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2. Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children

Author

Nygaard, Ulrikka, Nielsen, Annelaura Bach, Dungu, Kia Hee Schultz, Drici, Lylia, Holm, Mette, Ottenheijm, Maud Eline, Nielsen, Allan Bybeck, Glenthøj, Jonathan Peter, Schmidt, Lisbeth Samsø, Cortes, Dina, Jørgensen, Inger Merete, Mogensen, Trine Hyrup, Schmiegelow, Kjeld, Mann, Matthias, Vissing, Nadja Hawwa, and Wewer Albrechtsen, Nicolai J.

Published
2024
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5. Dangers of Herpesvirus Infection in SLE Patients Under Anifrolumab Treatment: Case Reports and Clinical Implications.

Author

Larsen, Mads Lamm, Skouboe, Morten Kelder, Mogensen, Trine Hyrup, Laursen, Alex Lund, Deleuran, Bent, Troldborg, Anne, and Bendix Rasch, Mads Nyhuus

Subjects
SYSTEMIC lupus erythematosus, DRUG side effects, HERPESVIRUS diseases, RESPIRATORY infections, HERPES simplex virus, HERPES zoster
Abstract

Background: Anifrolumab, a monoclonal antibody targeting the type 1 interferon (IFN-I) signaling pathway, holds promise as a therapeutic intervention for systemic lupus erythematosus (SLE). However, its use is associated with an increased risk of infections, particularly viral infections like herpes zoster (HZ). Results from the clinical trials on anifrolumab show yearly rates of upper respiratory tract infections of 34% and HZ of 6.1%. An increased frequency of other specific viral infections, including herpes simplex virus (HSV), was not reported. Case Reports: Here, we present 2 cases of patients with SLE treated with anifrolumab, both experiencing severe adverse reactions in the form of disseminated herpesvirus infections, specifically disseminated HSV-2 and varicella zoster virus (VZV, HZ encephalitis). To the best of our knowledge, no previous reports of severe disseminated HSV-2 or HZ have been published in anifrolumab-treated patients. The patient in case 1 experienced a primary HSV-2 infection following anifrolumab treatment, potentially explaining the severity of the infection. The patient in case 2 had a history of previous HZ skin infections, which may have increased her risk of disseminated infection. Both patients recovered from the infections with minor sequelae, but they still require prophylactic antiviral treatment. These cases highlight the critical role of IFN-I immunity in protecting against herpesvirus infections. Conclusions: Thorough risk assessment before anifrolumab initiation, considering the patient's viral infection history, vaccination status, and potential exposure risks, is essential. Administration of recombinant zoster vaccine before anifrolumab therapy may benefit susceptible individuals. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis

Author

Lafaille, Fabien G., Harschnitz, Oliver, Lee, Yoon Seung, Zhang, Peng, Hasek, Mary L., Kerner, Gaspard, Itan, Yuval, Ewaleifoh, Osefame, Rapaport, Franck, Carlile, Thomas M., Carter-Timofte, Madalina E., Paquet, Dominik, Dobbs, Kerry, Zimmer, Bastian, Gao, Daxing, Rojas-Duran, Maria F., Kwart, Dylan, Rattina, Vimel, Ciancanelli, Michael J., McAlpine, Jessica L., Lorenzo, Lazaro, Boucherit, Soraya, Rozenberg, Flore, Halwani, Rabih, Henry, Benoit, Amenzoui, Naima, Alsum, Zobaida, Marques, Laura, Church, Joseph A., Al-Muhsen, Saleh, Tardieu, Marc, Bousfiha, Ahmed Aziz, Paludan, Søren R., Mogensen, Trine Hyrup, Quintana-Murci, Lluis, Tessier-Lavigne, Marc, Smith, Gregory A., Notarangelo, Luigi D., Studer, Lorenz, Gilbert, Wendy, Abel, Laurent, Casanova, Jean-Laurent, and Zhang, Shen-Ying

Published
2019
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8. Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

Author

Petersen, Pelle Trier, Bodilsen, Jacob, Jepsen, Micha Phill Grønholm, Hansen, Birgitte Rønde, Storgaard, Merete, Larsen, Lykke, Helweg‐Larsen, Jannik, Wiese, Lothar, Lüttichau, Hans Rudolf, Andersen, Christian Østergaard, Mogensen, Trine Hyrup, Nielsen, Henrik, and Brandt, Christian Thomas

Subjects
MENINGITIS, HERPES simplex virus, COHORT analysis, LEUKOCYTE count, HUMAN herpesvirus 2
Abstract

