Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

Woodruff, Matthew C.; Bonham, Kevin S.; Anam, Fabliha A.; Walker, Tiffany A.; Faliti, Caterina E.; Ishii, Yusho; Kaminski, Candice Y.; Ruunstrom, Martin C.; Cooper, Kelly Rose; Truong, Alexander D.; Dixit, Adviteeya N.; Han, Jenny E.; Ramonell, Richard P.; Haddad, Natalie S.; Rudolph, Mark E.; Yalavarthi, Srilakshmi; Betin, Viktoria; Natoli, Ted; Navaz, Sherwin; Jenks, Scott A.; Zuo, Yu; Knight, Jason S.; Khosroshahi, Arezou; Lee, F. Eun-Hyung; Sanz, Ignacio

doi:10.1038/s41467-023-40012-7

Cited by 56 publications

(48 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also informative were decreasing neutrophil degranulation and fibrosis signatures (Fig. 6b); both phenomena have been associated with long COVID [115, 116].…”

Section: Resultsmentioning

confidence: 99%

“…UV-inactivated virus was used as a control to exclude responses to viral inoculation and restrict the analyses to effects arising from replicating virus. Features often associated with post-acute or long-COVID were not identified, for instance, there were no indications of prolonged infection [127], persistent inflammation [128], impaired lung regeneration [129], fibrosis [116], prolonged T cell activation [130], Th17 bias [131], chronic neutrophil activation [115] or clotting abnormalities [7].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

Carolin,

Yan,

Bishop

et al. 2024

Preprint

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease often characterised by a 'cytokine storm' and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, but where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2 - 66 dpi included biomarkers of severe disease and were associated with 'cytokine storm' pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed.

show abstract

“…Also informative were decreasing neutrophil degranulation and fibrosis signatures (Fig. 6b); both phenomena have been associated with long COVID [115, 116].…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

Carolin,

Yan,

Bishop

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Various groups have observed changes in the inflammatory and coagulation pathways in the plasma proteome of long COVID patients (86)(87)(88). To our knowledge, our study is the first to investigate changes to plasma proteomics following exercise intervention in PCC patients.…”

Section: Exercise Associated Molecular Changes In Pcc Patientsmentioning

confidence: 85%

Impact of a tailored exercise regimen on physical capacity, systemic oxidative stress and plasma proteomic profile in patients affected by post-COVID-19 Condition (PCC)

Chowdhury,

Fontaine,

Lord

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Individuals affected by the post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicates the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases. Methods: Twenty-five women and men with PCC were assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated. Results: Bicep Curl (p=0.040) and STS-30 (p=0.043) improved to a greater extent in the exercise group than in the non-exercise group. An interaction effect was also observed for the level of physical activity (p=0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. After exercise, glutathione levels in PBMCs increased in women but remained unchanged in men. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response (SA100A8) decreasing in the exercise group. Conclusions: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.

show abstract

“…1) was designed to weight the importances from each trained forest, and all “importance” values reported refer to the average fitness-weighted importance across all models. The objective was to give more weight to those with higher benchmarks on the validation sets (or higher generalizability) while penalizing information from highly overfit models, drawing inspiration from the approach used on another work using repeated CV on RFs with high-dimensional, low–sample size datasets ( 76 ). The resulting fitness-weighted importances were used to generate the values in Figs.…”

Section: Methodsmentioning

confidence: 99%

Gut-resident microorganisms and their genes are associated with cognition and neuroanatomy in children

Bonham,

Fahur Bottino,

McCann

et al. 2023

Sci. Adv.

Self Cite

View full text Add to dashboard Cite

Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We investigated the relationship between the microbiome and neuroanatomy and cognition of 381 healthy children, demonstrating that differences in microbial taxa and genes are associated with overall cognitive function and the size of brain regions. Using a combination of statistical and machine learning models, we showed that species including Alistipes obesi , Blautia wexlerae , and Ruminococcus gnavus were enriched or depleted in children with higher cognitive function scores. Microbial metabolism of short-chain fatty acids was also associated with cognitive function. In addition, machine models were able to predict the volume of brain regions from microbial profiles, and taxa that were important in predicting cognitive function were also important for predicting individual brain regions and specific subscales of cognitive function. These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention.

show abstract

Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

Cited by 56 publications

References 38 publications

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

Impact of a tailored exercise regimen on physical capacity, systemic oxidative stress and plasma proteomic profile in patients affected by post-COVID-19 Condition (PCC)

Gut-resident microorganisms and their genes are associated with cognition and neuroanatomy in children

Contact Info

Product

Resources

About