Resumen
Introducción: el síndrome post-COVID-19 ocurre 3 meses después de la infección por COVID-19 y tiene una duración mínima de 2 meses. Hay poca información sobre los genes que se encuentran asociados a la desregulación del sistema inmune.
Objetivo: evaluar la expresión génica y su relación con el síndrome post-COVID-19. Materiales y métodos: estudio transversal, retrolectivo y analítico que incluyó 56 pacientes con síndrome post-COVID-19. Se registraron las características clínicas y se analizaron los genes serotonina IL-4, IL-1β, SOCS3, ILF13, e IFNL4 con técnicas de TRIzol® Reagent y técnica PCR-RT.
Resultados: la prevalencia de síndrome post-COVID19 fue 82.1%, sin diferencias en relación con la severidad de los síntomas o comorbilidades. Las características clínicas relacionadas con la presencia del síndrome fueron: sexo mujer, con una razón de momios (RM) de 4.25 (intervalo de confianza [IC 95%] 1.02-17.69) y el consumo de fármacos con RM 8.25 (IC 95% 0.97-70.50). Los factores protectores para fatiga fueron la expresión de serotonina, con una RM 0.238 (0.060-0.949); para problemas en la concentración, la SOCS3 con una RM de 0.188 (0.037-0.946), y para alteraciones en la memoria, el IFNL4 con una RM de 0.094 (0.015-0.586).
Conclusiones: los factores asociados a síndrome post-COVID-19 fueron sexo femenino, consumo de fármacos y desregulación génica de serotonina, IFNL4 y SOCS3.
Abstract
Background: Post-COVID-19 syndrome occurs 3 months after COVID-19 infection and lasts at least 2 months. There is insufficient information on the genes associated with immune system dysregulation.
Objective: To evaluate gene expression and its relationship with post-COVID-19 syndrome.
Materials and methods: Cross-sectional, retrolective and analytical study which included 56 patients with post-COVID-19 syndrome. Clinical characteristics were recorded and serotonin IL-4, IL-1β, SOCS3, ILF13, and IFNL4 genes were analyzed with TRIzol® Reagent and PCR-RT techniques.
Results: the prevalence of post-COVID-19 syndrome was 82.1%, with no differences in relation to the severity of symptoms or comorbidities. The clinical characteristics related to the presence of the syndrome were female sex with an odds ratio (OR) of 4.25 (95% confidence interval [95% CI] 1.02-17.69), and drug consumption with an OR of 8.25 (95% CI 0.97-70.50). Protective factors for fatigue were serotonin expression with an OR of 0.238 (95% CI 0.060-0.949); for concentration problems, SOCS3 with an OR of 0.188 (95% CI 0.037-0.946), and for memory impairment IFNL4 OR 0.094 (95% CI 0.015-0.586).
Conclusions: the associated factors with post-COVID-19 syndrome were female sex, drug use, and gene dysregulation of serotonin, INFL4 and SOCS3.
World Health Organization. WHO COVID-19 Dashboard. Geneva, Switzerland: WHO; 2024. Disponible en: https://data.who.int/dashboards/covid19/deaths?n=
World Health Organization. Post-COVID-19 Conditions Geneva, Switzerland: WHO; 2024. Disponible en: https://www.who.int/teams/health-care-readiness/post-covid-19-condition#:~:text=Common%20symptoms%20include%20fatigue%2C%20shortness,persist%20from%20the%20initial%20illness
Najafi MB, Javanmard SH. Post-COVID-19 Syndrome Mechanisms, Prevention and Management. Int J Prev Med. 2023 May 24;14:59. doi: 10.4103/ijpvm.ijpvm_508_21
Office for National Statistics. Prevalence of long COVID symptoms and COVID-19 complications. UK Office for National Statistics; 16 December 2020. Disponible en: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthandlifeexpectancies/datasets/prevalenceoflongCOVIDsymptomsandCOVID19complications
Nalbandian A, Desai AD, Wan EY. Post-COVID-19 Condition. Annu Rev Med. 2023;74:55-64. doi: 10.1146/annurev-med-043021-030635.
Cellai M, O'Keefe JB. Characterization of Prolonged COVID-19 Symptoms in an Outpatient Telemedicine Clinic. Open Forum Infect Dis. 2020;7(10):ofaa420. doi: 10.1093/ofid/ofaa420
Aiyegbusi OL, Hughes SE, Turner G, et al. Symptoms, complications and management of long COVID: A review. J R Soc Med. 2021;114:428-42.