Background and purpose: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. Methods: This was a nationwide population‐based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV‐2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single‐episode HSV‐2 meningitis were included for comparison. Results: Forty‐seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single‐episode HSV‐2 meningitis were included. The progression risk from HSV‐2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%–30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single‐episode HSV‐2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1–4) were less frequent in BRLM at all post‐discharge follow‐up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%–12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02–15.3) for patients with three or more previous episodes of meningitis. Conclusions: Clinical features of BRLM were similar to those of single‐episode HSV‐2 meningitis, whilst post‐discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence. [ABSTRACT FROM AUTHOR]

Published
2024
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10. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

Author

Manry, Jeremy, primary, Bastard, Paul, additional, Gervais, Adrian, additional, Voyer, Tom Le, additional, Rosain, Jérémie, additional, Philippot, Quentin, additional, Michailidis, Eleftherios, additional, Hoffmann, Hans-Heinrich, additional, Eto, Shohei, additional, Garcia-Prat, Marina, additional, Bizien, Lucy, additional, Parra-Martínez, Alba, additional, Yang, Rui, additional, Haljasmägi, Liis, additional, Migaud, Mélanie, additional, Särekannu, Karita, additional, Maslovskaja, Julia, additional, de Prost, Nicolas, additional, Tandjaoui-Lambiotte, Yacine, additional, Luyt, Charles-Edouard, additional, Amador-Borrero, Blanca, additional, Gaudet, Alexandre, additional, Poissy, Julien, additional, Morel, Pascal, additional, Richard, Pascale, additional, Cognasse, Fabrice, additional, Troya, Jesus, additional, Trouillet-Assant, Sophie, additional, Belot, Alexandre, additional, Saker, Kahina, additional, Garçon, Pierre, additional, Rivière, Jacques G., additional, Lagier, Jean-Christophe, additional, Gentile, Stéphanie, additional, Rosen, Lindsey, additional, Shaw, Elana, additional, Morio, Tomohiro, additional, Tanaka, Junko, additional, Dalmau, David, additional, Tharaux, Pierre-Louis, additional, Sene, Damien, additional, Stepanian, Alain, additional, Mégarbane, Bruno, additional, Triantafyllia, Vasiliki, additional, Fekkar, Arnaud, additional, Heath, James, additional, Franco, Jose, additional, Anaya, Juan-Manuel, additional, Solé-Violán, Jordi, additional, Imberti, Luisa, additional, Biondi, Andrea, additional, Bonfanti, Paolo, additional, Castagnoli, Riccardo, additional, Delmonte, Ottavia, additional, Zhang, Yu, additional, Snow, Andrew, additional, Holland, Steve, additional, Biggs, Catherine, additional, Moncada-Vélez, Marcela, additional, Arias, Andrés, additional, Lorenzo, Lazaro, additional, Boucherit, Soraya, additional, Anglicheau, Dany, additional, Planas, Anna, additional, Haerynck, Filomeen, additional, Duvlis, Sotirija, additional, Nussbaum, Robert, additional, Ozcelik, Tayfun, additional, Keles, Sevgi, additional, Bousfiha, Aziz, additional, Bakkouri, Jalila El, additional, Ramirez-Santana, Carolina, additional, Paul, Stéphane, additional, Pan-Hammarstrom, Qiang, additional, Hammarstrom, Lennart, additional, Dupont, Annabelle, additional, Kurolap, Alina, additional, Metz, Christine, additional, Aiuti, Alessandro, additional, Casari, Giorgio, additional, Lampasona, Vito, additional, Ciceri, Fabio, additional, Barreiros, Lucila, additional, Dominguez-Garrido, Elena, additional, Vidigal, Mateus, additional, Zatz, Mayana, additional, de Beek, Diederik van, additional, Sahanic, Sabina, additional, Tancevski, Ivan, additional, Stepanovskyy, Yurii, additional, Boyarchuk, Oksana, additional, Nukui, Yoko, additional, Tsumura, Miyuki, additional, Vidaur, Loreto, additional, Tangye, Stuart, additional, Burrel, Sonia, additional, Duffy, Darragh, additional, Quintana-Murci, Lluis, additional, Klocperk, Adam, additional, Kann, Nelli, additional, Shcherbina, Anna, additional, Lau, Yu-Lung, additional, Leung, Daniel, additional, Coulongeat, Matthieu, additional, Marlet, Julien, additional, Koning, Rutger, additional, Reyes, Luis, additional, Chauvineau-Grenier, Angélique, additional, Venet, Fabienne, additional, monneret, guillaume, additional, Nussenzweig, Michel, additional, Arrestier, Romain, additional, Boudhabhay, Idris, additional, Baris-Feldman, Hagit, additional, Hagin, David, additional, Wauters, Joost, additional, Meyts, Isabelle, additional, Dyer, Adam, additional, Kennelly, Sean, additional, Bourke, Nollaig, additional, Halwani, Rabih, additional, Sharif-Askari, Fatemeh, additional, Dorgham, Karim, additional, Sallette, Jérôme, additional, Mehlal-Sedkaoui, Souad, additional, AlKhater, Suzan, additional, Rigo-Bonnin, Raúl, additional, Morandeira, Francisco, additional, Roussel, Lucie, additional, Vinh, Donald, additional, Erikstrup, Christian, additional, Condino-Neto, Antonio, additional, Prando, Carolina, additional, Bondarenko, Anastasiia, additional, Spaan, András, additional, Gilardin, Laurent, additional, Fellay, Jacques, additional, Lyonnet, Stanislas, additional, Bilguvar, Kaya, additional, Lifton, Richard, additional, Mane, Shrikant, additional, Anderson, Mark, additional, Boisson, Bertrand, additional, Béziat, Vivien, additional, Zhang, Shen-Ying, additional, Andreakos, Evangelos, additional, Hermine, Olivier, additional, Pujol, Aurora, additional, Peterson, Pärt, additional, Mogensen, Trine Hyrup, additional, Rowen, Lee, additional, Mond, James, additional, Debette, Stéphanie, additional, deLamballerie, Xavier, additional, Burdet, Charles, additional, Bouadma, Lila, additional, Zins, Marie, additional, Soler-Palacin, Pere, additional, Colobran, Roger, additional, Gorochov, Guy, additional, Solanich, Xavier, additional, Susen, Sophie, additional, Martinez-Picado, Javier, additional, Raoult, Didier, additional, Vasse, Marc, additional, Gregersen, Peter, additional, Rodríguez-Gallego, Carlos, additional, Piemonti, Lorenzo, additional, Notarangelo, Luigi, additional, Su, Helen, additional, Kisand, Kai, additional, Okada, Satoshi, additional, Puel, Anne, additional, Jouanguy, Emmanuelle, additional, Rice, Charles, additional, Tiberghien, Pierre, additional, Zhang, Qian, additional, Casanova, Jean-Laurent, additional, Abel, Laurent, additional, and Cobat, Aurélie, additional

