ArticleBrain, behavior, and immunity2023
Substance P and Prokineticin-2 are overexpressed in olfactory neurons and play differential roles in persons with persistent post-COVID-19 olfactory dysfunction.
Article in Brain, behavior, and immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.Journal of neurology · 2023Pooled it
- Comparisons between anosmia and ageusia with neurological symptoms and cardiorespiratory fitness among post-COVID-19 individuals: a cross-sectional study.Acta neurologica Belgica · 2026Article
- Article
- Neuropeptide and cytokines expression in long COVID-19 related neuropsychological sequelae: insights into NK1R-mediated neuroinflammation andFrontiers in cellular neuroscience · 2026Article
- Systemic role of orexin A, substance P, bradykinin, and DABK in severe COVID-19 and 2.5-yr follow-ups: an observational study.BJA open · 2025Article
- Post-COVID-19 Hyposmia Does Not Exhibit Main Neurodegeneration Markers in the Olfactory Pathway.Molecular neurobiology · 2024Article
- Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives.Biomolecules · 2024Review
- Mechanisms of COVID-19-associated olfactory dysfunction.Neuropathology and applied neurobiology · 2024Review
- Substance P - a regulatory peptide with defense and repair functions. Results and perspectives for the fight against COVID-19.Frontiers in neurology · 2024Article
- Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.Pharmacological reviews · 2023Review
- Risk factors for post-COVID cognitive dysfunctions: the impact of psychosocial vulnerability.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- The role of Substance P in the defense line of the respiratory tract and neurological manifestations post COVID-19 infection.Frontiers in neurology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent olfactory dysfunction (OD) is one of the most complaining and worrying complications of long COVID-19 because of the potential long-term neurological consequences. While causes of OD in the acute phases of the SARS-CoV-2 infection have been figured out, reasons for persistent OD are still unclear. Here we investigated the activity of two inflammatory pathways tightly linked with olfaction pathophysiology, namely Substance P (SP) and Prokineticin-2 (PK2), directly within the olfactory neurons (ONs) of patients to understand mechanisms of persistent post-COVID-19 OD. ONs were collected by non-invasive brushing from ten patients with persistent post-COVID-19 OD and ten healthy controls. Gene expression levels of SP, Neurokinin receptor 1, Interleukin-1β (IL-1β), PK2, PK2 receptors type 1 and 2, and Prokineticin-2-long peptide were measured in ONs by Real Time-PCR in both the groups, and correlated with residual olfaction. Immunofluorescence staining was also performed to quantify SP and PK2 proteins. OD patients, compared to controls, exhibited increased levels of both SP and PK2 in ONs, the latter proportional to residual olfaction. This work provided unprecedented, preliminary evidence that both SP and PK2 pathways may have a role in persistent post-COVID-19 OD. Namely, if the sustained activation of SP, lasting months after infection's resolution, might foster chronic inflammation and contribute to hyposmia, the PK2 expression could instead support the smell recovery.
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