IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition
Authors: Haslund-Gourley Benjamin S. , Woloszczuk Kyra , Hou Jintong , Connors Jennifer , Cusimano Gina , Bell Mathew , Taramangalam Bhavani , Fourati Slim , Mege Nathan , Bernui Mariana , Altman Matthew C. , Krammer Florian , van Bakel Harm ,   IMPACC Network,   IMPACC Steering Committee, Ozonoff Al , Ehrlich Lauren I. R. , Melamed Esther , Sesma Ana Fernandez , Simon Viviana , Pulendran Bali , Nadeau Kari C. , Davis Mark M. , McCoey Grace A. , Sekaly Rafick , Baden Lindsey R. , Levy Ofer , Schaenman Joanna , Reed Elaine F. , Shaw Albert C. , Hafler David A. , Montgomery Ruth R. , Kleinstein Steven H. , Becker Patrice M. , Augustine Alison D. , Calfee Carolyn S. , Erle David J. , DeBakey Michael E. , Corry David B. , Kheradmand Farrah , Atkinson Mark A. , Brakenridge Scott C. , Higuita Nelson I. Agudelo , Metcalf Jordan P. , Hough Catherine L. , Messer William B. , Kraft Monica , Bime Chris , Peters Bjoern ,   Clinical & Data Coordinating Center (CDCC), Milliren Carly E. , Syphurs Caitlin , McEnaney Kerry , Barton Brenda , Lentucci Claudia , Saluvan Mehmet , Chang Ana C. , Hoch Annmarie , Albert Marisa , Shaheen Tanzia , Kho Alvin T. , Liu Shanshan , Thomas Sanya , Chen Jing , Murphy Maimouna D. , Cooney Mitchell , Hayati Arash Nemati , Bryant Robert , Abraham James ,   IMPACC Data Analysis Group, Jayavelu Naresh Doni , Presnell Scott , Jancsyk Tomasz , Maguire Cole , Qi Jingjing , Lee Brian , Fourati Slim , Esserman Denise A. , Guan Leying , Gygi Jeremy , Pawar Shrikant , Brito Anderson , Fragiadakis Gabriela K. , Patel Ravi , Overton James A. , Vita Randi , Westendorf Kerstin , Shannon Casey P. , Tebbutt Scott J. ,   IMPACC Site Investigators, Thyagarajan Rama V. , Rousseau Justin F. , Wylie Dennis , Triplett Todd A. , Kojic Erna , Chinthrajah Sharon , Ahuja Neera , Rogers Angela J. , Artandi Maja , Geng Linda , Yendewa George , Powell Debra L. , Kim James N. , Simmons Brent , Goonewardene I. Michael , Smith Cecilia M. , Martens Mark , Sherman Amy C. , Walsh Stephen R. , Issa Nicolas C. , Salehi-Rad Ramin , Dela Cruz Charles , Farhadian Shelli , Iwasaki Akiko , Ko Albert I. , Anderson Evan J. , Mehta Aneesh K. , Sevransky Jonathan E. , Seyfert-Margolis Vicki , Leligdowicz Aleksandra , Matthay Michael A. , Singer Jonathan P. , Kangelaris Kirsten N. , Hendrickson Carolyn M. , Krummel Matthew F. , Langelier Charles R. , Woodruff Prescott G. , Corry David B. , Kheradmand Farrah , Anderson Matthew L. , Guirgis Faheem W. , Drevets Douglas A. , Brown Brent R. , Siegel Sarah A. R. , Lu Zhengchun , Mosier Jarrod , Kimura Hiroki ,   IMPACC Core Laboratory, Khor Bernard , van Bakel Harm , Rahman Adeeb , Stadlbauer Daniel , Dutta Jayeeta , Xie Hui , Kim-Schulze Seunghee , Gonzalez-Reiche Ana Silvia , van de Guchte Adriana , Carreño Juan Manuel , Singh Gagandeep , Raskin Ariel , Tcheou Johnstone , Bielak Dominika , Kawabata Hisaaki , Kelly Geoffrey , Patel Manishkumar , Nie Kai , Yellin Temima , Fried Miriam , Sullivan Leeba , Morris Sara , Sieg Scott , Steen Hanno , van Zalm Patrick , Fatou Benoit , Mendez Kevin , Lasky-Su Jessica , Hutton Scott R. , Michelotti Greg , Wong Kari , Jha Meenakshi , Viode Arthur , Kanarek Naama , Petrova Boryana , Zhao Yujiao , Bosinger Steven E. , Boddapati Arun K. , Tharp Greg K. , Pellegrini Kathryn L. , Beagle Elizabeth , Cowan David , Hamilton Sydney , Ribeiro Susan Pereira , Hodder Thomas , Rosen