Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease
Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin Sidhu, Stephanie Ascough, Shona C. Moore, Noura Mohamed, J Nunag, Clara King, Olivia C. Leavy, Omer Elneima, Hamish McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria Harris, Linzy Houchen-Wolloff, Neil Greening, Nazir Lone, Matthew Thorpe, A. A. Roger Thompson, Sarah Rowland‐Jones, Annemarie B Docherty, James D. Chalmers, Ling‐Pei Ho, Alex Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Dan Wootton, Jennifer K. Quint, Thushan I. de Silva, Antonia Ho, Christopher Chiu, Ewen M. Harrison, William Greenhalf, J. Kenneth Baillie, Malcolm G. Semple, Lance Turtle, Rachael A Evans, Louise V. Wain, Christopher E. Brightling, Ryan S. Thwaites, Peter Openshaw, PHOSP-COVID collaborative group, Kathryn M. Abel, Huzaifa Adamali, Davies Adeloye, Oluwaseun Adeyemi, Rita Adrego, L A Aguilar Jimenez, Shanaz Ahmad, Nafees Haider, Rubina Ahmed, Nyarko Ahwireng, Mark Ainsworth, Asma Alamoudi, Mariam Ali, M Aljaroof, Louise Allan, Richard J. Allen, L. Allerton, Lynne Allsop, Ann Marie Allt, Paula Almeida, B Al-Sheklly, Danny Altmann, Maria Alvarez Corral, Shannon Amoils, David Anderson, Charalambos Antoniades, Gill Arbane, Ava Maria Arias, Chérie Armour, Lisa Armstrong, Natalie Armstrong, David Arnold, H Arnold, Abdul Ashish, Andrew Ashworth, M. Ashworth, Shahab Aslani, H Assefa-Kebede, Paul Atkin, Catherine Atkin, Raminder Aul, Hnin Aung, Liam Austin, Cristina Avram, Nikos Avramidis, A Ayoub, Marta Babores, Rhiannon R Baggott, J. Bagshaw, David Baguley
Abstract
. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.