references.bib

@article{bastard,
	title = {Autoantibodies against type {I} {IFNs} in patients with life-threatening {COVID}-19},
	volume = {370},
	copyright = {Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/370/6515/eabd4585},
	doi = {10.1126/science.abd4585},
	abstract = {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
Structured Abstract
INTRODUCTIONInterindividual clinical variability is vast in humans infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from silent infection to rapid death. Three risk factors for life-threatening coronavirus disease 2019 (COVID-19) pneumonia have been identified—being male, being elderly, or having other medical conditions—but these risk factors cannot explain why critical disease remains relatively rare in any given epidemiological group. Given the rising toll of the COVID-19 pandemic in terms of morbidity and mortality, understanding the causes and mechanisms of life-threatening COVID-19 is crucial.
RATIONALEB cell autoimmune infectious phenocopies of three inborn errors of cytokine immunity exist, in which neutralizing autoantibodies (auto-Abs) against interferon-γ (IFN-γ) (mycobacterial disease), interleukin-6 (IL-6) (staphylococcal disease), and IL-17A and IL-17F (mucocutaneous candidiasis) mimic the clinical phenotypes of germline mutations of the genes that encode the corresponding cytokines or receptors. Human inborn errors of type I IFNs underlie severe viral respiratory diseases. Neutralizing auto-Abs against type I IFNs, which have been found in patients with a few underlying noninfectious conditions, have not been unequivocally shown to underlie severe viral infections. While searching for inborn errors of type I IFN immunity in patients with life-threatening COVID-19 pneumonia, we also tested the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical COVID-19. We searched for auto-Abs against type I IFNs in 987 patients hospitalized for life-threatening COVID-19 pneumonia, 663 asymptomatic or mildly affected individuals infected with SARS-CoV-2, and 1227 healthy controls from whom samples were collected before the COVID-19 pandemic.
RESULTSAt least 101 of 987 patients (10.2\%) with life-threatening COVID-19 pneumonia had neutralizing immunoglobulin G (IgG) auto-Abs against IFN-ω (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three individual type I IFNs. These auto-Abs neutralize high concentrations of the corresponding type I IFNs, including their ability to block SARS-CoV-2 infection in vitro. Moreover, all of the patients tested had low or undetectable serum IFN-α levels during acute disease. These auto-Abs were present before infection in the patients tested and were absent from 663 individuals with asymptomatic or mild SARS-CoV-2 infection (P {\textless} 10−16). They were present in only 4 of 1227 (0.33\%) healthy individuals (P {\textless} 10−16) before the pandemic. The patients with auto-Abs were 25 to 87 years old (half were over 65) and of various ancestries. Notably, 95 of the 101 patients with auto-Abs were men (94\%).
CONCLUSIONA B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6\% of women and 12.5\% of men. In these patients, adaptive autoimmunity impairs innate and intrinsic antiviral immunity. These findings provide a first explanation for the excess of men among patients with life-threatening COVID-19 and the increase in risk with age. They also provide a means of identifying individuals at risk of developing life-threatening COVID-19 and ensuring their enrolment in vaccine trials. Finally, they pave the way for prevention and treatment, including plasmapheresis, plasmablast depletion, and recombinant type I IFNs not targeted by the auto-Abs (e.g., IFN-β). {\textless}img class="fragment-image" aria-describedby="F1-caption" src="https://science.sciencemag.org/content/sci/370/6515/eabd4585/F1.medium.gif"/{\textgreater} Download high-res image Open in new tab Download Powerpoint Neutralizing auto-Abs to type I IFNs underlie life-threatening COVID-19 pneumonia.We tested the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical COVID-19 by impairing the binding of type I IFNs to their receptor and the activation of the downstream responsive pathway. Neutralizing auto-Abs are represented in red, and type I IFNs are represented in blue. In these patients, adaptive autoimmunity impairs innate and intrinsic antiviral immunity. ISGs, IFN-stimulated genes; TLR, Toll-like receptor; IFNAR, IFN-α/β receptor; pSTAT, phosphorylated signal transducers and activators of transcription; IRF, interferon regulatory factor.
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6\% of women and 12.5\% of men.
In a large immunological and genomics study of COVID-19 patients, autoantibodies to type 1 interferons correlated with outcomes.
In a large immunological and genomics study of COVID-19 patients, autoantibodies to type 1 interferons correlated with outcomes.},
	language = {en},
	number = {6515},
	urldate = {2021-05-09},
	journal = {Science},
	author = {Bastard, Paul and Rosen, Lindsey B. and Zhang, Qian and Michailidis, Eleftherios and Hoffmann, Hans-Heinrich and Zhang, Yu and Dorgham, Karim and Philippot, Quentin and Rosain, Jérémie and Béziat, Vivien and Manry, Jérémy and Shaw, Elana and Haljasmägi, Liis and Peterson, Pärt and Lorenzo, Lazaro and Bizien, Lucy and Trouillet-Assant, Sophie and Dobbs, Kerry and Jesus, Adriana Almeida de and Belot, Alexandre and Kallaste, Anne and Catherinot, Emilie and Tandjaoui-Lambiotte, Yacine and Pen, Jeremie Le and Kerner, Gaspard and Bigio, Benedetta and Seeleuthner, Yoann and Yang, Rui and Bolze, Alexandre and Spaan, András N. and Delmonte, Ottavia M. and Abers, Michael S. and Aiuti, Alessandro and Casari, Giorgio and Lampasona, Vito and Piemonti, Lorenzo and Ciceri, Fabio and Bilguvar, Kaya and Lifton, Richard P. and Vasse, Marc and Smadja, David M. and Migaud, Mélanie and Hadjadj, Jérome and Terrier, Benjamin and Duffy, Darragh and Quintana-Murci, Lluis and Beek, Diederik van de and Roussel, Lucie and Vinh, Donald C. and Tangye, Stuart G. and Haerynck, Filomeen and Dalmau, David and Martinez-Picado, Javier and Brodin, Petter and Nussenzweig, Michel C. and Boisson-Dupuis, Stéphanie and Rodríguez-Gallego, Carlos and Vogt, Guillaume and Mogensen, Trine H. and Oler, Andrew J. and Gu, Jingwen and Burbelo, Peter D. and Cohen, Jeffrey I. and Biondi, Andrea and Bettini, Laura Rachele and D'Angio, Mariella and Bonfanti, Paolo and Rossignol, Patrick and Mayaux, Julien and Rieux-Laucat, Frédéric and Husebye, Eystein S. and Fusco, Francesca and Ursini, Matilde Valeria and Imberti, Luisa and Sottini, Alessandra and Paghera, Simone and Quiros-Roldan, Eugenia and Rossi, Camillo and Castagnoli, Riccardo and Montagna, Daniela and Licari, Amelia and Marseglia, Gian Luigi and Duval, Xavier and Ghosn, Jade and Lab§, Hgid and Group§, NIAID-USUHS Immune Response to COVID and Clinicians§, Covid and Clinicians§, Covid-Storm and Group§, Imagine COVID and Group§, French COVID Cohort Study and Consortium§, The Milieu Intérieur and Cohort§, CoV-Contact and Biobank§, Amsterdam UMC Covid-19 and Effort§, COVID Human Genetic and Tsang, John S. and Goldbach-Mansky, Raphaela and Kisand, Kai and Lionakis, Michail S. and Puel, Anne and Zhang, Shen-Ying and Holland, Steven M. and Gorochov, Guy and Jouanguy, Emmanuelle and Rice, Charles M. and Cobat, Aurélie and Notarangelo, Luigi D. and Abel, Laurent and Su, Helen C. and Casanova, Jean-Laurent},
	month = oct,
	year = {2020},
	pmid = {32972996},
	note = {Publisher: American Association for the Advancement of Science
Section: Research Article},
	file = {Full Text PDF:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\N95L6STX\\Bastard et al. - 2020 - Autoantibodies against type I IFNs in patients wit.pdf:application/pdf;Snapshot:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\MCJIYQUI\\eabd4585.html:text/html},
}

