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SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a “lipid storm”, influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Introdução: O schwanoma ou neurilemoma é um tumor benigno dos nervos periféricos e apresenta-se habitualmente como uma lesão única de crescimento indolente, com origem na proliferação das células de Schwann. Representa uma pequena percentagem dos tumores benignos do membro superior, contudo é o mais frequente de origem neural. Apresentamos um estudo retrospectivo de schwanomas do membro superior para estabelecer a abordagem pré-operatória adequada, avaliar a eficácia do tratamento e observar a evolução pós-operatória. Material e Métodos: Revisão de 17 doentes tratados desde 2007 a 2014 com schwanoma do membro superior e caracterização quanto à idade, sexo, localização no membro superior, sinais e sintomas, exames pré-operatórios, diagnóstico histológico e vigilância pós-operatória. Resultados: Observou-se que em quatro dos doentes, o schwanoma se localizava no braço, três no antebraço, quatro no punho e seis na mão ou dedos. Procedeu-se a excisão com ampliação óptica para optimização do resultado funcional final. A enucleação foi realizada sem lesão fascicular em 12 doentes. Por sua vez, em cinco doentes efectuou-se a excisão dos fascículos envolvidos pela massa. No pós-operatório imediato as parestesias surgiram em nove doentes, regredindo em cinco daqueles no período pósoperatório de 12 meses. Um doente evidenciou défice motor do nervo radial, com recuperação parcial aos 12 meses. Discussão: Os schwanomas são tumores raros, de morfologia bem delimitada, que atingem esporadicamente o membro superior. O diagnóstico pré operatório é pouco frequente, pelo que normalmente apenas se estabelece o diagnóstico após a excisão e o estudo histopatológico. Conclusão: Os schwanomas deverão ser equacionados nas hipóteses de diagnóstico dos nódulos subcutâneos associados a sintomas neurológicos. Assim, é importante investigar a presença de parestesias e o sinal de Tinel, característicos desta lesão. A imagiologia tem um contributo fruste no diagnóstico. Para melhorar o resultado final, o estudo pré-operatório deverá ser criterioso, sendo aconselhável ponderar o benefício da cirurgia face à potencial lesão iatrogénica do nervo.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects ( n = 55), COVID-19 patients ( n = 204), and convalescent individuals ( n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.