Lindsey B. , Lee Serena , Wilson Michael R. , Dandekar Ravi , Alvarenga Bonny , Rajan Jayant , Eckalbar Walter , Schroeder Andrew W. , Tsitsiklis Alexandra , Mick Eran , Guerrero Yanedth Sanchez , Love Christina , Maliskova Lenka , Adkisson Michael ,   IMPACC Clinical Study Team, Siles Nadia , Geltman Janelle , Hurley Kerin , Saksena Miti , Altman Deena , Srivastava Komal , Eaker Lily Q. , Bermúdez-González Maria C. , Beach Katherine F. , Sominsky Levy A. , Azad Arman R. , Mulder Lubbertus C. F. , Kleiner Giulio , Lee Alexandra S. , Do Evan , Fernandes Andrea , Manohar Monali , Hagan Thomas , Blish Catherine A. , Din Hena Naz , Roque Jonasel , Yang Samuel , Sigal Natalia , Chang Iris , Tribout Heather , Harris Paul , Consolo Mary , Edwards Carolyn , Lee Edward , Lin Edward , Croen Brett , Semenza Nicholas C. , Rogowski Brandon , Melnyk Nataliya , Bell Mathew R. , Furukawa Sara , McLin Renee , Schearer Pamela , Sheidy Julie , Tegos George P. , Nagle Crystal , Smolen Kinga , Desjardins Michael , van Haren Simon , Mitre Xhoi , Cauley Jessica , Li Xiaofang , Tong Alexandra , Evans Bethany , Montesano Christina , Licona Jose Humberto , Krauss Jonathan , Chang Jun Bai Park , Izaguirre Natalie , Rooks Rebecca , Elashoff David , Brook Jenny , Ramires-Sanchez Estefania , Llamas Megan , Rivera Adreanne , Perdomo Claudia , Ward Dawn C. , Magyar Clara E. , Fulcher Jennifer A. , Pickering Harry C. , Sen Subha , Chaudhary Omkar , Coppi Andreas , Fournier John , Mohanty Subhasis , Muenker Catherine , Nelson Allison , Raddassi Khadir , Rainone Michael , Ruff William E. , Salahuddin Syim , Schulz Wade L. , Vijayakumar Pavithra , Wang Haowei , Wunder Elsio , Young H. Patrick , Rothman Jessica , Konstorum Anna , Chen Ernie , Cotsapas Chris , Grubaugh Nathan D. , Wang Xiaomei , Xu Leqi , Asashima Hiromitsu , Bristow Laurel , Hussaini Laila , Hellmeister Kieffer , Samaha Hady , Wimalasena Sonia Tandon , Cheng Andrew , Spainhour Christine , Scherer Erin M. , Johnson Brandi , Bechnak Amer , Ciric Caroline R. , Hewitt Lauren , Carter Erin , Mcnair Nina , Panganiban Bernadine , Huerta Christopher , Usher Jacob , Vaysman Tatyana , Holland Steven M. , Abe-Jones Yumiko , Asthana Saurabh , Beagle Alexander , Bhide Sharvari , Carrillo Sidney A. , Chak Suzanna , Ghale Rajani , Gonzalez Ana , Jauregui Alejandra , Jones Norman , Lea Tasha , Lee Deanna , Lota Raphael , Milush Jeff , Nguyen Viet , Pierce Logan , Prasad Priya A. , Rao Arjun , Samad Bushra , Shaw Cole , Sigman Austin , Sinha Pratik , Ward Alyssa , Willmore Andrew , Zhan Jenny , Rashid Sadeed , Rodriguez Nicklaus , Tang Kevin , Altamirano Luz Torres , Betancourt Legna , Curiel Cindy , Sutter Nicole , Paz Maria Tercero , Tietje-Ulrich Gayelan , Leroux Carolyn , Thakur Neeta , Vasquez Joshua J. , Santhosh Lekshmi , Song Li-Zhen , Nelson Ebony , Moldawer Lyle L. , Borresen Brittany , Roth-Manning Brittney , Ungaro Ricardo F. , Oberhaus Jordan , Booth J. Leland , Sinko Lauren A. , Brunton Amanda , Sullivan Peter E. , Strnad Matthew , Lyski Zoe L. , Coulter Felicity J. , Micheleti Courtney , Conway Michelle , Francisco Dave , Molzahn Allyson , Erickson Heidi , Wilson Connie Cathleen , Schunk Ron , Sierra Bianca , Hughes Trina , Maecker Holden T. , Rouphael Nadine , Diray-Arce Joann , Wigdahl Brian , Kutzler Michele A. , Cairns Charles B. , Haddad Elias K. , Comunale Mary Ann 
Published: January 2024

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.