Published
2022
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11. Coenzyme Q10 as Treatment of Post COVID-19 Condition

Author

Hansen, Kristoffer Skaalum, primary, Mogensen, Trine Hyrup, additional, Agergaard, Jane, additional, Schiøttz-Christensen, Berit, additional, Østergaard, Lars Jørgen, additional, Vibholm, Line Khalidan, additional, and Leth, Steffen, additional

Published
2022
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12. Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2

Author

Al-Mousawi, Ali and Mogensen, Trine Hyrup

Subjects
hemic and lymphatic diseases, COVID-19/complications, Humans, Child, Pandemics, Systemic Inflammatory Response Syndrome
Abstract

During the COVID-19 pandemic, the emergence of a new condition with hyperinflammatory shock, resembling Kawasaki disease (KD), was reported in children from Western countries strongly affected by SARS-CoV-2. This syndrome was termed paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS). Despite displaying features similar to KD, studies demonstrated a new and more severe disease entity with multiorgan involvement, in particular gastrointestinal symptoms and heart failure, with blood tests consistent with a postinfectious inflammatory condition as summarised in this review.

Published
2020

13. T cell-intrinsic C5L2 activation protects against uncontrolled inflammatory Th responses and autoimmunity

Author

West, Erin E, primary, Freeley, Simon, additional, Kolev, Martin, additional, Niyonzima, Nathalie, additional, Mogensen, Trine Hyrup, additional, Woodruff, Trent M, additional, Monk, Peter, additional, Lappegard, Knut, additional, Espevik, Terje, additional, Mollnes, Tom Eirik, additional, Christiansen, Mette, additional, and Kemper, Claudia, additional

Published
2020
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14. Severe capillary leak syndrome with cardiac arrest triggered by influenza virus infection

Author

Ebdrup, Lotte, Druey, Kirk M, Druey, Kirk, and Mogensen, Trine Hyrup

Subjects
medicine.medical_specialty, business.industry, Cardiogenic shock, Fulminant, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Capillary leak, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Heart failure, Internal medicine, medicine, Cardiology, Systemic capillary leak syndrome, 030212 general & internal medicine, business, Capillary Leak Syndrome, Rare disease
Abstract

