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Role of microRNAs in cognitive decline related to COVID‑19 (Review)
Anastasia Bougea1, Vasiliki Epameinondas Georgakopoulou2, Ioannis G Lempesis2
11st Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Abstract:
The likelihood and severity of cognitive decline related to coronavirus disease 2019 (COVID-19) have been shown to be reflected by the severity of the infection and concomitant alterations in specific biomarkers. The present review discusses the role of microRNAs (miRNAs/miRs) as biomarkers in COVID-19 and the potential molecular mechanisms of cognitive dysfunction related to COVID-19. A systematic search of published articles was carried out from January 31, 2000 to December 31, 2022 using the PubMed, ProQuest, Science Direct and Google Scholar databases, combining the following terms: 'COVID-19' OR 'SARS-CoV-2' OR 'post-COVID-19 effects' OR 'cognitive decline' OR 'neurodegeneration' OR 'microRNAs'. The quality of the evidence was evaluated as high, moderate, low, or very low based on the GRADE rating. A total of 36 studies were identified which demonstrated reduced blood levels of miR-146a, miR-155, Let-7b, miR 31 and miR-21 in patients with COVID-19 in comparison with a healthy group. The overexpression of the Let-7b may result in the downregulation of BCL-2 during COVID-9 by adjusting the immune responses between chronic inflammatory disease, type 2 diabetes, COVID-19 and cognitive impairment. The reduced expression of miR-31 is associated with cognitive dysfunction and increased microcoagulability in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). miR-155 mediates synaptic dysfunction and the dysregulation of neurotransmitters due to acute inflammation, leading to brain atrophy and a subcortical cognitive profile. The downregulation of miR-21 in patients with COVID-19 aggravates systemic inflammation, mediating an uncontrollable immune response and the failure of T-cell function, provoking cognitive impairment in patients with SARS-CoV-2. On the whole, the present review indicates that dysregulated levels of miR-146a, miR-155, Let-7b, miR-31, and miR-21 in the blood of individuals with COVID-19 are associated with cognitive decline, the chronic activation of immune mechanisms, the cytokine storm, and the vicious cycle of damage and systemic inflammation.
Insights
Specific microRNAs (miRNAs) in COVID-19 patients show altered blood levels, impacting cognitive function. Dysregulated miRNAs like miR-146a, miR-155, Let-7b, miR-31, and miR-21 are linked to cognitive decline and inflammation post-COVID-19.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Cognitive decline is a recognized post-COVID-19 effect, with severity linked to infection intensity and specific biomarkers.
- MicroRNAs (miRNAs) are emerging as crucial regulators in various biological processes and disease states.
Purpose of the Study:
- To review the role of miRNAs as biomarkers in COVID-19.
- To explore the molecular mechanisms linking COVID-19 to cognitive dysfunction via miRNAs.
Main Methods:
- A systematic literature search was conducted across major databases (PubMed, ProQuest, Science Direct, Google Scholar) from 2000 to 2022.
- Keywords included COVID-19, SARS-CoV-2, post-COVID-19 effects, cognitive decline, neurodegeneration, and microRNAs.
- Evidence quality was assessed using the GRADE rating system.
Main Results:
- Thirty-six studies revealed reduced blood levels of miR-146a, miR-155, Let-7b, miR-31, and miR-21 in COVID-19 patients compared to healthy individuals.
- Specific miRNAs were associated with distinct mechanisms: miR-31 with cognitive dysfunction and microcoagulability, miR-155 with synaptic dysfunction and brain atrophy, and miR-21 with aggravated inflammation and T-cell dysfunction.
- Let-7b overexpression may influence immune responses and BCL-2 levels, linking chronic inflammation, diabetes, COVID-19, and cognitive impairment.
Conclusions:
- Dysregulated levels of specific miRNAs (miR-146a, miR-155, Let-7b, miR-31, miR-21) in COVID-19 patients are associated with cognitive decline.
- These miRNA alterations are linked to chronic immune activation, cytokine storms, and systemic inflammation, creating a detrimental cycle.
- miRNAs represent potential biomarkers for understanding and potentially treating COVID-19-related cognitive impairment.
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