Factores genéticos asociados a long COVID / Genetic factors associated with long COVID

Introducción: La variabilidad de la expresión y la evolución de la COVID no se explican completamente por los factores clínicos, atribuyéndose un importante papel a los genéticos. Además, se ha planteado si los mismos componentes genéticos que participan en la susceptibilidad y gravedad de la infección influyen en su evolución hacia long COVID. Como objetivo nos propusimos revisar la literatura a fin de conocer cuáles son los factores genéticos que intervienen en la génesis de la COVID persistente. Material y métodos: Revisión sistemática en PubMed y repositorios bioRxiv y medRxiv con base en los descriptores y términos Medical Subject Headings (MeSH) relacionados con COVID y factores genéticos. Fueron seleccionados 2.705 artículos. Un primer cribado, realizado de manera independiente por los autores, redujo la lista a 205 y finalmente, tras un análisis más detallado, se eligieron 85 trabajos para su lectura completa y revisión. Resultados: La enzima convertidora de angiotensina 2 (ACE2) y la proteasa transmembrana, serina 6 (TMPSS6) están implicadas en la susceptibilidad, sin embargo, no se ha encontrado su participación en long COVID. Sí se han hallado algunas asociaciones entre genes, que intervienen en la respuesta inflamatoria e inmune, con la gravedad de la enfermedad y el desarrollo de long COVID. La relación más importante se ha observado en el locus FOXP4. Conclusiones: Aunque actualmente la información sobre long COVID es limitada, parece claro que los factores genéticos identificados hasta ahora no justifican la progresión hacia una enfermedad persistente y se debe considerar la participación de otros componentes como la acción poligénica, de genes pleiotrópicos, de la microbiota y de los cambios epigenéticos.(AU)

Introduction: The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID. Material and methods: Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review. Results: Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus. Conclusions: Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.(AU)

[Genetic factors associated with long COVID]. / Factores genéticos asociados a long COVID.

INTRODUCTION: The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID. MATERIAL AND METHODS: Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review. RESULTS: Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus. CONCLUSIONS: Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.

Insights for COVID-19 in 2023 / Perspectivas de COVID-19 para 2023

Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources. (AU)

Las predicciones para un próximo fin de la pandemia de la Organización Mundial de la Salud deben interpretarse con precaución. La evidencia actual indica que la eficacia de una cuarta dosis de las vacunas clásicas ARNm (BNT162b2 o mRNA-1273) es baja y de corta duración para prevenir la infección de SARS-CoV-2 en su variante predominante (Omicron). No obstante, su eficacia es alta frente a la infección sintomática grave, hospitalización y muerte. Las nuevas vacunas que están siendo introducidas son bivalentes y activas frente a las variantes Omicron. Entre las potenciales nuevas vacunas que se introducirán en el próximo año, se encuentra una vacuna basada en una proteína recombinante que emula el dominio de unión al receptor de la proteína Spike en desarrollo por la compañía española Hipra, así como vacunas de administración nasal u oral. La información disponible apunta a que las vacunas frente al COVID-19 podrán administrarse asociadas a la vacunación antigripal sin particulares complicaciones. Se encuentran en investigación nuevos fármacos frente a COVID-19 tanto antivirales como anti-inflamatorios pero no parece ocurrir lo mismo con los anticuerpos monoclonales. La indicación de utilizar mascarillas en algunas circunstancias se mantendrá el próximo año en vista a la acumulación de datos científicos sobre su eficacia. Finalmente, el síndrome del COVID largo o Post-COVID puede que siga afectando a una proporción muy elevada de los pacientes que sufrieron la enfermedad, requiriendo recursos diagnósticos y terapéuticos combinados. (AU)

Mielitis transversa aguda asociada con infección por SARS-CoV-2 / Acute Transverse Myelitis Associated to SARS-CoV-2 Infection