Systemic capillary leak syndrome (SCLS), also known as Clarkson syndrome, is a rare disease with potential fatal outcome. The clinical picture involves leakage of fluid and protein from the bloodstream into peripheral tissues, resulting in hypoalbuminaemia, elevated haematocrit, oedema and hypotension. The spectrum of the symptoms ranges from discrete swelling/oedema of extremities to fulminant cardiogenic shock. We present a case with a 52-year-old man diagnosed with SCLS after being resuscitated from cardiac arrest, which was complicated by compartment syndrome. The severe episode of capillary leak was potentially triggered by influenza virus infection. With the benefit of hindsight, he presented with symptoms of SCLS 2 years prior the major acute episode. Here we describe this case and review some aspects of the literature on SCLS, with particular focus on the pathogenesis, treatment/prophylaxis and long-term physical and psychological complications.

Published
2018
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16. Herpes simplex encephalitis

Author

Jørgensen, Laura Krogh and Mogensen, Trine Hyrup

Abstract

Herpes simplex encephalitis (HSE) is a rare disease, although it is the most common form of sporadic encephalitis worldwide. Recently, studies have provided important new insight into the genetic and immunological basis of HSE. However, even in the presence of antiviral treatment, mortality and morbidity remain relatively high. Therefore, precise and early diagnosis together with basic and clinical studies to gain better insight into the pathogenesis of HSE is a prerequisite for the development of improved prophylaxis and treatment of this severe disease.

Published
2017

17. Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry

Author

Jørgensen,Laura Krogh, Dalgaard,Lars, Østergaard,Lars Jørgen, Andersen,Nanna Skaarup, Nørgaard,Mette, Mogensen,Trine Hyrup, Jørgensen,Laura Krogh, Dalgaard,Lars, Østergaard,Lars Jørgen, Andersen,Nanna Skaarup, Nørgaard,Mette, and Mogensen,Trine Hyrup

Abstract

Laura Krogh Jørgensen,1 Lars Skov Dalgaard,1 Lars Jørgen Østergaard,1 Nanna Skaarup Andersen,2 Mette Nørgaard,3 Trine Hyrup Mogensen1 1Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 2Department of Clinical Microbiology, Odense University Hospital, Odense, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR). Methods: The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10), from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV) of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we estimated the proportion of HSE cases coded with nonspecific ICD-10 codes of viral encephalitis and also the sensitivity of the HSE diagnosis coding. Results: We were able to validate 398 (94.3%) of the 422 HSE diagnoses identified via the DNPR. Hereof, 202 (50.8%) were classified as confirmed cases and 29 (7.3%) as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0–62.9). For “Encephalitis due to herpes simplex virus” (ICD-10 code B00.4), the PPV was 56.6% (95% CI: 51.1–62.0). Similarly, the PPV for “Meningoencephalitis due to herpes simplex virus” (ICD-10 code B00.4A) was 56.8% (

Published
2016

20. Human SNORA31variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis

Author

Lafaille, Fabien G., Harschnitz, Oliver, Lee, Yoon Seung, Zhang, Peng, Hasek, Mary L., Kerner, Gaspard, Itan, Yuval, Ewaleifoh, Osefame, Rapaport, Franck, Carlile, Thomas M., Carter-Timofte, Madalina E., Paquet, Dominik, Dobbs, Kerry, Zimmer, Bastian, Gao, Daxing, Rojas-Duran, Maria F., Kwart, Dylan, Rattina, Vimel, Ciancanelli, Michael J., McAlpine, Jessica L., Lorenzo, Lazaro, Boucherit, Soraya, Rozenberg, Flore, Halwani, Rabih, Henry, Benoit, Amenzoui, Naima, Alsum, Zobaida, Marques, Laura, Church, Joseph A., Al-Muhsen, Saleh, Tardieu, Marc, Bousfiha, Ahmed Aziz, Paludan, Søren R., Mogensen, Trine Hyrup, Quintana-Murci, Lluis, Tessier-Lavigne, Marc, Smith, Gregory A., Notarangelo, Luigi D., Studer, Lorenz, Gilbert, Wendy, Abel, Laurent, Casanova, Jean-Laurent, and Zhang, Shen-Ying

Abstract

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively. We report five unrelated patients with forebrain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA of the H/ACA class that are predicted to direct the isomerization of uridine residues to pseudouridine in small nuclear RNA and ribosomal RNA. We show that CRISPR/Cas9-introduced bi- and monoallelic SNORA31deletions render human pluripotent stem cell (hPSC)-derived cortical neurons susceptible to HSV-1. Accordingly, SNORA31-mutated patient hPSC-derived cortical neurons are susceptible to HSV-1, like those from TLR3- or STAT1-deficient patients. Exogenous interferon (IFN)-β renders SNORA31- and TLR3- but not STAT1-mutated neurons resistant to HSV-1. Finally, transcriptome analysis of SNORA31-mutated neurons revealed normal responses to TLR3 and IFN-α/β stimulation but abnormal responses to HSV-1. Human SNORA31thus controls central nervous system neuron-intrinsic immunity to HSV-1 by a distinctive mechanism.

