Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Funding Information: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21-RHUS-08 (COVIFERON), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government's Investissement d'Avenir program, Laboratoires d'Excellence "Integrative Biology of Emerging Infectious Diseases" (ANR-10-LABX-62-IBEID) and "Milieu Intérieur" (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A. Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20-01333 and COV20-01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and "Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19"). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M.P, M.L.D., and J.P.-T. was funded by the European Commission-NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA. A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union's Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444; a George Mason University Fast Grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Meyer Foundation; and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Publisher Copyright: © 2023 American Association for the Advancement of Science. All rights reserved.Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.publishersversionpublishe

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

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Effectiveness of CoronaVac in preventing COVID-19 in healthcare workers

The CoronaVac vaccine was found to be effective against symptomatic COVID-19 and protective against severe disease in phase 3 studies. However, there are little data about its effectiveness in real-world conditions. The aim of the current study was to investigate the protective effect of the CoronaVac vaccine in health-care workers (HCWs) in Turkey, a country where CoronaVac is widely used. The questionnaire was sent to all employees in the form of a survey link by using a telephone application. In the survey, HCWs were asked about demographic characteristics; CoronaVac vaccination status, history of a COVID-19 infection, whether COVID-19 infection was before or after the CoronaVac vaccination; the time between being vaccinated and the COVID-19 infection; the clinical pictures of COVID-19 infection. Those who experienced COVID-19 before vaccination were compared with the breakthrough cases in terms of demographic and clinical features. A total of 628 HCW agreed to participate in the study. A total of 536 (85.3%) volunteers had been vaccinated and 92 (14.6%) had not been vaccinated against COVID-19 with CoronaVac. There was a history of COVID-19 infection in 234 (37.2%) subjects and 188 (35%) had been vaccinated and 46 (50%) not vaccinated. The rate experiencing COVID-19 disease was significantly lower in the vaccinated than the unvaccinated volunteers. The rate of breakthrough cases after CoronaVac was found to be 7%. The hospitalization rate was similar in the breakthrough cases and those who had COVID-19 before CoronaVac vaccination. The results of our study indicate that CoronaVac provides protection against COVID-19

Eosinophilic leukemoid reaction in a male adolescent with Löeffler syndrome

The Löeffler syndrome is characterized by pulmonary infiltrates on a chest x-ray accompanied with peripheral eosinophilia. In this article, we have highlighted the Löeffler syndrome complicated with a eosinophilic leukemoid reaction in a previously healthy boy. The patient was treated with albendazole for five days, with a successful result. In countries where parasitic diseases are endemic, the Löeffler syndrome must always be considered in patients who present with a eosinophilic leukemoid reaction

How does the immunogenicity of hepatitis B vaccine change over the years in childhood?

Hepatitis B is the leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. The incidence of HBV infection has significantly decreased with hepatitis B vaccination. Hepatitis B vaccine is administered to children at 0, 1 and 6 months of age according to the national schedule. There is a high rate of protective antibody (anti-HBs) development after hepatitis B vaccination. We conducted the study to investigate how the hepatitis B surface antibody (anti-HBs) positivity rates and the titers change over time in childhood following vaccination. Patients who presented at the general pediatric outpatient clinic of Yenimahalle Education and Training Hospital and the HBsAg and anti-HBs titers were tested for any reason between July 2011 and May 2018 were retrospectively evaluated. The cutoff level for protection by the anti-HBs titer was accepted as ≥10 mIU/mL with lower levels indicating no protection. Anti-HBs positivity was compared by age group. Anti-HBs levels were studied in 4326 children. The mean age of the included in the study was 127 ± 62 months. A protective anti-HBs level (≥10 mIU/mL) was present in 2292 children (69.2%). The highest anti-HBs antibody positivity rate was in the under 3 years’ age group. The positivity rate significantly decreased after age 7 years. The HBsAg level was determined in all children in the study and five had a positive result. In conclusion, our study found that the anti-HBs positivity rate and the anti-HBs level decreased with age. However, the anti-HBs antibody result remained positive in more than half of the children

An Interesting Fistula Tract Presenting with Recurrent Gluteal Abscess: Instructive Case

A fistula extending from the gluteus to penis is an extremely rare entity. In this paper, we have highlighted novel variant of congenital penile to gluteal fistula complicated with gluteal and penoscrotal abscess in a previously healthy boy. A fistulous tract extending from the gluteus to penis has been shown by fistulogram. Bleomycin has been used in fistula tract with successful results in our patient

Miliary tuberculosis disease complicated by Pott′s abscess in an infant: Seven year follow-up

A 20-month-old boy presented with 1-year history of persistent fever, cough, and progressive abdominal distention. Abdominal ultrasonography showed hepatomegaly and multiple calcifications in the liver and spleen. Thoracic computed tomography showed multiple mediastinal lymph nodes and consolidation in both lungs. Additionally, there was a 2-cm thick retroperitoneal soft tissue mass destroying the T7-8 and L1-L2 vertebral bodies. The patient was preliminarily diagnosed with miliary tuberculosis (TB) and Pott′s disease, and began administering anti-TB treatment consisting of isoniazid, rifampin, ethambutol, and pyrazinamide. Acid-resistant bacilli analysis and mycobacterial culture of the biopsy specimen of Pott′s abscess were positive. Mycobacterial culture and PCR of gastric aspirate were also positive. The patient′s condition progressively improved with anti-TB treatment and he received 12 months of antiTB therapy. At the end of the treatment all of the patient′s symptoms were relieved and he was well except for kyphosis. Miliary TB complicated by Pott′s abscess is a very rare presentation of childhood TB. The presented case shows that when Pott′s abscess is diagnosed and surgically corrected without delay, patients can recover without squeal

Chryseobacterium indologenes Septicemia in an Infant

Chryseobacterium indologenes is a rare cause of infection in children. The organism causes infections mostly in hospitalised patients with severe underlying diseases. The choice of an effective drug for the treatment of infections due to C. indologenes is difficult as the organism has a limited spectrum of antimicrobial sensitivity. We present a case of nosocomial septicemia caused by C. indologenes in an infant with congenital heart disease who was successfully treated with trimethoprim sulfamethoxazole and also reviewed fourteen additional cases of C. indologenes infections reported in the English literature in this report

Pediatricians' attitudes in management of acute otitis media and ear pain in Turkey

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