@article{lit_il23_csf2,
	title = {Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?},
	volume = {139},
	issn = {0340-6717, 1432-1203},
	shorttitle = {Autoantibodies against cytokines},
	url = {https://link.springer.com/10.1007/s00439-020-02180-0},
	doi = {10.1007/s00439-020-02180-0},
	abstract = {Abstract
            Anti-cytokine autoantibodies may cause immunodeficiency and have been recently recognized as ‘autoimmune phenocopies of primary immunodeficiencies’ and are found in particular, but not exclusively in adult patients. By blocking the cytokine’s biological function, patients with anti-cytokine autoantibodies may present with a similar clinical phenotype as the related inborn genetic disorders. So far, autoantibodies to interferon (IFN)-γ, GM-CSF, to a group of TH-17 cytokines and to IL-6 have been found to be causative or closely associated with susceptibility to infection. This review compares infectious diseases associated with anti-cytokine autoantibodies with primary immunodeficiencies affecting similar cytokines or related pathways.},
	language = {en},
	number = {6-7},
	urldate = {2021-05-22},
	journal = {Human Genetics},
	author = {Ku, Chen-Lung and Chi, Chih-Yu and von Bernuth, Horst and Doffinger, Rainer},
	month = jun,
	year = {2020},
	pages = {783--794},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\E3RJ5II2\\Ku et al. - 2020 - Autoantibodies against cytokines phenocopies of p.pdf:application/pdf},
}

@article{lit_il17_22,
	title = {Autoantibodies against {IL}-{17A}, {IL}-{17F}, and {IL}-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type {I}},
	volume = {207},
	issn = {1540-9538, 0022-1007},
	url = {https://rupress.org/jem/article/207/2/291/40841/Autoantibodies-against-IL17A-IL17F-and-IL22-in},
	doi = {10.1084/jem.20091983},
	abstract = {Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-γ, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1β, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-β, tumor necrosis factor [α], or transforming growth factor β). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.},
	language = {en},
	number = {2},
	urldate = {2021-05-22},
	journal = {Journal of Experimental Medicine},
	author = {Puel, Anne and Döffinger, Rainer and Natividad, Angels and Chrabieh, Maya and Barcenas-Morales, Gabriela and Picard, Capucine and Cobat, Aurélie and Ouachée-Chardin, Marie and Toulon, Antoine and Bustamante, Jacinta and Al-Muhsen, Saleh and Al-Owain, Mohammed and Arkwright, Peter D. and Costigan, Colm and McConnell, Vivienne and Cant, Andrew J. and Abinun, Mario and Polak, Michel and Bougnères, Pierre-François and Kumararatne, Dinakantha and Marodi, László and Nahum, Amit and Roifman, Chaim and Blanche, Stéphane and Fischer, Alain and Bodemer, Christine and Abel, Laurent and Lilic, Desa and Casanova, Jean-Laurent},
	month = feb,
	year = {2010},
	pages = {291--297},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\E8KXCYRW\\Puel et al. - 2010 - Autoantibodies against IL-17A, IL-17F, and IL-22 i.pdf:application/pdf},
}


