tetano
Editor, Senior Moderator
Front Immunol
. 2026 Aug 27:17:1913045.
doi: 10.3389/fimmu.2026.1913045. eCollection 2026.
Yang Wu # 1 , Yu Kit Chan # 2 3 , Denise Goh # 1 , Belinda Lee # 4 , Felicia Wee 1 , Mai Chan Lau 5 , Paul Chui 4 , Thuan Tong Tan 6 , Jabed Iqbal 7 , Akhila Balachander 8 , Craig Ryan Joseph 9 , Lisa F P Ng 10 , Yee Sin Leo 2 3 11 12 , Joe Yeong 13 14 15 16 17 18 19
Affiliations Expand
Persistent inflammation and tissue injury may contribute to post-acute COVID-19 syndrome (PACS). However, direct tissue evidence from mildly-infected individuals sampled long after recovery remains exceptionally limited. Here, we performed post-mortem bulk RNA-seq and GeoMx digital spatial profiling of lung, heart, and brain tissues from four individuals who recovered from mild COVID-19 more than 250 days before death from unrelated causes. Samples were collected during the early phase of the national vaccination program, before widespread vaccine uptake and recurrent infection, providing a rare reference cohort for defining tissue responses to SARS-CoV-2 in the absence of major confounding from vaccination and/or reinfection; such a cohort can no longer be prospectively assembled. We observed residual SARS-CoV-2 nucleocapsid antigen within tissues and revealed organ-specific immune alterations. Lung and heart tissues exhibited a coordinated, self-sustaining inflammatory response, whereas brain tissue showed vascular dysfunction and altered neuroimmune homeostasis. These findings showcase the distinct tissue responses following mild infection and provide a spatially resolved view of sub-clinical long-term tissue sequelae. Collectively, our data establish a unique baseline for persistent viral antigen and tissue-specific immune dysregulation underlying PACS.
Keywords: SARS-CoV-2; immune dysregulation; macrophage; post-acute COVID-19 syndrome (PACS); post-mortem cohort; spatial transcriptomics; tissue inflammation; viral persistence.
. 2026 Aug 27:17:1913045.
doi: 10.3389/fimmu.2026.1913045. eCollection 2026.
Case Report: Post-mortem analysis of long-term inflammation after mild COVID-19
Yang Wu # 1 , Yu Kit Chan # 2 3 , Denise Goh # 1 , Belinda Lee # 4 , Felicia Wee 1 , Mai Chan Lau 5 , Paul Chui 4 , Thuan Tong Tan 6 , Jabed Iqbal 7 , Akhila Balachander 8 , Craig Ryan Joseph 9 , Lisa F P Ng 10 , Yee Sin Leo 2 3 11 12 , Joe Yeong 13 14 15 16 17 18 19
Affiliations Expand
- PMID: 42725054
- PMCID: PMC13559925
- DOI: 10.3389/fimmu.2026.1913045
Abstract
Persistent inflammation and tissue injury may contribute to post-acute COVID-19 syndrome (PACS). However, direct tissue evidence from mildly-infected individuals sampled long after recovery remains exceptionally limited. Here, we performed post-mortem bulk RNA-seq and GeoMx digital spatial profiling of lung, heart, and brain tissues from four individuals who recovered from mild COVID-19 more than 250 days before death from unrelated causes. Samples were collected during the early phase of the national vaccination program, before widespread vaccine uptake and recurrent infection, providing a rare reference cohort for defining tissue responses to SARS-CoV-2 in the absence of major confounding from vaccination and/or reinfection; such a cohort can no longer be prospectively assembled. We observed residual SARS-CoV-2 nucleocapsid antigen within tissues and revealed organ-specific immune alterations. Lung and heart tissues exhibited a coordinated, self-sustaining inflammatory response, whereas brain tissue showed vascular dysfunction and altered neuroimmune homeostasis. These findings showcase the distinct tissue responses following mild infection and provide a spatially resolved view of sub-clinical long-term tissue sequelae. Collectively, our data establish a unique baseline for persistent viral antigen and tissue-specific immune dysregulation underlying PACS.
Keywords: SARS-CoV-2; immune dysregulation; macrophage; post-acute COVID-19 syndrome (PACS); post-mortem cohort; spatial transcriptomics; tissue inflammation; viral persistence.