tetano
Editor, Senior Moderator
Front Immunol
. 2024 Dec 3:15:1450853.
doi: 10.3389/fimmu.2024.1450853. eCollection 2024. A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals
Daniel Missailidis[SUP] #[/SUP][SUP] 1 [/SUP], Esmaeil Ebrahimie[SUP] #[/SUP][SUP] 2 3 [/SUP], Manijeh Mohammadi Dehcheshmeh[SUP] 2 [/SUP], Claire Allan[SUP] 1 [/SUP], Oana Sanislav[SUP] 1 [/SUP], Paul Fisher[SUP] 1 [/SUP], Stephanie Gras[SUP] 4 5 6 [/SUP], Sarah J Annesley[SUP] 1 [/SUP]
Affiliations
Introduction: Long COVID is a debilitating condition that lasts for more than three months post-infection by SARS-CoV-2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.
Methods: In this pilot study we used RNA-Seq to quantify the transcriptomes of peripheral blood mononuclear cells isolated from COVID-recovered individuals, seven with and seven without Long COVID symptoms (age- and sex-matched individuals), on average 6 months after infection.
Results: Seventy genes were identified as significantly up- or down-regulated in Long COVID samples, and the vast majority were downregulated. The most significantly up- or downregulated genes fell into two main categories, either associated with cell survival or with inflammation. This included genes such as ICOS (FDR p = 0.024) and S1PR1 (FDR p = 0.019) that were both up-regulated, indicating that a pro-inflammatory state is sustained in Long COVID PBMCs compared with COVID recovered PBMCs. Functional enrichment analysis identified that immune-related functions were expectedly predominant among the up- or down-regulated genes. The most frequently downregulated genes in significantly altered functional categories were two leukocyte immunoglobulin like receptors LILRB1 (FDR p = 0.005) and LILRB2 (FDR p = 0.027). PCA analysis demonstrated that LILRB1 and LILRB2 expression discriminated all of the Long COVID samples from COVID recovered samples.
Discussion: Downregulation of these inhibitory receptors similarly indicates a sustained pro-inflammatory state in Long COVID PBMCs. LILRB1 and LILRB2 should be validated as prospective biomarkers of Long COVID in larger cohorts, over time and against clinically overlapping conditions.
Keywords: COVID-19; LILRB1; LILRB2; Long COVID; biomarker; inflammation; transcriptomics.
. 2024 Dec 3:15:1450853.
doi: 10.3389/fimmu.2024.1450853. eCollection 2024. A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals
Daniel Missailidis[SUP] #[/SUP][SUP] 1 [/SUP], Esmaeil Ebrahimie[SUP] #[/SUP][SUP] 2 3 [/SUP], Manijeh Mohammadi Dehcheshmeh[SUP] 2 [/SUP], Claire Allan[SUP] 1 [/SUP], Oana Sanislav[SUP] 1 [/SUP], Paul Fisher[SUP] 1 [/SUP], Stephanie Gras[SUP] 4 5 6 [/SUP], Sarah J Annesley[SUP] 1 [/SUP]
Affiliations
- PMID: 39691709
- PMCID: PMC11649547
- DOI: 10.3389/fimmu.2024.1450853
Introduction: Long COVID is a debilitating condition that lasts for more than three months post-infection by SARS-CoV-2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.
Methods: In this pilot study we used RNA-Seq to quantify the transcriptomes of peripheral blood mononuclear cells isolated from COVID-recovered individuals, seven with and seven without Long COVID symptoms (age- and sex-matched individuals), on average 6 months after infection.
Results: Seventy genes were identified as significantly up- or down-regulated in Long COVID samples, and the vast majority were downregulated. The most significantly up- or downregulated genes fell into two main categories, either associated with cell survival or with inflammation. This included genes such as ICOS (FDR p = 0.024) and S1PR1 (FDR p = 0.019) that were both up-regulated, indicating that a pro-inflammatory state is sustained in Long COVID PBMCs compared with COVID recovered PBMCs. Functional enrichment analysis identified that immune-related functions were expectedly predominant among the up- or down-regulated genes. The most frequently downregulated genes in significantly altered functional categories were two leukocyte immunoglobulin like receptors LILRB1 (FDR p = 0.005) and LILRB2 (FDR p = 0.027). PCA analysis demonstrated that LILRB1 and LILRB2 expression discriminated all of the Long COVID samples from COVID recovered samples.
Discussion: Downregulation of these inhibitory receptors similarly indicates a sustained pro-inflammatory state in Long COVID PBMCs. LILRB1 and LILRB2 should be validated as prospective biomarkers of Long COVID in larger cohorts, over time and against clinically overlapping conditions.
Keywords: COVID-19; LILRB1; LILRB2; Long COVID; biomarker; inflammation; transcriptomics.