@article{zhang_inborn_2020,
	title = {Inborn errors of type {I} {IFN} immunity in patients with life-threatening {COVID}-19},
	volume = {370},
	copyright = {Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/370/6515/eabd4570},
	doi = {10.1126/science.abd4570},
	abstract = {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
Structured Abstract
INTRODUCTIONClinical outcomes of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection range from silent infection to lethal coronavirus disease 2019 (COVID-19). Epidemiological studies have identified three risk factors for severe disease: being male, being elderly, and having other medical conditions. However, interindividual clinical variability remains huge in each demographic category. Discovering the root cause and detailed molecular, cellular, and tissue- and body-level mechanisms underlying life-threatening COVID-19 is of the utmost biological and medical importance.
RATIONALEWe established the COVID Human Genetic Effort (www.covidhge.com) to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance. We sequenced the exome or genome of 659 patients of various ancestries with life-threatening COVID-19 pneumonia and 534 subjects with asymptomatic or benign infection. We tested the specific hypothesis that inborn errors of Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity that underlie life-threatening influenza pneumonia also underlie life-threatening COVID-19 pneumonia. We considered three loci identified as mutated in patients with life-threatening influenza: TLR3, IRF7, and IRF9. We also considered 10 loci mutated in patients with other viral illnesses but directly connected to the three core genes conferring influenza susceptibility: TICAM1/TRIF, UNC93B1, TRAF3, TBK1, IRF3, and NEMO/IKBKG from the TLR3-dependent type I IFN induction pathway, and IFNAR1, IFNAR2, STAT1, and STAT2 from the IRF7- and IRF9-dependent type I IFN amplification pathway. Finally, we considered various modes of inheritance at these 13 loci.
RESULTSWe found an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency {\textless}0.001, at the 13 candidate loci in the 659 patients with life-threatening COVID-19 pneumonia relative to the 534 subjects with asymptomatic or benign infection (P = 0.01). Experimental tests for all 118 rare nonsynonymous variants (including both pLOF and other variants) of these 13 genes found in patients with critical disease identified 23 patients (3.5\%), aged 17 to 77 years, carrying 24 deleterious variants of eight genes. These variants underlie autosomal-recessive (AR) deficiencies (IRF7 and IFNAR1) and autosomal-dominant (AD) deficiencies (TLR3, UNC93B1, TICAM1, TBK1, IRF3, IRF7, IFNAR1, and IFNAR2) in four and 19 patients, respectively. These patients had never been hospitalized for other life-threatening viral illness. Plasmacytoid dendritic cells from IRF7-deficient patients produced no type I IFN on infection with SARS-CoV-2, and TLR3−/−, TLR3+/−, IRF7−/−, and IFNAR1−/− fibroblasts were susceptible to SARS-CoV-2 infection in vitro.
CONCLUSIONAt least 3.5\% of patients with life-threatening COVID-19 pneumonia had known (AR IRF7 and IFNAR1 deficiencies or AD TLR3, TICAM1, TBK1, and IRF3 deficiencies) or new (AD UNC93B1, IRF7, IFNAR1, and IFNAR2 deficiencies) genetic defects at eight of the 13 candidate loci involved in the TLR3- and IRF7-dependent induction and amplification of type I IFNs. This discovery reveals essential roles for both the double-stranded RNA sensor TLR3 and type I IFN cell-intrinsic immunity in the control of SARS-CoV-2 infection. Type I IFN administration may be of therapeutic benefit in selected patients, at least early in the course of SARS-CoV-2 infection. {\textless}img class="fragment-image" aria-describedby="F1-caption" src="https://science.sciencemag.org/content/sci/370/6515/eabd4570/F1.medium.gif"/{\textgreater} Download high-res image Open in new tab Download Powerpoint Inborn errors of TLR3- and IRF7-dependent type I IFN production and amplification underlie life-threatening COVID-19 pneumonia.Molecules in red are encoded by core genes, deleterious variants of which underlie critical influenza pneumonia with incomplete penetrance, and deleterious variants of genes encoding biochemically related molecules in blue underlie other viral illnesses. Molecules represented in bold are encoded by genes with variants that also underlie critical COVID-19 pneumonia.
Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5\%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
A large immunological and genomics study of COVID-19 patients reveals excess mutations in the type I IFN pathway.
A large immunological and genomics study of COVID-19 patients reveals excess mutations in the type I IFN pathway.},
	language = {en},
	number = {6515},
	urldate = {2021-02-03},
	journal = {Science},
	author = {Zhang, Qian and Bastard, Paul and Liu, Zhiyong and Pen, Jérémie Le and Moncada-Velez, Marcela and Chen, Jie and Ogishi, Masato and Sabli, Ira K. D. and Hodeib, Stephanie and Korol, Cecilia and Rosain, Jérémie and Bilguvar, Kaya and Ye, Junqiang and Bolze, Alexandre and Bigio, Benedetta and Yang, Rui and Arias, Andrés Augusto and Zhou, Qinhua and Zhang, Yu and Onodi, Fanny and Korniotis, Sarantis and Karpf, Léa and Philippot, Quentin and Chbihi, Marwa and Bonnet-Madin, Lucie and Dorgham, Karim and Smith, Nikaïa and Schneider, William M. and Razooky, Brandon S. and Hoffmann, Hans-Heinrich and Michailidis, Eleftherios and Moens, Leen and Han, Ji Eun and Lorenzo, Lazaro and Bizien, Lucy and Meade, Philip and Neehus, Anna-Lena and Ugurbil, Aileen Camille and Corneau, Aurélien and Kerner, Gaspard and Zhang, Peng and Rapaport, Franck and Seeleuthner, Yoann and Manry, Jeremy and Masson, Cecile and Schmitt, Yohann and Schlüter, Agatha and Voyer, Tom Le and Khan, Taushif and Li, Juan and Fellay, Jacques and Roussel, Lucie and Shahrooei, Mohammad and Alosaimi, Mohammed F. and Mansouri, Davood and Al-Saud, Haya and Al-Mulla, Fahd and Almourfi, Feras and Al-Muhsen, Saleh Zaid and Alsohime, Fahad and Turki, Saeed Al and Hasanato, Rana and Beek, Diederik van de and Biondi, Andrea and Bettini, Laura Rachele and D’Angio’, Mariella and Bonfanti, Paolo and Imberti, Luisa and Sottini, Alessandra and Paghera, Simone and Quiros-Roldan, Eugenia and Rossi, Camillo and Oler, Andrew J. and Tompkins, Miranda F. and Alba, Camille and Vandernoot, Isabelle and Goffard, Jean-Christophe and Smits, Guillaume and Migeotte, Isabelle and Haerynck, Filomeen and Soler-Palacin, Pere and Martin-Nalda, Andrea and Colobran, Roger and Morange, Pierre-Emmanuel and Keles, Sevgi and Çölkesen, Fatma and Ozcelik, Tayfun and Yasar, Kadriye Kart and Senoglu, Sevtap and Karabela, Şemsi Nur and Rodríguez-Gallego, Carlos and Novelli, Giuseppe and Hraiech, Sami and Tandjaoui-Lambiotte, Yacine and Duval, Xavier and Laouénan, Cédric and Clinicians†, Covid-Storm and Clinicians†, Covid and Group†, Imagine COVID and Group†, French COVID Cohort Study and Cohort†, CoV-Contact and Biobank†, Amsterdam UMC Covid-19 and Effort†, COVID Human Genetic and Group†, NIAID-USUHS/TAGC COVID Immunity and Snow, Andrew L. and Dalgard, Clifton L. and Milner, Joshua D. and Vinh, Donald C. and Mogensen, Trine H. and Marr, Nico and Spaan, András N. and Boisson, Bertrand and Boisson-Dupuis, Stéphanie and Bustamante, Jacinta and Puel, Anne and Ciancanelli, Michael J. and Meyts, Isabelle and Maniatis, Tom and Soumelis, Vassili and Amara, Ali and Nussenzweig, Michel and García-Sastre, Adolfo and Krammer, Florian and Pujol, Aurora and Duffy, Darragh and Lifton, Richard P. and Zhang, Shen-Ying and Gorochov, Guy and Béziat, Vivien and Jouanguy, Emmanuelle and Sancho-Shimizu, Vanessa and Rice, Charles M. and Abel, Laurent and Notarangelo, Luigi D. and Cobat, Aurélie and Su, Helen C. and Casanova, Jean-Laurent},
	month = oct,
	year = {2020},
	pmid = {32972995},
	note = {Publisher: American Association for the Advancement of Science
Section: Research Article},
	file = {Full Text PDF:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\BHRYNCWF\\Zhang et al. - 2020 - Inborn errors of type I IFN immunity in patients w.pdf:application/pdf;Snapshot:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\HJYGU8WY\\eabd4570.html:text/html},
}