Published
2019
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21. Infektionssygdomme

Author

Larsen, Carsten Schade, Arildsen, Hanne, Benfield, Thomas, Larsen, Helle Kiellberg, Laursen, Alex Lund, Leutscher, Peter Derek Christian, Mogensen, Trine Hyrup, Ovesen, Therese, Wejse, Christian, Bladbjerg, Else Marie, Sandbæk, Annelli, and Stallknect, Bente Merete

Published
2012

22. [Genetics and immunology behind herpes simplex encephalitis].

Author

Wiggers I and Mogensen TH

Subjects
Humans, Encephalitis, Herpes Simplex genetics
Abstract

Herpes simplex encephalitis is a devastating neurological disorder with a poor prognosis. For years, it remained elusive why a fraction of otherwise healthy individuals presented with the condition; this lack of insight has hampered understanding of disease pathogenesis and the development of novel effective therapies. However, recent studies have shown that the lack of viral containment can be caused by functionally related monogenic inborn errors of immunity at least in a subset of patients. This knowledge renders prophylactic measures and design of targeted therapies possible, as argued in this review.

Published
2022

23. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

Author

Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martínez A, Yang R, Haljasmägi L, Migaud M, Särekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen L, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Mégarbane B, Triantafyllia V, Fekkar A, Heath J, Franco J, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte O, Zhang Y, Snow A, Holland S, Biggs C, Moncada-Vélez M, Arias A, Lorenzo L, Boucherit S, Anglicheau D, Planas A, Haerynck F, Duvlis S, Nussbaum R, Ozcelik T, Keles S, Bousfiha A, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarstrom Q, Hammarstrom L, Dupont A, Kurolap A, Metz C, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros L, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye S, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann N, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes L, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig M, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer A, Kennelly S, Bourke N, Halwani R, Sharif-Askari F, Dorgham K, Sallette J, Mehlal-Sedkaoui S, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh D, Erikstrup C, Condino-Neto A, Prando C, Bondarenko A, Spaan A, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton R, Mane S, Anderson M, Boisson B, Béziat V, Zhang SY, Andreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, deLamballerie X, Burdet C, Bouadma L, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen P, Rodríguez-Gallego C, Piemonti L, Notarangelo L, Su H, Kisand K, Okada S, Puel A, Jouanguy E, Rice C, Tiberghien P, Zhang Q, Casanova JL, Abel L, and Cobat A

Abstract

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Published
2022
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24. [Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2].

Author

Al-Mousawi A and Mogensen TH

Subjects
Child, Humans, Pandemics, COVID-19 complications, Systemic Inflammatory Response Syndrome
Abstract

During the COVID-19 pandemic, the emergence of a new condition with hyperinflammatory shock, resembling Kawasaki disease (KD), was reported in children from Western countries strongly affected by SARS-CoV-2. This syndrome was termed paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS). Despite displaying features similar to KD, studies demonstrated a new and more severe disease entity with multiorgan involvement, in particular gastrointestinal symptoms and heart failure, with blood tests consistent with a postinfectious inflammatory condition as summarised in this review.

Published
2020

26. [Herpes simplex encephalitis].

Author

Jørgensen LK and Mogensen TH

Subjects
Acyclovir administration & dosage, Acyclovir therapeutic use, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Humans, Interferon-alpha immunology, Interferon-beta immunology, Simplexvirus genetics, Simplexvirus immunology, Toll-Like Receptor 3 genetics, Toll-Like Receptor 3 immunology, Encephalitis, Herpes Simplex diagnosis, Encephalitis, Herpes Simplex drug therapy, Encephalitis, Herpes Simplex genetics, Encephalitis, Herpes Simplex immunology
Abstract

Herpes simplex encephalitis (HSE) is a rare disease, although it is the most common form of sporadic encephalitis worldwide. Recently, studies have provided important new insight into the genetic and immunological basis of HSE. However, even in the presence of antiviral treatment, mortality and morbidity remain relatively high. Therefore, precise and early diagnosis together with basic and clinical studies to gain better insight into the pathogenesis of HSE is a prerequisite for the development of improved prophylaxis and treatment of this severe disease.

Published
2017

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