Immunological dysfunction persists 8 months from initial mild-moderate SARS-CoV-2 infection

  

View ORCID ProfileChansavath Phetsouphanh,  View ORCID ProfileDavid Darley, Daniel B Wilson, Annett Howe,  View ORCID ProfileC. Mee Ling Munier, Sheila K Patel,  View ORCID ProfileJennifer A Juno,  View ORCID ProfileLouise M Burrell, Stephen J Kent, Gregory J Dore, Anthony D Kelleher, Gail V Matthews

doi: https://doi.org/10.1101/2021.06.01.21257759

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.06.01.21257759v2.full.pdf

Abstract

A proportion of patients surviving acute COVID-19 infection develop post-COVID syndrome (long COVID) encompassing physical and neuropsychiatric symptoms lasting longer than 12 weeks. Here we studied a prospective cohort of individuals with long COVID compared to age/gender matched subjects without long COVID (from the ADAPT study), healthy donors and individuals infected with other non-SARS CoV2 human coronaviruses (the ADAPT-C study). We found highly activated innate immune cells and an absence of subsets of un-activated naïve T and B cells in peripheral blood of long COVID subjects, that did not reconstitute over time. These activated myeloid cells may contribute to the elevated levels of type I (IFN-β) and III interferon (IFN-λ1) that remained persistently high in long COVID subjects at 8 months post-infection. We found positive inter-analyte correlations that consisted of 18 inflammatory cytokines in symptomatic long COVID subjects that was not observed in asymptomatic COVID-19 survivors. A linear classification model was used to exhaustively search through all 20475 combinations of the 29 analytes measured, that had the strongest association with long COVID and found that the best 4 analytes were: IL-6, IFN-γ, MCP-1 (CCL2) and VCAM-1. These four inflammatory biomarkers gave an accuracy of 75.9%, and an F1 score of 0.759, and have also previously been associated with acute severe disease. In contrast, plasma ACE2 levels, while elevated in the serum of people previously infected with SARS-CoV-2 were not further elevated in subjects with long COVID symptoms. This work defines immunological parameters associated with long COVID and suggests future opportunities to prevention and treatment.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

ACTRN12620000554965

Funding Statement

We appreciate grant support from the St Vincents Clinic Foundation - the Curran Foundation, the Rapid Response Research Fund (UNSW) - the Medical Research Futures Fund (Australia) - NHMRC programme grant APP 1055214 (LMB) - Medical Research Future Fund award GNT 1175865 - - Austin Medical Research Foundation Grant - the Victorian Government - MRFF Award (2005544) - NHMRC program grant (1149990) - NHMRC Fellowships 1136322 and 1123673

https://www.medrxiv.org/content/10.1101/2021.06.01.21257759v2