@article{long_covid,
	title = {Long {COVID}: an estrogen-associated autoimmune disease?},
	volume = {7},
	issn = {2058-7716},
	shorttitle = {Long {COVID}},
	url = {http://www.nature.com/articles/s41420-021-00464-6},
	doi = {10.1038/s41420-021-00464-6},
	language = {en},
	number = {1},
	urldate = {2021-05-31},
	journal = {Cell Death Discovery},
	author = {{The Long Covid Kids study group} and Ortona, Elena and Buonsenso, Danilo and Carfi, Angelo and Malorni, Walter},
	month = jun,
	year = {2021},
	pages = {77},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\R9MBPK9Q\\The Long Covid Kids study group et al. - 2021 - Long COVID an estrogen-associated autoimmune dise.pdf:application/pdf},
}



@article{aa_driving_severe_covid,
	title = {Rogue antibodies could be driving severe {COVID}-19},
	volume = {590},
	issn = {0028-0836, 1476-4687},
	url = {http://www.nature.com/articles/d41586-021-00149-1},
	doi = {10.1038/d41586-021-00149-1},
	language = {en},
	number = {7844},
	urldate = {2021-05-31},
	journal = {Nature},
	author = {Khamsi, Roxanne},
	month = feb,
	year = {2021},
	pages = {29--31},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\4K6C4BZ9\\Khamsi - 2021 - Rogue antibodies could be driving severe COVID-19.pdf:application/pdf},
}



@techreport{new_aa_covid,
	type = {preprint},
	title = {New-{Onset} {IgG} {Autoantibodies} in {Hospitalized} {Patients} with {COVID}-19},
	url = {http://medrxiv.org/lookup/doi/10.1101/2021.01.27.21250559},
	abstract = {Abstract
          
            Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50\% of patients, but in {\textless}15\% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis, systemic sclerosis and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in ∼25\% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 (ACE-2). A subset of autoantibodies and ACA developed
            de novo
            following SARS-CoV-2 infection while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 (NSP1) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.},
	language = {en},
	urldate = {2021-05-31},
	institution = {Allergy and Immunology},
	author = {Chang, Sarah Esther and Feng, Allan and Meng, Wenzhao and Apostolidis, Sokratis A. and Mack, Elisabeth and Artandi, Maja and Barman, Linda and Bennett, Kate and Chakraborty, Saborni and Chang, Iris and Cheung, Peggie and Chinthrajah, Sharon and Dhingra, Shaurya and Do, Evan and Finck, Amanda and Gaano, Andrew and Geßner, Reinhard and Giannini, Heather M. and Gonzalez, Joyce and Greib, Sarah and Gündisch, Margrit and Hsu, Alex Ren and Kuo, Alex and Manohar, Monali and Mao, Rong and Neeli, Indira and Neubauer, Andreas and Oniyide, Oluwatosin and Powell, Abigail Elizabeth and Puri, Rajan and Renz, Harald and Schapiro, Jeffrey M. and Weidenbacher, Payton A and Wittman, Rich and Ahuja, Neera and Chung, Ho-Ryun and Jagannathan, Pras and James, Judith and Kim, Peter S. and Meyer, Nuala J. and Nadeau, Kari and Radic, Marko and Robinson, William H. and Singh, Upinder and Wang, Taia T. and Wherry, E. John and Skevaki, Chrysanthi and Prak, Eline T. Luning and Utz, Pj},
	month = jan,
	year = {2021},
	doi = {10.1101/2021.01.27.21250559},
}


@incollection{aa_csf,
	address = {New York, NY},
	title = {Array-{Based} {Profiling} of {Proteins} and {Autoantibody} {Repertoires} in {CSF}},
	volume = {2044},
	isbn = {978-1-4939-9705-3 978-1-4939-9706-0},
	url = {http://link.springer.com/10.1007/978-1-4939-9706-0_19},
	language = {en},
	urldate = {2021-05-27},
	booktitle = {Cerebrospinal {Fluid} ({CSF}) {Proteomics}},
	publisher = {Springer New York},
	author = {Pin, Elisa and Sjöberg, Ronald and Andersson, Eni and Hellström, Cecilia and Olofsson, Jennie and Jernbom Falk, August and Bergström, Sofia and Remnestål, Julia and Just, David and Nilsson, Peter and Månberg, Anna},
	editor = {Santamaría, Enrique and Fernández-Irigoyen, Joaquín},
	year = {2019},
	doi = {10.1007/978-1-4939-9706-0_19},
	note = {Series Title: Methods in Molecular Biology},
	pages = {303--318},
}


@article{ifn,
	title = {The interferon system: an overview},
	volume = {6},
	issn = {10903798},
	shorttitle = {The interferon system},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1090379802905738},
	doi = {10.1053/ejpn.2002.0573},
	language = {en},
	urldate = {2021-05-25},
	journal = {European Journal of Paediatric Neurology},
	author = {De Andrea, Marco and Ravera, Raffaella and Gioia, Daniela and Gariglio, Marisa and Landolfo, Santo},
	month = may,
	year = {2002},
	pages = {A41--A46},
}


@misc{xmap,
	title = {{xMAP} {Cookbook}, {A} collection of methods and protocols for developing multiplex assays with {xMAP} technology},
	url = {https://cdn2.hubspot.net/hub/128032/file-213083097-pdf/Luminex-xMap_Cookbook.pdf},
	urldate = {2021-05-25},
	publisher = {Luminex},
	author = {{Stephen Angeloni,} and {Robert Cordes, Sherry Dunbar,} and {Carlos Garcia,} and {Grant Gibson,} and {Charles Martin,} and {Valerie Stone}},
	month = jul,
	year = {2013},
	note = {BR\_574.01\_0613},
}


