The ongoing COVID-19 pandemic has been accompanied by an influx of research probing the acute consequences of SARS-CoV-2 infection. Still, the long-term immunological impacts of this respiratory virus infection in patients recovered from asymptomatic or mild cases remain poorly understood. To investigate this, MIRC alumnus Dr. Allison Kennedy from the Bowdish lab and co-author Dr. Laura Cook analyzed the cytokines and leukocyte populations in the circulation of individuals recently recovered from mild COVID-19. Their study, published in Viruses, shows that these patients exhibit prolonged inflammation and leukocyte activation 1-3 months post infection, in contrast to other respiratory infections.
To investigate this immune dysregulation Kennedy et al. first quantified levels of inflammatory mediators, such as IL-6, TNF-α, and C-reactive protein (CRP) in sera collected at 1-3 or 6-9 months post-COVID and sera from COVID-seronegative individuals. Compared with those recently recovered from other mild respiratory infections, participants with previous mild SARS-CoV-2 infection showed elevated IL-6 and TNF-α at 1-3 months post-infection, while CRP was elevated at 1-3 and 6-9 months post-infection. Treatment of blood samples with the CytoStim superantigen reagent further revealed significantly higher activation of CD4+ and CD8+ T cells at 1-3 months post-infection for the COVID-19 seropositive group compared to participants that were seronegative. The proportion of activated CD4+ T cells was further correlated with elevated CRP levels, though the detail of this connection is not yet clear. Flow cytometry analysis further demonstrated post-COVID changes in monocyte migration and activation markers. At 1-3 months post-infection, monocyte CD11b expression was increased, indicating sustained cellular inflammation following SARS-CoV-2 infection.
This work by Dr. Kennedy contributes significantly to understanding the long-term consequences of mild and asymptomatic COVID-19. Following this pandemic, it is important to define the precise manner of immunological alterations that give way to the many faces of “long COVID”. Furthermore, these observations uncover SARS-CoV-2-induced dysregulation of immune activation and identify potential approaches for treatment of long COVID.
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