Karina Avendaño-Ortiz

Background: The long-haul symptoms of COVID-19 have not been properly attended, especially those of the central nervous system. Attention, memory and executive functioning are the three main cognitive symptoms reported for long COVID patients. To this day, neurorehabilitation therapy to alleviate these symptoms has not been proposed. Objectives: The current study aims to evaluate the effect of a neurorehabilitation intervention on the three most prevalent symptoms reported for long COVID in Mexican patients: memory, attention and executive functioning. Methods: Subjects were recruited at Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra and underwent a novel neurorehabilitation intervention for 6 months. Baseline measurements were taken using validated instruments (Neuropsi, BANFE and CCQ) before the intervention and after it. Results: A significant decrease in the normalized score of the Memory component of the Neuropsi Atención y Memoria III test was found after the intervention, along with a decrease in two components of the BANFE-III test. Conclusions: In the current study, a successful neuropsychology intervention for the main cognitive symptoms of long COVID in a Mexican population reduced subjective self-perceived complaints and objectively measured cognitive symptoms.

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.