@misc{fohm,
	title = {Bekräftade fall i {Sverige} – daglig uppdatering},
	url = {https://www.folkhalsomyndigheten.se/smittskydd-beredskap/utbrott/aktuella-utbrott/covid-19/statistik-och-analyser/bekraftade-fall-i-sverige/},
	urldate = {2021-05-25},
	author = {{Folkhälsomyndigheten}},
	month = may,
	year = {2021},
	file = {FOHM Covid-19:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\Y7AZDHDF\\09f821667ce64bf7be6f9f87457ed9aa.html:text/html},
}

@techreport{who_report,
	title = {Weekly {Operational} {Update} on {COVID}-19, {Issue} {No}. 56},
	url = {https://www.who.int/publications/m/item/weekly-operational-update-on-covid-19---24-may-2021},
	urldate = {2021-05-25},
	institution = {Word Health Organization},
	month = may,
	year = {2021},
}


@article{dysregulated,
	title = {Immunology, immunopathogenesis and immunotherapeutics of {COVID}-19; an overview},
	volume = {93},
	issn = {1567-5769},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784533/},
	doi = {10.1016/j.intimp.2020.107364},
	abstract = {•
              COVID-19 has a higher severity rate in patient’s diminished immune activity.
            
            
              •
              COVID-19 organ damage is associated with systemic inflammation and CRS.
            
            
              •
              COVID-19 immunotherapy demands perception of SARS-CoV-2 immune system interactions.
            
            
              •
              Findings demonstrated the profound nature of COVID-19 immune dysregulation.
            
            
              •
              Immunotherapies for COVID-19 is evolving, at least until a vaccine becomes available.
            
          
        , Coronavirus disease 2019 (COVID-19) infection which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a “public health emergency of international concern” (PHEIC). The infection is highly contagious, has a high mortality rate, and its pathophysiology remains poorly understood. Pulmonary inflammation with substantial lung damage together with generalized immune dysregulation are major components of COVID-19 pathogenesis. The former component, lung damage, seems to be at least in part a consequence of immune dysregulation. Indeed, studies have revealed that immune alteration is not merely an association, as it might occur in systemic infections, but, very likely, the core pathogenic element of COVID-19. In addition, precise management of immune response in COVID-19, i.e. enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. Herein, we have reviewed current evidence related to different aspects of COVID-19 immunology, including innate and adaptive immune responses against the virus and mechanisms of virus-induced immune dysregulation. Considering that current antiviral therapies are chiefly experimental, strategies to do immunotherapy for the management of disease have also been reviewed. Understanding immunology of COVID-19 is important in developing effective therapies as well as diagnostic, and prophylactic strategies for this disease.},
	urldate = {2021-02-03},
	journal = {International Immunopharmacology},
	author = {Mohamed Khosroshahi, Leila and Rokni, Mohsen and Mokhtari, Tahmineh and Noorbakhsh, Farshid},
	month = apr,
	year = {2021},
	pmid = {33486333},
	pmcid = {PMC7784533},
	pages = {107364},
	file = {PubMed Central Full Text PDF:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\C8XVWP3H\\Mohamed Khosroshahi et al. - 2021 - Immunology, immunopathogenesis and immunotherapeut.pdf:application/pdf},
}


@article{susceptibility,
	title = {Susceptibility to severe {COVID}-19},
	volume = {370},
	copyright = {Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License.},
	issn = {0036-8075, 1095-9203},
	url = {https://science.sciencemag.org/content/370/6515/404},
	doi = {10.1126/science.abe7591},
	abstract = {Genetic variants and autoantibodies that suppress antiviral immunity are linked to severe COVID-19
Genetic variants and autoantibodies that suppress antiviral immunity are linked to severe COVID-19},
	language = {en},
	number = {6515},
	urldate = {2021-02-03},
	journal = {Science},
	author = {Beck, David B. and Aksentijevich, Ivona},
	month = oct,
	year = {2020},
	pmid = {33093097},
	note = {Publisher: American Association for the Advancement of Science
Section: Perspective},
	pages = {404--405},
	file = {Full Text PDF:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\MSGYRDQN\\Beck and Aksentijevich - 2020 - Susceptibility to severe COVID-19.pdf:application/pdf;Snapshot:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\YDX3RJAP\\404.html:text/html},
}


@article{lit_il6,
	title = {Interleukin-6 and severe {COVID}-19: a systematic review and meta-analysis},
	volume = {31},
	issn = {1148-5493},
	shorttitle = {Interleukin-6 and severe {COVID}-19},
	url = {http://www.john-libbey-eurotext.fr/medline.md?doi=10.1684/ecn.2020.0448},
	doi = {10.1684/ecn.2020.0448},
	number = {2},
	urldate = {2021-05-22},
	journal = {European Cytokine Network},
	author = {Mojtabavi, Helia and Saghazadeh, Amene and Rezaei, Nima},
	month = jun,
	year = {2020},
	pages = {44--49},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\D6K2NKEU\\Mojtabavi et al. - 2020 - Interleukin-6 and severe COVID-19 a systematic re.pdf:application/pdf},
}

@article{lit_ifng,
    author = {Döffinger, Rainer and Helbert, Matthew R. and Barcenas-Morales, Gabriela and Yang, Kun and Dupuis, Stephanie and Ceron-Gutierrez, Lourdes and Espitia-Pinzon, Clara and Barnes, Neil and Bothamley, Graham and Casanova, Jean-Laurent and Longhurst, Hilary J. and Kumararatne, Dinakantha S.},
    title = "{Autoantibodies to Interferon-γ in a Patient with Selective Susceptibility to Mycobacterial Infection and Organ-Specific Autoimmunity}",
    journal = {Clinical Infectious Diseases},
    volume = {38},
    number = {1},
    pages = {e10-e14},
    year = {2004},
    month = {01},
    abstract = "{We evaluated a patient with disseminated Mycobacterium tuberculosis and Mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. His serum contained a high titer of immunoglobulin G autoantibody to interferon-γ (IFN-γ) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-γ can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.}",
    issn = {1058-4838},
    doi = {10.1086/380453},
    url = {https://doi.org/10.1086/380453},
    eprint = {https://academic.oup.com/cid/article-pdf/38/1/e10/1022112/38-1-e10.pdf},
}