Resumen Además de provocar problemas respiratorios, la infección con el SARS-CoV-2 puede causar un espectro amplio de complicaciones neurológicas como son cefalea, ageusia, anosmia, encefalopatía, enfermedad cerebrovascular, síndrome de Guillain-Barré y otras polineuropatías, meningoencefalitis, encefalopatía hemorrágica necrotizante aguda y síndromes del sistema nervioso central asociados a inflamación. En esta revisión presentamos 39 casos de mielitis transversa aguda (MTA) asociados a infección por el SARS-CoV-2, confirmado por una prueba de reacción en cadena de la polimerasa (PCR) por hisopado nasofaríngeo y/o de antígeno en plasma. Los análisis bioquímicos de los pacientes confirmaron la ausencia de otros patógenos y de autoanticuerpos involucrados en inflamación del sistema nervioso, excepto por 2 casos, uno con autoanticuerpos contra la glicoproteína de la mielina de los oligodendrocitos (anti-MOG IgG) y otro con anti-MOG IgG y antidescarboxilasa del ácido glutámico (anti-GAD65), indicativos de una enfermedad autoinmune del sistema nervioso central. Los estudios de imagenología de resonancia magnética (RMN) confirmaron el diagnóstico de MTA. Aunque no se puede inferir causalidad, es muy probable que los casos aislados de MTA sean consecuencia de un proceso para o postinfeccioso en la COVID-19. La comprensión de los mecanismos que desencadenan estos trastornos neurológicos durante o al final de la infección viral, ayudarán a optimizar las estrategias terapéuticas para el manejo del paciente.

Abstract In addition to causing respiratory problems, SARS-CoV-2 can cause a wide spectrum of neurological complications such as headaches, ageusia, anosmia, encephalopathy, cerebrovascular disease, Guillain-Barré syndrome and other polyneuropathies, meningoencephalitis, acute necrotizing hemorrhagic encephalopathy, and central nervous system syndromes associated with inflammation. In this review we present 39 cases of acute transverse myelitis (ATM) associated to SARS-CoV-2 infection. All cases had a positive polymerase chain reaction (PCR) nasopharyngeal swab and/or antigen test. Biochemical analyses confirmed the absence of other pathogens and autoantibody-mediated neuroinflammatory disease, except for two cases, one with autoantibodies against the oligodendrocyte myelin glycoprotein (anti-MOG IgG) and another with anti-MOG IgG and anti-glutamic acid decarboxylase (anti-GAD65). Magnetic Resonance Imaging (MRI) studies confirmed the diagnosis of ATM. Although causality cannot be inferred, it is likely that isolated cases of ATM are the consequence of a para or post-infectious process in SARS-CoV-2. In this work, the probable causes of ATM associated with SARS-CoV-2 are discussed. The understanding of the mechanisms behind these neurological disorders triggered by a viral infection will help to optimize the therapeutic strategies for patient management.

Prevalence and factors associated with long COVID in adults from Southern Brazil: findings from the PAMPA cohort / Prevalência e fatores associados à COVID longa em adultos do Sul do Brasil: achados da coorte PAMPA / Prevalencia y factores asociados con el COVID largo en adultos del Sur de Brasil: hallazgos de la cohorte PAMPA

Abstract: Most COVID-19 survivors have reported experiencing persistent symptoms after the infection - these types of cases are known as long COVID. Since Brazil was an epicenter of the COVID-19 pandemic, a high burden of long COVID is expected. This study aimed to identify the prevalence and factors associated with long COVID in adults in Southern Brazil, analyzing data from the PAMPA cohort. Participants filled out a self-reported online questionnaire in June 2022. This study only included subjects who tested positive for COVID-19. Long COVID was defined by any symptoms that persisted for at least three months after the SARS-CoV-2 infection. Poisson's regression models with robust variance were used to identify factors associated with long COVID; and results were reported as prevalence ratios (PR) and respective 95% confidence intervals (95%CI). A total of 1,001 participants (77.4% women, mean age [SD] = 38.3 [11.9] years) were analyzed. The prevalence of long COVID among these patients was 77.4% (95%CI: 74.7; 79.9). The likelihood of long COVID was higher in unvaccinated participants (PR = 1.23, 95%CI: 1.06; 1.42), in those with chronic conditions (PR = 1.13, 95%CI: 1.04; 1.24), and in those who were hospitalized due to the COVID-19 infection (PR = 1.24, 95%CI: 1.16; 1.32). This prevalence was also higher in women (PR = 1.21, 95%CI: 1.09; 1.33) than in men. Physical activity was associated with a reduced likelihood of fatigue, neurological complications, coughing, and headaches as persistent symptoms after a COVID-19 infection. It was found that three out of four adults in Southern Brazil experienced long COVID. Public policies aiming to reduce the burden of long COVID must be prioritized, especially in groups that are at higher risk of developing this harmful condition.

