Long COVID Biomarkers and Immune Profiling

1 Gao et al. 2025 — Soluble Biomarkers for Distinct Long COVID Manifestations

Full Citation:: Gao Y, Cai C, Adamo S, Biteus E, Kamal H, Dager L, et al. Identification of soluble biomarkers that associate with distinct manifestations of long COVID. Nature Immunology. 2025;26:692–705. (Gao et al. 2025) DOI:: 10.1038/s41590-025-02135-5 PMID:: 40307449 Study Design:: Multi-cohort prospective study (Swedish + UK cohorts) Key Findings::

- Long COVID patients showed impaired SARS-CoV-2 neutralising antibody responses vs.\ fully recovered individuals
- CD8^+^ T cells showed persistent exhaustion markers (elevated PD-1 and TIM-3) on SARS-CoV-2-specific cells
- Breathlessness subtype: distinct plasma signature of CCL3, CD40, IKBKG, IL-18, and IRAK1 — pointing to apoptotic-inflammatory and platelet activation pathways
- Multi-cohort validated; confirms immunological heterogeneity of Long COVID manifestations

Relevance:: High-quality multi-cohort evidence that Long COVID (and by extension post-COVID ME/CFS) comprises immunologically distinct endotypes. The IRAK1/IL-18/platelet signature for breathlessness links innate TLR signaling and the NLRP3 inflammasome to organ-specific symptoms. Directly applicable to ME/CFS subtyping strategy. Certainty Assessment::

- *Quality:* High (Nature Immunology, multi-cohort validated)
- *Replication:* Multi-cohort validation included in study design
- *Certainty:* 0.80

References

Gao, Yu, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L. Miners, et al. 2025. “Identification of Soluble Biomarkers That Associate with Distinct Manifestations of Long COVID.” Nature Immunology 26: 692–705. https://doi.org/10.1038/s41590-025-02135-5.