@article{hif,
title = {Hypoxia-Inducible Factors in Physiology and Medicine},
journal = {Cell},
volume = {148},
number = {3},
pages = {399-408},
year = {2012},
issn = {0092-8674},
doi = {https://doi.org/10.1016/j.cell.2012.01.021},
url = {https://www.sciencedirect.com/science/article/pii/S0092867412000876},
author = {Gregg L. Semenza},
abstract = {Oxygen homeostasis represents an organizing principle for understanding metazoan evolution, development, physiology, and pathobiology. The hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis in all metazoan species. Rapid progress is being made in elucidating homeostatic roles of HIFs in many physiological systems, determining pathological consequences of HIF dysregulation in chronic diseases, and investigating potential targeting of HIFs for therapeutic purposes.}
}

@article{il2ra,
title = {IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation},
journal = {Current Opinion in Immunology},
volume = {23},
number = {5},
pages = {598-604},
year = {2011},
note = {Special section: Cytokines/Immunogenetics and transplantation},
issn = {0952-7915},
doi = {https://doi.org/10.1016/j.coi.2011.08.003},
url = {https://www.sciencedirect.com/science/article/pii/S0952791511001063},
author = {Wei Liao and Jian-Xin Lin and Warren J Leonard},
abstract = {Interleukin-2 (IL-2) is a pleiotropic cytokine that drives T-cell growth, augments NK cytolytic activity, induces the differentiation of regulatory T cells, and mediates activation-induced cell death. Along with IL-4, IL-7, IL-9, IL-15, and IL-21, IL-2 shares the common cytokine receptor γ chain, γc, which is mutated in humans with X-linked severe combined immunodeficiency. Herein, we primarily focus on the recently discovered complex roles of IL-2 in broadly modulating T cells for T helper cell differentiation. IL-2 does not specify the type of Th differentiation that occurs; instead, IL-2 modulates expression of receptors for other cytokines and transcription factors, thereby either promoting or inhibiting cytokine cascades that correlate with each Th differentiation state. In this fashion, IL-2 can prime and potentially maintain Th1 and Th2 differentiation as well as expand such populations of cells, whereas it inhibits Th17 differentiation but also can expand Th17 cells.}
}

@ARTICLE{neutrophil_damage,
AUTHOR={Wang, Jun and Li, Qian and Yin, Yongmei and Zhang, Yingying and Cao, Yingying and Lin, Xiaoming and Huang, Lihua and Hoffmann, Daniel and Lu, Mengji and Qiu, Yuanwang},   
	 
TITLE={Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19},      
	
JOURNAL={Frontiers in Immunology},      
	
VOLUME={11},      

PAGES={2063},     
	
YEAR={2020},      
	  
URL={https://www.frontiersin.org/article/10.3389/fimmu.2020.02063},       
	
DOI={10.3389/fimmu.2020.02063},      
	
ISSN={1664-3224},   
   
ABSTRACT={Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19.Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF.Results: Neutrophilia occurred in 6 of 8 severe patients at 7–19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis.Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.}
}

@article{prest,
	title = {A whole-genome bioinformatics approach to selection of antigens for systematic antibody generation},
	volume = {8},
	issn = {1615-9861},
	url = {https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/pmic.200800203},
	doi = {https://doi.org/10.1002/pmic.200800203},
	abstract = {Here, we present an antigen selection strategy based on a whole-genome bioinformatics approach, which is facilitated by an interactive visualization tool displaying protein features from both public resources and in-house generated data. The web-based bioinformatics platform has been designed for selection of multiple, non-overlapping recombinant protein epitope signature tags by display of predicted information relevant for antigens, including domain- and epitope sized sequence similarities to other proteins, transmembrane regions and signal peptides. The visualization tool also displays shared and exclusive protein regions for genes with multiple splice variants. A genome-wide analysis demonstrates that antigens for approximately 80\% of the human protein-coding genes can be selected with this strategy.},
	language = {en},
	number = {14},
	urldate = {2021-05-19},
	journal = {PROTEOMICS},
	author = {Berglund, Lisa and Björling, Erik and Jonasson, Kalle and Rockberg, Johan and Fagerberg, Linn and Szigyarto, Cristina Al-Khalili and Sivertsson, Åsa and Uhlén, Mathias},
	year = {2008},
	note = {\_eprint: https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdf/10.1002/pmic.200800203},
	keywords = {Antibody generation, Antigen selection, Bioinformatics, Epitope, Sequence similarity},
	pages = {2832--2839},
	file = {Snapshot:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\HVULD6NK\\pmic.html:text/html},
}


@Manual{R,
    title = {R: A Language and Environment for Statistical Computing},
    author = {{R Core Team}},
    organization = {R Foundation for Statistical Computing},
    address = {Vienna, Austria},
    year = {2017},
    url = {https://www.R-project.org/},
}

@book{ggplot2,
	address = {New York},
	series = {Use {R}!},
	title = {Ggplot2: elegant graphics for data analysis},
	isbn = {978-0-387-98140-6},
	shorttitle = {Ggplot2},
	publisher = {Springer},
	author = {Wickham, Hadley},
	year = {2009},
	note = {OCLC: ocn382399721},
	keywords = {Datenanalyse, Graphic methods, Graphische Darstellung, Plot (Graphische Darstellung), R (Computer program language), R (Programm), Visualisierung},
	annote = {ggplot 2}
}

@article{GO,
	title = {Gene {Ontology}: tool for the unification of biology},
	volume = {25},
	issn = {1061-4036},
	shorttitle = {Gene {Ontology}},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037419/},
	doi = {10.1038/75556},
	abstract = {Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.},
	number = {1},
	urldate = {2021-04-27},
	journal = {Nature genetics},
	author = {Ashburner, Michael and Ball, Catherine A. and Blake, Judith A. and Botstein, David and Butler, Heather and Cherry, J. Michael and Davis, Allan P. and Dolinski, Kara and Dwight, Selina S. and Eppig, Janan T. and Harris, Midori A. and Hill, David P. and Issel-Tarver, Laurie and Kasarskis, Andrew and Lewis, Suzanna and Matese, John C. and Richardson, Joel E. and Ringwald, Martin and Rubin, Gerald M. and Sherlock, Gavin},
	month = may,
	year = {2000},
	pmid = {10802651},
	pmcid = {PMC3037419},
	pages = {25--29},
	file = {PubMed Central Full Text PDF:C\:\\Users\\Alfred\\Zotero\\storage\\3LCNNIXS\\Ashburner et al. - 2000 - Gene Ontology tool for the unification of biology.pdf:application/pdf}
}

