune response is of great importance for the development of new strategies to limit the sequelae of viral infections.