Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.
Creators: name: Liew, Felicity
name: Efstathiou, Claudia
name: Fontanella, Sara
name: Richardson, Matthew
name: Saunders, Ruth
name: Swieboda, Dawid
name: Sidhu, Jasmin K
name: Ascough, Stephanie
name: Moore, Shona C
name: Mohamed, Noura
name: Nunag, Jose
name: King, Clara
name: Leavy, Olivia C
name: Elneima, Omer
name: McAuley, Hamish JC
name: Shikotra, Aarti
name: Singapuri, Amisha
name: Sereno, Marco
name: Harris, Victoria C
name: Houchen-Wolloff, Linzy
name: Greening, Neil J
name: Lone, Nazir I
name: Thorpe, Matthew
name: Thompson, AA Roger
name: Rowland-Jones, Sarah L
name: Docherty, Annemarie B
name: Chalmers, James D
name: Ho, Ling-Pei
name: Horsley, Alexander
name: Raman, Betty
name: Poinasamy, Krisnah
name: Marks, Michael
name: Kon, Onn Min
name: Howard, Luke S
name: Wootton, Daniel G
name: Quint, Jennifer K
name: de Silva, Thushan I
name: Ho, Antonia
name: Chiu, Christopher
name: Harrison, Ewen M
name: Greenhalf, William
name: Baillie, J Kenneth
name: Semple, Malcolm G
name: Turtle, Lance
name: Evans, Rachael A
name: Wain, Louise V
name: Brightling, Christopher
name: Thwaites, Ryan S
name: Openshaw, Peter JM
name: group, PHOSP-COVID collaborative
name: investigators, ISARIC
Publisher: name: The Francis Crick Institute
Year: 2024
Subjects: classificationCode: Chemical Biology & High Throughput
subject: Chemical Biology &amp; High Throughput
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Infectious Disease
subject: Infectious Disease
classificationCode: Immunology
subject: Immunology
subject: FOS: Clinical medicine
classificationCode: Metabolism
subject: Metabolism
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Model organisms
subject: Model organisms
classificationCode: Synthetic Biology
subject: Synthetic Biology

description: One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. 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.