@Article{tidyverse,
    title = {Welcome to the {tidyverse}},
    author = {Hadley Wickham and Mara Averick and Jennifer Bryan and Winston Chang and Lucy D'Agostino McGowan and Romain François and Garrett Grolemund and Alex Hayes and Lionel Henry and Jim Hester and Max Kuhn and Thomas Lin Pedersen and Evan Miller and Stephan Milton Bache and Kirill Müller and Jeroen Ooms and David Robinson and Dana Paige Seidel and Vitalie Spinu and Kohske Takahashi and Davis Vaughan and Claus Wilke and Kara Woo and Hiroaki Yutani},
    year = {2019},
    journal = {Journal of Open Source Software},
    volume = {4},
    number = {43},
    pages = {1686},
    doi = {10.21105/joss.01686},
}

@Article{limma,
    author = {Matthew E Ritchie and Belinda Phipson and Di Wu and Yifang Hu and Charity W Law and Wei Shi and Gordon K Smyth},
    title = {{limma} powers differential expression analyses for {RNA}-sequencing and microarray studies},
    journal = {Nucleic Acids Research},
    year = {2015},
    volume = {43},
    number = {7},
    pages = {e47},
    doi = {10.1093/nar/gkv007},
}

@Manual{ggbeeswarm,
title = {ggbeeswarm: Categorical Scatter (Violin Point) Plots},
author = {Erik Clarke and Scott Sherrill-Mix},
year = {2017},
note = {R package version 0.6.0},
url = {https://CRAN.R-project.org/package=ggbeeswarm},
}

@Manual{ggpubr,
title = {ggpubr: 'ggplot2' Based Publication Ready Plots},
author = {Alboukadel Kassambara},
year = {2020},
note = {R package version 0.4.0},
url = {https://CRAN.R-project.org/package=ggpubr},
}

@article{uniprot,
	title = {{UniProt}: the universal protein knowledgebase in 2021},
	volume = {49},
	issn = {0305-1048},
	shorttitle = {{UniProt}},
	url = {https://doi.org/10.1093/nar/gkaa1100},
	doi = {10.1093/nar/gkaa1100},
	abstract = {The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.},
	number = {D1},
	urldate = {2021-04-27},
	journal = {Nucleic Acids Research},
	author = {{The UniProt Consortium}},
	month = jan,
	year = {2021},
	pages = {D480--D489},
	file = {Full Text PDF:C\:\\Users\\Alfred\\Zotero\\storage\\APNVDLJF\\The UniProt Consortium - 2021 - UniProt the universal protein knowledgebase in 20.pdf:application/pdf;Snapshot:C\:\\Users\\Alfred\\Zotero\\storage\\EF5GNHA4\\6006196.html:text/html}
}

@article{aa_ms,
	title = {Autoantibody {Profiling} in {Multiple} {Sclerosis} {Using} {Arrays} of {Human} {Protein} {Fragments}},
	volume = {12},
	issn = {1535-9476, 1535-9484},
	url = {http://www.mcponline.org/lookup/doi/10.1074/mcp.M112.026757},
	doi = {10.1074/mcp.M112.026757},
	language = {en},
	number = {9},
	urldate = {2021-02-02},
	journal = {Molecular \& Cellular Proteomics},
	author = {Ayoglu, Burcu and Häggmark, Anna and Khademi, Mohsen and Olsson, Tomas and Uhlén, Mathias and Schwenk, Jochen M. and Nilsson, Peter},
	month = sep,
	year = {2013},
	pages = {2657--2672},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\VEI7L7DS\\Ayoglu et al. - 2013 - Autoantibody Profiling in Multiple Sclerosis Using.pdf:application/pdf},
}

@article{community,
	title = {{SARS}-{CoV}-2 exposure, symptoms and seroprevalence in healthcare workers in {Sweden}},
	volume = {11},
	issn = {2041-1723},
	url = {http://www.nature.com/articles/s41467-020-18848-0},
	doi = {10.1038/s41467-020-18848-0},
	abstract = {Abstract
            SARS-CoV-2 may pose an occupational health risk to healthcare workers. Here, we report the seroprevalence of SARS-CoV-2 antibodies, self-reported symptoms and occupational exposure to SARS-CoV-2 among healthcare workers at a large acute care hospital in Sweden. The seroprevalence of IgG antibodies against SARS-CoV-2 was 19.1\% among the 2149 healthcare workers recruited between April 14th and May 8th 2020, which was higher than the reported regional seroprevalence during the same time period. Symptoms associated with seroprevalence were anosmia (odds ratio (OR) 28.4, 95\% CI 20.6–39.5) and ageusia (OR 19.2, 95\% CI 14.3–26.1). Seroprevalence was also associated with patient contact (OR 2.9, 95\% CI 1.9–4.5) and covid-19 patient contact (OR 3.3, 95\% CI 2.2–5.3). These findings imply an occupational risk for SARS-CoV-2 infection among healthcare workers. Continued measures are warranted to assure healthcare workers safety and reduce transmission from healthcare workers to patients and to the community.},
	language = {en},
	number = {1},
	urldate = {2021-02-02},
	journal = {Nature Communications},
	author = {Rudberg, Ann-Sofie and Havervall, Sebastian and Månberg, Anna and Jernbom Falk, August and Aguilera, Katherina and Ng, Henry and Gabrielsson, Lena and Salomonsson, Ann-Christin and Hanke, Leo and Murrell, Ben and McInerney, Gerald and Olofsson, Jennie and Andersson, Eni and Hellström, Cecilia and Bayati, Shaghayegh and Bergström, Sofia and Pin, Elisa and Sjöberg, Ronald and Tegel, Hanna and Hedhammar, My and Phillipson, Mia and Nilsson, Peter and Hober, Sophia and Thålin, Charlotte},
	month = dec,
	year = {2020},
	pages = {5064},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\E8FRURGU\\Rudberg et al. - 2020 - SARS-CoV-2 exposure, symptoms and seroprevalence i.pdf:application/pdf},
}

@article{42k,
	title = {Exploration of high-density protein microarrays for antibody validation and autoimmunity profiling},
	volume = {33},
	issn = {18716784},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1871678415001545},
	doi = {10.1016/j.nbt.2015.09.002},
	language = {en},
	number = {5},
	urldate = {2021-02-02},
	journal = {New Biotechnology},
	author = {Sjöberg, Ronald and Mattsson, Cecilia and Andersson, Eni and Hellström, Cecilia and Uhlen, Mathias and Schwenk, Jochen M. and Ayoglu, Burcu and Nilsson, Peter},
	month = sep,
	year = {2016},
	pages = {582--592},
}

