Frontiers in Immunology (Mar 2023)

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

  • Lisa Hurler,
  • Ágnes Szilágyi,
  • Federica Mescia,
  • Federica Mescia,
  • Laura Bergamaschi,
  • Laura Bergamaschi,
  • Blanka Mező,
  • Blanka Mező,
  • György Sinkovits,
  • Marienn Réti,
  • Veronika Müller,
  • Zsolt Iványi,
  • János Gál,
  • László Gopcsa,
  • Péter Reményi,
  • Beáta Szathmáry,
  • Botond Lakatos,
  • János Szlávik,
  • Ilona Bobek,
  • Zita Z. Prohászka,
  • Zsolt Förhécz,
  • Dorottya Csuka,
  • Erika Kajdácsi,
  • László Cervenak,
  • Petra Kiszel,
  • Tamás Masszi,
  • István Vályi-Nagy,
  • Reinhard Würzner,
  • Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration,
  • Paul A. Lyons,
  • Paul A. Lyons,
  • Erik J. M. Toonen,
  • Zoltán Prohászka,
  • Zoltán Prohászka,
  • Stephen Baker,
  • John R. Bradley,
  • Patrick F. Chinnery,
  • Daniel J. Cooper,
  • Gordon Dougan,
  • Ian G. Goodfellow,
  • Ravindra K. Gupta,
  • Nathalie Kingston,
  • Paul J. Lehner,
  • Paul A. Lyons,
  • Nicholas J. Matheson,
  • Caroline Saunders,
  • Kenneth G. C. Smith,
  • Charlotte Summers,
  • James Thaventhiran,
  • M. Estee Torok,
  • Mark R. Toshner,
  • Michael P. Weekes,
  • Gisele Alvio,
  • Sharon Baker,
  • Areti Bermperi,
  • Karen Brookes,
  • Ashlea Bucke,
  • Jo Calder,
  • Laura Canna,
  • Cherry Crucusio,
  • Isabel Cruz,
  • Rnalie de Jesus,
  • Katie Dempsey,
  • Giovanni Di Stephano,
  • Jason Domingo,
  • Anne Elmer,
  • Julie Harris,
  • Sarah Hewitt,
  • Heather Jones,
  • Sherly Jose,
  • Jane Kennet,
  • Yvonne King,
  • Jenny Kourampa,
  • Emily Li,
  • Caroline McMahon,
  • Anne Meadows,
  • Vivien Mendoza,
  • Criona O’Brien,
  • Charmain Ocaya,
  • Ciro Pascuale,
  • Marlyn Perales,
  • Jane Price,
  • Rebecca Rastall,
  • Carla Ribeiro,
  • Jane Rowlands,
  • Valentina Ruffolo,
  • Hugo Tordesillas,
  • Phoebe Vargas,
  • Bensi Vergese,
  • Laura Watson,
  • Jieniean Worsley,
  • Julie-Ann Zerrudo,
  • Laura Bergamaschi,
  • Ariana Betancourt,
  • Georgie Bower,
  • Ben Bullman,
  • Chiara Cossetti,
  • Aloka De Sa,
  • Benjamin J. Dunore,
  • Maddie Epping,
  • Stuart Fawke,
  • Stefan Gräf,
  • Richard Grenfell,
  • Andrew Hinch,
  • Josh Hodgson,
  • Christopher Huang,
  • Oisin Huhn,
  • Kelvin Hunter,
  • Isobel Jarvis,
  • Emma Jones,
  • Maša Josipović,
  • Ekaterina Legchenko,
  • Daniel Lewis,
  • Joe Marsden,
  • Jennifer Martin,
  • Federica Mescia,
  • Francesca Nice,
  • Ciara O’Donnell,
  • Ommar Omarjee,
  • Marianne Perera,
  • Linda Pointon,
  • Nicole Pond,
  • Nathan Richoz,
  • Nika Romashova,
  • Natalia Savoinykh,
  • Rahul Sharma,
  • Joy Shih,
  • Mateusz Strezlecki,
  • Rachel Sutcliffe,
  • Tobias Tilly,
  • Zhen Tong,
  • Carmen Treacy,
  • Lori Turner,
  • Jennifer Wood,
  • Marta Wylot,
  • John Allison,
  • Heather Biggs,
  • Helen Butcher,
  • Daniela Caputo,
  • Debbie Clapham-Riley,
  • Eleanor Dewhurst,
  • Christian Fernandez,
  • Anita Furlong,
  • Barbara Graves,
  • Jennifer Gray,
  • Tasmin Ivers,
  • Emma Le Gresley,
  • Rachel Linger,
  • Mary Kasanicki,
  • Sarah Meloy,
  • Francesca Muldoon,
  • Nigel Ovington,
  • Sofia Papadia,
  • Christopher J. Penkett,
  • Isabel Phelan,
  • Venkatesh Ranganath,
  • Jennifer Sambrook,
  • Katherine Schon,
  • Hannah Stark,
  • Kathleen E. Stirrups,
  • Paul Townsend,
  • Julie von Ziegenweidt,
  • Jennifer Webster,
  • Ali Asaripour,
  • Lucy Mwaura,
  • Caroline Patterson,
  • Gary Polwarth,
  • Katherine Bunclark,
  • Michael Mackay,
  • Alice Michael,
  • Sabrina Rossi,
  • Mayurun Selvan,
  • Sarah Spencer,
  • Cissy Yong,
  • Petra Polgarova

DOI
https://doi.org/10.3389/fimmu.2023.1162171
Journal volume & issue
Vol. 14

Abstract

Read online

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.

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