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Life Sci Alliance ; 5(4)2022 04.
Article in English | MEDLINE | ID: covidwho-1637974


Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model of SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at predefined time points in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication were limited. Transcriptional signatures of inflammation-associated genes in bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both cohorts. However, age-specific divergence of immune responses emerged during the post-acute phase. Older animals exhibited sustained local inflammatory innate responses, whereas local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, and persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling suggests that age may delay or impair antiviral cellular immune responses and delay efficient return to immune homeostasis.

Aging/immunology , COVID-19/immunology , COVID-19/veterinary , SARS-CoV-2/immunology , Acute Disease , Animals , Antibody Formation/immunology , Bronchoalveolar Lavage Fluid , COVID-19/complications , COVID-19/genetics , Cytokines/blood , Gene Expression Regulation , Gene Regulatory Networks , Genomics , Immunity, Cellular/genetics , Immunomodulation , Inflammation/complications , Inflammation/pathology , Lung/immunology , Lung/pathology , Lung/virology , Lymphoid Tissue/pathology , Macaca mulatta/immunology , Macaca mulatta/virology , Models, Biological , Single-Cell Analysis , T-Lymphocytes/immunology , Transcription, Genetic
Rev Neurol ; 72(11): 397-406, 2021 06 01.
Article in English, Spanish | MEDLINE | ID: covidwho-1248580


INTRODUCTION: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). AIM: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. CONCLUSIONS: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.

TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).Introducción. Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones. Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.

COVID-19/epidemiology , Multiple Sclerosis , Biomarkers , Central Nervous System/diagnostic imaging , Comorbidity , Environmental Exposure , Epigenesis, Genetic , Europe , Gray Matter/pathology , Humans , Life Style , Lymphocyte Subsets/immunology , Lymphoid Tissue/pathology , Meninges/pathology , Microbiota , Multiple Sclerosis/epidemiology , Multiple Sclerosis/genetics , Multiple Sclerosis/microbiology , Multiple Sclerosis/pathology , Neuroglia/pathology , Neurology/trends , Neurons/pathology , Remyelination
J Clin Pathol ; 74(8): 522-527, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-733145


AIMS: The global outbreak of COVID-19 has resulted in an increased mortality. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs is still unclear. In this study, postmortem percutaneous biopsies of multiple organs from deceased patients were performed to understand the histopathological changes caused by COVID-19. METHODS: Biopsy specimens of pulmonary, cardiac, hepatic and lymphoid tissues were obtained from three patients, who died due to COVID-19 pneumonia. H&E stain, Masson trichrome stain, immunohistochemistry stain and in-situ hybridisation were used. RESULTS: Pulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD). In the early phase, the histological findings were mainly those of exudative features of DAD. The later phase was characterised by organisation of DAD combined with bacterial pneumonia. No serious damage was found in the bronchiolar epithelium and submucosal glands. The hepatic tissue revealed features of ischaemic necrosis, but findings suggestive of mild lobular hepatitis were also observed. The lymphoid tissue revealed features of non-specific acute lymphadenitis. The cardiac tissue revealed changes of underlying disease. SARS-CoV-2 RNAs were not detected in hepatocytes, cholangiocytes and lymphocytes of lymph nodes. CONCLUSIONS: COVID-19 predominantly involves the pulmonary tissue, causes DAD and aggravates the cardiovascular disease. However, other extrapulmonary tissues did not reveal any virus-specific findings, but were affected by multiple factors. The findings in this report caution the pathologists that they should not mistakenly attribute all the histological features to CoV infection. Moreover, the clinicians should pay attention to the potentially injurious and correctable causes.

COVID-19/pathology , Liver/pathology , Lung/pathology , Lymphoid Tissue/pathology , Myocardium/pathology , Aged , Aged, 80 and over , Biopsy, Large-Core Needle , COVID-19/immunology , COVID-19/virology , COVID-19 Nucleic Acid Testing , Fatal Outcome , Female , Humans , Immunohistochemistry , In Situ Hybridization , Lung/virology , Lymphoid Tissue/immunology , Male , Myocardium/chemistry , Predictive Value of Tests