@article{hpa,
	title = {Tissue-based map of the human proteome},
	volume = {347},
	issn = {0036-8075, 1095-9203},
	url = {https://www.sciencemag.org/lookup/doi/10.1126/science.1260419},
	doi = {10.1126/science.1260419},
	language = {en},
	number = {6220},
	urldate = {2021-02-02},
	journal = {Science},
	author = {Uhlen, M. and Fagerberg, L. and Hallstrom, B. M. and Lindskog, C. and Oksvold, P. and Mardinoglu, A. and Sivertsson, A. and Kampf, C. and Sjostedt, E. and Asplund, A. and Olsson, I. and Edlund, K. and Lundberg, E. and Navani, S. and Szigyarto, C. A.-K. and Odeberg, J. and Djureinovic, D. and Takanen, J. O. and Hober, S. and Alm, T. and Edqvist, P.-H. and Berling, H. and Tegel, H. and Mulder, J. and Rockberg, J. and Nilsson, P. and Schwenk, J. M. and Hamsten, M. and von Feilitzen, K. and Forsberg, M. and Persson, L. and Johansson, F. and Zwahlen, M. and von Heijne, G. and Nielsen, J. and Ponten, F.},
	month = jan,
	year = {2015},
	pages = {1260419--1260419},
}

@article{aa_healthy,
	title = {Individual and stable autoantibody repertoires in healthy individuals},
	volume = {52},
	issn = {0891-6934, 1607-842X},
	url = {https://www.tandfonline.com/doi/full/10.1080/08916934.2019.1581774},
	doi = {10.1080/08916934.2019.1581774},
	language = {en},
	number = {1},
	urldate = {2021-02-02},
	journal = {Autoimmunity},
	author = {Neiman, Maja and Hellström, Cecilia and Just, David and Mattsson, Cecilia and Fagerberg, Linn and Schuppe-Koistinen, Ina and Gummesson, Anders and Bergström, Göran and Kallioniemi, Olli and Achour, Adnane and Sallinen, Riitta and Uhlén, Mathias and Nilsson, Peter},
	month = jan,
	year = {2019},
	pages = {1--11},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\9M6EREF3\\Neiman et al. - 2019 - Individual and stable autoantibody repertoires in .pdf:application/pdf},
}


@techreport{fas2,
	type = {preprint},
	title = {{SARS}-{CoV}-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild {COVID}-19 infection},
	url = {http://medrxiv.org/lookup/doi/10.1101/2021.01.03.21249162},
	abstract = {Abstract
          
            Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96\%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91\% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80\% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p=2*10
            −23
            and 2*10
            −13
            respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.},
	language = {en},
	urldate = {2021-04-28},
	institution = {Infectious Diseases (except HIV/AIDS)},
	author = {Havervall, Sebastian and Falk, August Jernbom and Klingström, Jonas and Ng, Henry and Greilert-Norin, Nina and Gabrielsson, Lena and Salomonsson, Ann-Christin and Isaksson, Eva and Rudberg, Ann-Sofie and Hellström, Cecilia and Andersson, Eni and Olofsson, Jennie and Skoglund, Lovisa and Yousef, Jamil and Pin, Elisa and Christ, Wanda and Olausson, Mikaela and Hedhammar, My and Tegel, Hanna and Mangsbo, Sara and Phillipson, Mia and Månberg, Anna and Hober, Sophia and Nilsson, Peter and Thålin, Charlotte},
	month = jan,
	year = {2021},
	doi = {10.1101/2021.01.03.21249162},
	file = {Submitted Version:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\SW8M9H45\\Havervall et al. - 2021 - SARS-CoV-2 induces a durable and antigen specific .pdf:application/pdf},
}


@article{ensembl,
	title = {Ensembl 2021},
	volume = {49},
	issn = {0305-1048, 1362-4962},
	url = {https://academic.oup.com/nar/article/49/D1/D884/5952199},
	doi = {10.1093/nar/gkaa942},
	abstract = {Abstract
            The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.},
	language = {en},
	number = {D1},
	urldate = {2021-05-06},
	journal = {Nucleic Acids Research},
	author = {Howe, Kevin L and Achuthan, Premanand and Allen, James and Allen, Jamie and Alvarez-Jarreta, Jorge and Amode, M Ridwan and Armean, Irina M and Azov, Andrey G and Bennett, Ruth and Bhai, Jyothish and Billis, Konstantinos and Boddu, Sanjay and Charkhchi, Mehrnaz and Cummins, Carla and Da Rin Fioretto, Luca and Davidson, Claire and Dodiya, Kamalkumar and El Houdaigui, Bilal and Fatima, Reham and Gall, Astrid and Garcia Giron, Carlos and Grego, Tiago and Guijarro-Clarke, Cristina and Haggerty, Leanne and Hemrom, Anmol and Hourlier, Thibaut and Izuogu, Osagie G and Juettemann, Thomas and Kaikala, Vinay and Kay, Mike and Lavidas, Ilias and Le, Tuan and Lemos, Diana and Gonzalez Martinez, Jose and Marugán, José Carlos and Maurel, Thomas and McMahon, Aoife C and Mohanan, Shamika and Moore, Benjamin and Muffato, Matthieu and Oheh, Denye N and Paraschas, Dimitrios and Parker, Anne and Parton, Andrew and Prosovetskaia, Irina and Sakthivel, Manoj P and Salam, Ahamed I Abdul and Schmitt, Bianca M and Schuilenburg, Helen and Sheppard, Dan and Steed, Emily and Szpak, Michal and Szuba, Marek and Taylor, Kieron and Thormann, Anja and Threadgold, Glen and Walts, Brandon and Winterbottom, Andrea and Chakiachvili, Marc and Chaubal, Ameya and De Silva, Nishadi and Flint, Bethany and Frankish, Adam and Hunt, Sarah E and IIsley, Garth R and Langridge, Nick and Loveland, Jane E and Martin, Fergal J and Mudge, Jonathan M and Morales, Joanella and Perry, Emily and Ruffier, Magali and Tate, John and Thybert, David and Trevanion, Stephen J and Cunningham, Fiona and Yates, Andrew D and Zerbino, Daniel R and Flicek, Paul},
	month = jan,
	year = {2021},
	pages = {D884--D891},
	file = {Full Text:C\:\\Users\\alfred.kedhammar\\Zotero\\storage\\C4CKJBDU\\Howe et al. - 2021 - Ensembl 2021.pdf:application/pdf},
}