340 – Monocyte Dysregulation in PASC With Ongoing Pulmonary Symptoms, 2025, Awamura et al

340 – Monocyte Dysregulation in PASC With Ongoing Pulmonary Symptoms

Thomas K. Awamura, Stefanos Giannakopoulos, Dominic C. Chow, Cecilia M. Shikuma, Gehan Devendra, Vedbar Khadka, Juwon Park

Background
As the number of COVID-19 survivors amongst the global population continues to rise, the rates of chronic sequelae after recovery known as post-acute sequalae of COVID19 (PASC), have increased, emerging as a significant public health concern. Studies have shown that excessive monocyte activation is involved in the development of a cytokine storm and subsequent acute lung injury induced by acute SARS-CoV-2 infection. However, long-term consequence of COVID-19 on monocyte dysregulation and its contribution to PASC development has not been fully understood. We characterized transcriptomic changes in circulating monocytes associated with PASC with persistent pulmonary symptoms (PPASC) and how it affects inflammation and persistence of pulmonary symptoms.

Methods
A total of 31 monocyte RNA samples were collected from blood of the study participants enrolled in three groups: individuals with PASC with pulmonary symptoms (PPASC, n=14), individuals who recovered from COVID-19 infection but no residual symptoms (Recovered, n=8), and healthy individuals with no COVID-19 infection confirmed by antibody test (Healthy, n=9). Transcriptomic profiling of monocytes was performed by bulk RNA sequencing to determine the relationship between monocytes states among the groups. Ingenuity pathway analysis (IPA) was used to identify relevant dysregulated cellular pathways and associated disease pathways.

Results
In comparison to Recovered and Healthy, PPASC had an enrichment of immune activation signatures, such as neutrophil degranulation, production of nitric oxide and reactive oxygen species in macrophages, and IL-8 and IL-6 signaling, while IL-10 pathway was down-regulated (Figure 1). Monocytes from PPASC displayed up-regulation of pathways associated with immune responses of macrophages and chronic inflammation. Disease pathway analysis showed genes associated with inflammation and pulmonary diseases, such as chronic inflammatory disorder, vasculitis, and interstitial pneumonia, were activated in PPASC compared to Recovered.

Conclusions
Transcriptomic analysis revealed that monocytes from PPASC individuals were continuously dysregulated with up regulation of pathways associated with immune activation, inflammation, and fibrosis. However, the gene signatures of monocytes from Recovered were comparatively similar to those of Healthy. Our data demonstrates that monocyte dysregulation persists after viral resolution, impacting the pulmonary sequelae in PASC individuals.

Link (Conference on Retroviruses and Opportunistic Infections) [Abstract Only]