Communications medicine · 2026
Divergent inflammatory and neurology-related protein levels in long COVID following primary and breakthrough SARS-CoV-2 infections.
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Bansal Amit, Olechnowicz Sam W Z, Kiernan-Walker Nicholas, Cumming Jacob, Abdul Azeez Imadh, Mazhari Ramin, COVID PROFILE consortium, Cox Rebecca J, Mueller Ivo, Bowden Rory, Eriksson Emily M
Аннотация
BACKGROUND: Long COVID is a complex condition where symptoms persist for more than 3 months after SARS-CoV-2 infection and affects an estimated 5-30% of individuals. While persistent inflammation has emerged as an important feature of this condition, it is unclear if immune responses from COVID-19 vaccination or SARS-CoV-2 re-infection exacerbate or mirror the initial inflammatory responses.
METHODS: We quantified 182 inflammatory and neurology-related proteins in plasma using multiplexed affinity proteomics. Plasma samples from the COVID PROFILE cohort conducted in Victoria, Australia, were collected 6-9 months after first infection, but before COVID-19 vaccination from individuals who had recovered from COVID-19 (n = 21) or from individuals with long COVID (n = 12). To establish baseline plasma profiles, protein levels were benchmarked against unvaccinated, SARS-CoV-2 naive individuals (n = 24). In addition, we performed longitudinal analysis in a subset of individuals (n = 34), where paired samples collected 2-4 weeks after a third COVID-19 vaccine dose and after SARS-CoV-2 breakthrough infection were available to assess inflammatory and neurology protein plasma levels after antigen exposure in these contexts.
RESULTS: In this cohort Boruta feature selection and lasso regression models identified IL-20, HAGH, NAAA, CLEC10A, LXN, and MCP-1, TRAIL, G-CSF, NBL1, and CCL23 as best discriminating proteins when comparing the long COVID group to groups of either healthy or COVID-19 recovered. Notably, longitudinal analysis indicated differences in the levels of a subset of plasma proteins following primary infection compared to after COVID-19 booster vaccination and breakthrough infection within the groups.
CONCLUSIONS: These findings suggest that there is an altered immune response outcome primarily observed in individuals with long COVID upon re-exposure.
METHODS: We quantified 182 inflammatory and neurology-related proteins in plasma using multiplexed affinity proteomics. Plasma samples from the COVID PROFILE cohort conducted in Victoria, Australia, were collected 6-9 months after first infection, but before COVID-19 vaccination from individuals who had recovered from COVID-19 (n = 21) or from individuals with long COVID (n = 12). To establish baseline plasma profiles, protein levels were benchmarked against unvaccinated, SARS-CoV-2 naive individuals (n = 24). In addition, we performed longitudinal analysis in a subset of individuals (n = 34), where paired samples collected 2-4 weeks after a third COVID-19 vaccine dose and after SARS-CoV-2 breakthrough infection were available to assess inflammatory and neurology protein plasma levels after antigen exposure in these contexts.
RESULTS: In this cohort Boruta feature selection and lasso regression models identified IL-20, HAGH, NAAA, CLEC10A, LXN, and MCP-1, TRAIL, G-CSF, NBL1, and CCL23 as best discriminating proteins when comparing the long COVID group to groups of either healthy or COVID-19 recovered. Notably, longitudinal analysis indicated differences in the levels of a subset of plasma proteins following primary infection compared to after COVID-19 booster vaccination and breakthrough infection within the groups.
CONCLUSIONS: These findings suggest that there is an altered immune response outcome primarily observed in individuals with long COVID upon re-exposure.