Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2 2023 Yin et al

Abstract

Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple omics assays (CyTOF, RNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis.

Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses.

Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.

https://www.biorxiv.org/content/10.1101/2023.02.09.527892v1

 

Same authors as Long-term SARS-CoV-2-specific immune & inflammatory responses in individuals recovering from COVID-19 with & without post-acute symptoms (2021, Cell Reports)

 

See also Divergent adaptive immune responses define two types of Long COVID (2023) —

 

Preprint recently updated to v2, so possibly this is the version to be published.

Haven't re-read, but the abstract adds the following sentence: "RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC."

 

Now published as the Letter Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2 in Nature Immonology.

Haven't seen if there's new data compared to the preprints, but the reviewers wanted quite a few changes so perhaps there's something interesting that previously wasn't part of the data (according to the reviewers the following data was added:"confirmatory FACS experiments, scRNAseq evaluation of a subset of study participants as well as adjusted and expanded data analyses resulting in a substantial increase of supplementary figures") https://static-content.springer.com/esm/art:10.1038/s41590-023-01724-6/MediaObjects/41590_2023_1724_MOESM3_ESM.pdf.