Abstract: The world continues to contend with successive waves of coronavirus disease 2019 (COVID-19), fueled by the emergence of viral variants. At the same time, persistent, prolonged and often debilitating sequelae are increasingly recognized in convalescent individuals, named ‘post-COVID-19 syndrome’ or ‘long-haul COVID’. Clinical symptomatology includes fatigue, malaise, dyspnea, defects in memory and concentration and a variety of neuropsychiatric syndromes as the major manifestations, and several organ systems can be involved. The underlying pathophysiological mechanisms are poorly understood at present. This Review details organ-specific sequelae of post-COVID-19 syndromes and examines the underlying pathophysiological mechanisms available so far, elaborating on persistent inflammation, induced autoimmunity and putative viral reservoirs. Finally, we propose diagnostic strategies to better understand this heterogeneous disorder that continues to afflict millions of people worldwide. https://www.nature.com/articles/s41590-021-01104-y
The article refers to a study that has good controls - we have a thread on the study here Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection, 2021, Phetsouphanh et al
Viral persistence is one hypothesis discussed, and surely one that could be investigated fairly easily. They note that they found CoV-2 in the gastrointestinal tract of some individuals at 4 months, although these individuals didn't have Long Covid. It seems plausible that some ongoing host-virus interaction might result in ME/CFS symptoms. There have been suggestions of persistence in fatigue syndromes following Ebola, EBV, rickettsias, other tick borne diseases and more. As the authors suggest, longitudinal measurement of the persistence of viral reservoirs and correlating that with Long Covid symptoms could be very useful. That the various hypotheses are discussed in Nature seems promising - hopefully it will encourage more research.
I like that they noted that immune response profiling has to go beyond the old 'cytokine levels in peripheral blood' analysis. Tissues need to be studied and more detail recorded about the various immune cells. I also like the recognition in the article that Long Covid is an important problem to solve. The article finishes with some commentary about the NIH PASC initiative.
