ArticleEBioMedicine2021
Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis.EBioMedicine · 2023Pooled it
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- Temporal transcriptomics identifies early-response and infection-condition-specific modules guiding host-directed anti-EBOV therapeutics.Microbiology spectrum · 2026Article
- Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection.Nature communications · 2025Article
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- Bioinformatics and molecular biology tools for diagnosis, prevention, treatment and prognosis of COVID-19.Heliyon · 2024Review
- Review
- Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19.The Journal of clinical investigation · 2023Article
- Article
- Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19.Scientific reports · 2023Article
- STAGEs: A web-based tool that integrates data visualization and pathway enrichment analysis for gene expression studies.Scientific reports · 2023Article
- Hyperactive immature state and differential CXCR2 expression of neutrophils in severe COVID-19.Life science alliance · 2023Article
- Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine.NPJ vaccines · 2022Article
- Immune-Related Protein Interaction Network in Severe COVID-19 Patients toward the Identification of Key Proteins and Drug Repurposing.Biomolecules · 2022Article
- Network pharmacology and molecular docking-based investigations of Kochiae Fructus's active phytomolecules, molecular targets, and pathways in treating COVID-19.Frontiers in microbiology · 2022Article
- Review
- Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe coronavirus disease-19 (COVID-19) pandemic has cost lives and economic hardships globally. Various studies have found a number of different factors, such as hyperinflammation and exhausted/suppressed T cell responses to the etiological SARS coronavirus-2 (SARS-CoV-2), being associated with severe COVID-19. However, sieving the causative from associative factors of respiratory dysfunction has remained rudimentary.
methodsWe postulated that the host responses causative of respiratory dysfunction would track most closely with disease progression and resolution and thus be differentiated from other factors that are statistically associated with but not causative of severe COVID-19. To track the temporal dynamics of the host responses involved, we examined the changes in gene expression in whole blood of 6 severe and 4 non-severe COVID-19 patients across 15 different timepoints spanning the nadir of respiratory function.
findingsWe found that neutrophil activation but not type I interferon signaling transcripts tracked most closely with disease progression and resolution. Moreover, transcripts encoding for protein phosphorylation, particularly the serine-threonine kinases, many of which have known T cell proliferation and activation functions, were increased after and may thus contribute to the upswing of respiratory function. Notably, these associative genes were targeted by dexamethasone, but not methylprednisolone, which is consistent with efficacy outcomes in clinical trials.
interpretationOur findings suggest neutrophil activation as a critical factor of respiratory dysfunction in COVID-19. Drugs that target this pathway could be potentially repurposed for the treatment of severe COVID-19.
fundingThis study was sponsored in part by a generous gift from The Hour Glass. EEO and JGL are funded by the National Medical Research Council of Singapore, through the Clinician Scientist Awards awarded by the National Research Foundation of Singapore.
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