Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review

Abstract

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood–nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.

Differentially‐regulated miRNAs in COVID‐19: A systematic review

“…Interestingly, from this list miR‐15a‐5p and miR‐31‐5p appeared in two or more studies 56,57,73,78,82,84,86 and could potentially serve as biomarkers for disease severity. Table 3 summarises the targets and principle cellular pathways associated with miRNAs regulated during Inf vs C and S vs C stages and cited previously 46,56,73,88–120 . Most of the miRNAs were involved in targeting virus‐host interactions, viral replication, and host‐immune responses.…”

The impact of COVID-19 on microRNA and CD marker expression in AML patients

“…In a systematic review by Reyes-Long et al (2023), they have demonstrated that microRNA expression levels differ between COVID-19 positive and negative patients, and these differences may be associated with the upregulation or downregulation of specific microRNAs 55 . Additionally, in the study by Shi et al (2022), differences in microRNA expression among patients are observed 56 .…”

Bioinformatics analysis and initial validation of potential therapeutic targets for COVID-19 infection in osteoarthritis patients

“…Of all miRNAs, hsa-miR-29b-3p appears to wield a potent regulatory in uence on the advancement of OA 39 . The miRNAs hsa-miR-29a,b,c-3p might be intricately linked to the pathogenic process of SARS-CoV-2 infection via engagement with the IL-6/STAT3 pathway 40 . Research has demonstrated a potential close correlation between hsa-miR-145-5p and the growth of airway smooth muscle cells, which could potentially in uence the prognosis of patients with COVID-19 41 .…”