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      Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel

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      Frontiers in Immunology
      Frontiers Media S.A.
      pandemic, severe acute respiratory syndrome-coronavirus-2, SARS-CoV-2, agammaglobulinemia, inborn errors of immunity, primary immunodeficiency, coronavirus disease 2019, COVID-19

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          Abstract

          In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two “waves” of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.

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          Most cited references27

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          The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak

          Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.
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            Autoantibodies against type I IFNs in patients with life-threatening COVID-19

            The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science, this issue p. eabd4570, p. eabd4585; see also p. 404
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              Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults

              Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. Methods A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. Results The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. Conclusions The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                14 January 2021
                2020
                14 January 2021
                : 11
                : 614086
                Affiliations
                [1] 1 Allergy and Immunology Unit, Schneider Children's Medical Center of Israel, Felsenstein Medical Research Center, Kipper Institute of Immunology , Petach Tikva, Israel
                [2] 2 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel
                [3] 3 The Jeffrey Modell Foundation Israeli Network for Primary Immunodeficiency , New York, NY, United States
                [4] 4 Pediatric Department A and the Immunology Service, Jeffrey Modell Foundation Center, “Edmond and Lily Safra” Children‘s Hospital, Sheba Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University , Tel-Aviv, Israel
                [5] 5 Clinical Immunology, Angioedema and Allergy Unit, Center for Autoimmune Diseases, Sheba Medical Center , Tel Hashomer, Israel
                [6] 6 Sackler School of Medicine, Tel Aviv University , Ramat-Aviv, Israel
                [7] 7 Department of Medicine, Allergy and Clinical Immunology Unit, Tel Aviv Sourasky Medical Center , Tel Aviv, Israel
                [8] 8 Pediatric Allergy Unit, E. Wolfson Medical Center , Holon, Israel
                [9] 9 Pediatric Department, E. Wolfson Medical Center , Holon, Israel
                [10] 10 Ruth Children Hospital, Rappaport Faculty of Medicine, Technion , Haifa, Israel
                [11] 11 Immunology Clinic, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel
                [12] 12 Azrieli Faculty of Medicine, Bar-Ilan University , Safed, Israel
                [13] 13 Blood Coagulation Service and Pediatric Hematology Clinic, Galilee Medical Center , Nahariya, Israel
                [14] 14 Bone Marrow Transplantation Department, Hadassah-Hebrew University Medical Center , Jerusalem, Israel
                [15] 15 Department of Pediatrics, Mount Scopus Hadassah-Hebrew University Medical Center , Jerusalem, Israel
                [16] 16 Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel
                [17] 17 The Allergy and Immunology Unit, Shaare Zedek Medical Center , Jerusalem, Israel
                [18] 18 Pediatric Pulmonary Unit, Pediatric Division, Shaare Zedek Medical Center , Jerusalem, Israel
                [19] 19 Allergy and Clinical Immunology Unit, Meir Medical Center , Kfar-Saba, Israel
                [20] 20 Pediatrics B, Schneider Children Medical Center Israel, Sackler School of Medicine, Tel Aviv University , Tel Aviv, Israel
                [21] 21 Pediatric Department, Allergy and Immunology Clinic, Carmel Medical Center, Technion Faculty of Medicine , Haifa, Israel
                [22] 22 Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir (Former Assaf Harofeh) Medical Center , Zerifin, Israel
                Author notes

                Edited by: Sergio Rosenzweig, National Institutes of Health (NIH), United States

                Reviewed by: Silvia Sánchez-Ramón, Complutense University of Madrid, Spain; Thomas Arthur Fleisher, American Academy of Allergy, Asthma and Immunology, United States

                *Correspondence: Raz Somech, Raz.Somech@ 123456sheba.health.gov.il

                †These authors have contributed equally to this work

                This article was submitted to Primary Immunodeficiencies, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.614086
                7840610
                33519822
                91207e69-e423-409e-b7d3-7e5744eb0ec9
                Copyright © 2021 Marcus, Frizinsky, Hagin, Ovadia, Hanna, Farkash, Maoz-Segal, Agmon-Levin, Broides, Nahum, Rosenberg, Kuperman, Dinur-Schejter, Berkun, Toker, Goldberg, Confino-Cohen, Scheuerman, Badarneh, Epstein-Rigbi, Etzioni, Dalal and Somech

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 October 2020
                : 01 December 2020
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 30, Pages: 9, Words: 4467
                Categories
                Immunology
                Original Research

                Immunology
                pandemic,severe acute respiratory syndrome-coronavirus-2,sars-cov-2,agammaglobulinemia,inborn errors of immunity,primary immunodeficiency,coronavirus disease 2019,covid-19

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