Schultheiß C, Willscher E, Paschold L, et al. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Rep Med. 2022;3(6):100663. doi: 10.1016/j.xcrm.2022.100663
Croker BA, Kiu H, Nicholson SE. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol. 2008 Aug;19(4):414-22. doi: 10.1016/j.semcdb.2008.07.010
Jafarzadeh A, Nemati M, Jafarzadeh S. Contribution of STAT3 to the pathogenesis of COVID-19. Microb Pathog. 2021;154:104836. doi: 10.1016/j.micpath.2021.104836
Sposito B, Broggi A, Pandolfi L, et al. Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients. bioRxiv [preprint]. 2021 Mar 30:2021.03.30.437173. doi: 10.1101/2021.03.30.437173. Update in: Cell. 2021 Sep 16;184(19):4953-4968.e16
Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021;27(2):258-263. doi: 10.1016/j.cmi.2020.09.052
Wong MC, Huang J, Wong YY, et al. Epidemiology, Symptomatology, and Risk Factors for Long COVID Symptoms: Population-Based, Multicenter Study. JMIR Public Health Surveill. 2023;9:e42315. doi: 10.2196/42315
Müller SA, Isaaka L, Mumm R, et al. Prevalence and risk factors for long COVID and post-COVID-19 condition in Africa: a systematic review. Lancet Glob Health. 2023;11(11):e1713-24. doi: 10.1016/S2214-109X(23)00384-4
Coste J, Tebeka S, Decio V, et al. Prevalence of post-COVID-19 condition in the French general population after the first epidemic waves. Infect Dis Now. 2023;53(1):104631. doi: 10.1016/j.idnow.2022.10.003
Carfi A, Bernabei R, Landi F, et al. COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. J Am Med Assoc.2020;324:603-5.
González-Hermosillo JA, Martínez-López JP, Carrillo-Lampón SA, et al. Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort. Brain Sci. 2021;11(6):760. doi: 10.3390/brainsci11060760
Abdelhafiz AS, Ali A, Maaly AM, et al. Predictors of post-COVID symptoms in Egyptian patients: Drugs used in COVID-19 treatment are incriminated. PLoS One. 2022;17(3):e0266175. doi: 10.1371/journal.pone.0266175
Chen C, Haupert SR, Zimmermann L, et al. Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022;226(9):1593-607. doi: 10.1093/infdis/jiac13635
Davis HE, Assaf GS, McCorkell L, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021;38:101019. doi: 10.1016/j.eclinm.2021.101019
Wong AC, Devason AS, Umana IC, et al. Serotonin reduction in post-acute sequelae of viral infection. Cell. 2023;186(22):4851-67.e20. doi: 10.1016/j.cell.2023.09.013
Farahani RH, Ajam A, Naeini AR. Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial. BMC Infect Dis. 2023;23(1):197. doi: 10.1186/s12879-023-08172-5
Vaz de Paula CB, de Azevedo MLV, Nagashima S, et al. IL-4/IL-13 remodeling pathway of COVID-19 lung injury. Sci Rep. 2020;10(1):18689. doi: 10.1038/s41598-020-75659-5
Modher Nabat Al-Ajrash A, Mohammed Ali SH, Al-Bayaa YJ, et al. Assessment of Interleukin-13(rs20541) Genomic Polymorphism in Patients with Acute Respiratory Distress Syndrome in Relation to COVID19 Infection. Arch Razi Inst. 2022 Dec 31;77(6):2291-2298. doi: 10.22092/ARI.2022.358616.2266
Donlan AN, Sutherland TE, Marie C, et al. IL-13 is a driver of COVID-19 severity. medRxiv [preprint]. 2021:2020.06.18.20134353. doi: 10.1101/2020.06.18.20134353
Yoshida M, Worlock KB, Huang N, et al. Local and systemic responses to SARS-CoV-2 infection in children and adults. Nature. 2022;602(7896):321-7. doi: 10.1038/s41586-021-04345-x
Lin X, Rajagopalan D, Gamage AM, et al. Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity. Nat Commun. 2024;15(1):567. doi:10.1038/s41467-023-44524-0
Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet. 2021;397:220-32.
Liu X, Han J, Cui R, et al. The Promotion of Humoral Immune Responses in Humans via SOCS1-Mediated Th2-Bias Following SARS-CoV-2 Vaccination. Vaccines (Basel). 2023;11(11):1730. doi: 10.3390/vaccines11111730