Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

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Abstract

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC.

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  1. SciScore for 10.1101/2021.09.21.21263845: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Human Participants: All research was approved by the Emory University Institutional Review Board (Emory IRB nos.
    Consent: Informed consent was obtained from all participants or, if they were unable to provide informed consent, from designated healthcare surrogates
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Adults aged ≥18 years with documented SARS-CoV-2 antigen or anti-nucleocapsid antibody (64%), or those meeting the CDC COVID-19 clinical case definition who were experiencing new or worsening symptoms and were >14 days from COVID-19 onset (36%) were eligible.
    anti-nucleo…