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      Viruses and autism: A Bi-mutual cause and effect

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          Abstract

          Autism spectrum disorder (ASD) is a group of heterogeneous, multi-factorial, neurodevelopmental disorders resulting from genetic and environmental factors interplay. Infection is a significant trigger of autism, especially during the critical developmental period. There is a strong interplay between the viral infection as a trigger and a result of ASD. We aim to highlight the mutual relationship between autism and viruses. We performed a thorough literature review and included 158 research in this review. Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism, especially for specific viral infections such as Rubella, Cytomegalovirus, Herpes Simplex virus, Varicella Zoster Virus, Influenza virus, Zika virus, and severe acute respiratory syndrome coronavirus 2. Viral infection directly infects the brain, triggers immune activation, induces epigenetic changes, and raises the risks of having a child with autism. At the same time, there is some evidence of increased risk of infection, including viral infections in children with autism, due to lots of factors. There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism. In addition, children with autism are at increased risk of infection, including viruses. Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism. Immune modulation of children with autism should be considered to reduce the risk of infection.

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          Most cited references158

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          Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016

          Problem/Condition Autism spectrum disorder (ASD). Period Covered 2016. Description of System The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (40% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively). Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). Interpretation The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. Public Health Action These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.
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            SARS-CoV-2 is associated with changes in brain structure in UK Biobank

            There is strong evidence of brain-related abnormalities in COVID-19 1–13 . However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days on average separating their diagnosis and the second scan—as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.
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              The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.

              Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.
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                Author and article information

                Contributors
                Journal
                World J Virol
                WJV
                World Journal of Virology
                Baishideng Publishing Group Inc
                2220-3249
                25 June 2023
                25 June 2023
                : 12
                : 3
                : 172-192
                Affiliations
                Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta ‎31511‎, Alghrabia, Egypt
                Department of Pediatrics, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib ‎Medical Group, Manama ‎26671‎, Bahrain. mbelrem@ 123456hotmail.com
                Medical Microbiology Section, Pathology Department, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
                Microbiology Section, Pathology Department, Irish Royal College of Surgeon, Busaiteen ‎15503‎, Muharraq, Bahrain
                Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain‎, Busiateen ‎15503‎, Muharraq, Bahrain
                Department of Pulmonolgy, Faculty of Medicine, Tanta University, Tanta ‎31527‎, Alghrabia, Egypt
                Department of Chest Disease, University Medical Center, King Abdulla Medical City, ‎Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama ‎26671‎, Bahrain
                Endocrinology and DM, William Harvey Hospital (Paula Carr Centre), Ashford TN24 0LZ, Kent, United Kingdom
                Pediatrics Research and Development, Genomics Creativity and Play Center, Manama 0000, Bahrain
                Author notes

                Author contributions: Al-Biltagi M, Saeed NK, Elbeltagi R, Bediwy AS, Aftab S, and Alhawamdeh R contributed equally to this work; all the authors worked together to; collect the data and write and revise the manuscript.

                Corresponding author: Mohammed Al-Beltagi, MBChB, MD, MSc, PhD, Academic Editor, Chairman, Consultant Physician-Scientist, Professor, Researcher, Department of Pediatrics, Faculty of Medicine, Tanta University, Al bahr Street, Tanta ‎31511‎, Alghrabia, Egypt. mbelrem@ 123456hotmail.com

                Article
                jWJV.v12.i3.pg172
                10.5501/wjv.v12.i3.172
                10311578
                37396705
                c684ea90-be20-42a1-aff7-f297a9d5f217
                ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 15 February 2023
                : 16 March 2023
                : 18 April 2023
                Categories
                Review

                autism,children,rubella,cytomegalovirus,herpes simplex virus,influenza virus,‎zika virus,sars-cov-2,covid-19,viral infection

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