Multiple early factors anticipate post-acute COVID-19 sequelae

Abstract

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 + T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Is It Useful to Question the Recovery Behaviour of Patients with ME/CFS or Long COVID?

“…The exertion intolerance and other ME/CFS symptoms might also be caused by virally induced autoimmunity [ 62 , 63 ]. Interestingly enough, similar mechanisms are also thought to play a part in the development of long COVID [ 64 , 65 , 66 ].…”

Early clues regarding the pathogenesis of long-COVID

“… Studies to date have identified certain factors that predict whether an individual with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will fully recover or develop post-acute sequelae, including the persistent symptoms that characterize long COVID. Shown here are several mechanisms with evidence supported by recent studies of individuals with post-acute sequelae of SARS-CoV-2 infection (PASC) [ 1 , 4. , 5.…”

“…The authors have no interests to declare. 1 Division of HIV, Infectious Diseases, and Global Medicine,…”

“…We can now expect the emergence of major scientific efforts addressing the pathogenesis of PASC. In one of the first systematic studies, a large collaborative group organized by the Institute for Systems Biology (Seattle, WA, USA) performed a longitudinal multi-omic systems biology analysis of over 200 individuals who were followed for 2–3 months after acute infection [ 1 ]. Several factors were associated with the development of PASC, including pre-existing diabetes mellitus, high-level SARS-CoV-2 viremia, and Epstein-Barr virus (EBV) reactivation during acute infection.…”

Lessons from Long COVID: working with patients to design better research

“…6 ). Also, having Long COVID is in itself associated with a weaker antibody response to infection and immune dysregulation [7][8][9] . Thus, it is not scientifically sound to use antibody testing to classify the exposure (past SARS-CoV-2 infection) in relation to the occurrence of the outcome (persistent symptoms), because the method used for classification itself may be causing the outcome if the aetiology of Long COVID is related to the nature of the immune response to the infection.…”