Resumo: A maior parte dos sobreviventes da COVID-19 relatou sintomas persistentes após a infecção, também conhecida como COVID longa. O Brasil foi um epicentro da pandemia de COVID-19, logo, espera-se uma alta carga de COVID longa. Este estudo teve como objetivo identificar a prevalência e os fatores associados à COVID longa em adultos no Sul do Brasil. Foram analisados dados da coorte PAMPA. Os participantes preencheram um questionário online autoaplicável em junho de 2022. Foram incluídos apenas os participantes que testaram positivo para COVID-19. A COVID longa foi definida como qualquer sintoma que persistiu por pelo menos três meses após a infecção do SARS-CoV-2. Os modelos de regressão de Poisson com variância robusta foram usados para identificar fatores associados à COVID longa; os resultados foram relatados como razão de prevalência (RP) e seus respectivos intervalos de 95% de confiança (IC95%). Ao todo, 1.001 participantes (77,4% mulheres, idade média [DP] = 38,3 [11,9] anos) foram analisados. A prevalência da COVID longa foi de 77,4% (IC95%: 74,7; 79,9). A probabilidade da COVID longa foi maior em participantes não vacinados (RP = 1,23, IC95%: 1,06; 1,42), pessoas com condições crônicas (RP = 1,13, IC95%: 1,04; 1,24), e pacientes hospitalizados devido à infecção por COVID-19 (RP = 1,24, IC95%: 1,16; 1,32) em comparação com as contrapartes. A prevalência foi maior em mulheres (RP = 1,21, IC95%: 1,09; 1,33) do que em homens. A atividade física foi associada à probabilidade reduzida de fadiga, complicações neurológicas, tosse e dor de cabeça como sintomas persistentes após a infecção por COVID-19. Três em cada quatro adultos no Sul do Brasil tiveram COVID longa. Políticas públicas que visem reduzir a carga da covid longa devem ser priorizadas, especialmente nos grupos de maior risco desta condição.

Resumen: La mayoría de los supervivientes de la COVID-19 relató síntomas persistentes tras la infección, también conocida como COVID largo. Brasil fue un epicentro de la pandemia de COVID-19, así, se espera una alta carga de COVID largo. El objetivo de este estudio fue identificar la prevalencia y los factores asociados con la COVID largo en adultos en el Sur de Brasil. Se analizaron datos de la cohorte PAMPA. Los participantes rellenaron un cuestionario en línea autoadministrado en junio de 2022. Solo se incluyeron los participantes que dieron positivo para COVID-19. La COVID largo fue definida como cualquier síntoma que persistió durante al menos tres meses tras la infección del SARS-CoV-2. Se utilizaron los modelos de regresión de Poisson con varianza robusta para identificar factores asociados con el COVID largo; se relataron los resultados como razón de prevalencia (RP) y sus respectivos intervalos de 95% confianza de 95% (IC95%). En total, se analizaron 1.001 participantes (el 77,4% mujeres, edad media [DP] = 38,3 [11,9] años). La prevalencia del COVID largo fue del 77,4% (IC95%: 74,7; 79,9). La probabilidad del COVID largo fue más alta en participantes no vacunados (RP = 1,23, IC95%: 1,06; 1,42), personas con condiciones crónicas (RP = 1,13, IC95%: 1,04; 1,24) y pacientes hospitalizados debido a la infección por COVID-19 (RP = 1,24, IC95%: 1,16; 1,32) en comparación con sus contrapartes. La prevalencia fue más alta en mujeres (RP = 1,21, IC95%: 1,09; 1,33) que en hombres. La actividad física se asoció con la probabilidad reducida de fatiga, complicaciones neurológicas, tos y dolor de cabeza como síntomas persistentes tras la infección por COVID-19. Tres de cada cuatro adultos en el Sur de Brasil han tenido COVID largo. Se deben priorizar las políticas públicas destinadas a reducir la carga del COVID largo, sobre todo en los grupos de mayor riesgo para esta condición.