Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

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.

Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells.

COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV-2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppresses macrophage anti-inflammation and efficient tissue repair programs and provides mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.

sTREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity.

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

Zika Virus Meningoencephalitis in an Immunocompromised Patient.

The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.

Pneumonia comunitária e pneumonia hospitalar em adultos / Community-acquired pneumonia and nosocomial pneumonia in adults

Pneumonia bacteriana comunitária e hospitalar em adultos são problemas de saúde pública crescentes, com inúmeras internações anualmente e causas frequentes de morbimortalidade. A rápida caracterização do quadro clínico deve ser acompanhada de decisão quanto à necessidade de internação do paciente e o tratamento deve ser baseado na gravidade da apresentação e aspectos epidemiológicos. O acompanhamento clínico é imprescindível, tanto ambulatorialmente quanto na internação, atento aos critérios de falha terapêutica e necessidade de revisão da terapêutica inicialmente instituída. Particularmente na pneumonia hospitalar (nosocomial), o diagnóstico é um desafio e a análise do tempo do início do quadro é fundamental para o direcionamento empírico do tratamento. Ênfase na prevenção é uma tentativa de redução na frequência dos casos.

Community and hospital acquired bacterial pneumonia in adults are increasing public health problems, with numerous hospitalizations annually and frequent causes of morbidity and mortality. Rapid characterization of the clinical picture must be accompanied by a decision regarding the need for patient hospitalization and treatment should be based on severity of presentation and epidemiological aspects. The follow up is essential, both outpatient and in hospital, in keeping with the criteria of treatment failure and need for review of initial treatment. Particularly in hospital-acquired pneumonia (nosocomial), the diagnosisis a challenge and analysis of time of onset is crucial for directing empirical treatment. Emphasison prevention is an attempt to reduce the frequency of cases.

Uso racional de antimicrobianos / Rational use of antimicrobials

A administração inadequada de antimicrobianos é capaz de comprometer a resposta clínica do paciente, aumentar custos com internação e contribuir para o surgimento de bactérias multirresistentes. Nesse contexto, o uso racional de antimicrobianos é benéfico para o paciente infectado e também para a instituição de saúde. A indicação desta classe de drogas deve levar em conta o hospedeiro, o agente infeccioso e o antimicrobiano propriamente dito. Assim, sua utilização deve ser baseada no conhecimento dos conceitos de colonização, contaminação e infecção, noções de microbiologia clínica, coleta de culturas, microbiota habitual do corpo humano, e mecanismos, espectro de ação, farmacocinética, farmacodinâmica e efeitos colaterais dos antimicrobianos. A revisão desses tópicos procura fornecer subsídios para escolha do antimicrobiano mais adequado para o tipo de infecção, tempo de tratamento previsto, critérios de falha e resposta clínica à droga prescrita, além de nortear possível troca de terapia ao longo do tratamento.

The inadequate administration of antimicrobials may compromise the clinical response of the patient, increase the costs during hospitalization and contribute to the appearance of multiresistant bacteria. In this context, the use of rational antimicrobials is beneficial to the infected patient and also to the health institution. The prescription of this drug type must take in account the host, the infectious agent and the antimicrobial itself. Thus, its utilization must be based on the knowledge of the concepts of colonization, contamination and infection, notions of clinical microbiology, culture collection, and habitual microbiota of the human body, and mechanisms, action specter, pharmacokinetics, pharmacodynamics and side effects of the antimicrobials. The revision of these topics pursuits to provide subsidies to the choice of the most adequate antimicrobial to the type of infection, foreseen treatment time, failure criteria and clinical answer to the prescribed drug, besides guide possible change of therapy along the treatment.

Infecção do trato urinário / Urinary tract infection

A infecção do trato urinário (ITU) é uma das causas mais comuns de infecção na população geral. É mais prevalente no sexo feminino, mas também acomete pacientes do sexo masculino principalmente quando associada à manipulação do trato urinário e à doença prostática. A ITU pode ser classificada quanto à localização em ITU baixa (cistite) e ITU alta (pielonefrite) e quanto à presença de fatores complicadores em ITU não complicada e ITU complicada. A ITU é complicada quando estão presentes alterações estruturais ou funcionais do trato urinário ou quando se desenvolve em ambiente hospitalar. Na ITU não complicada a Escherichia coli é a bactéria responsável pela maioria das infecções enquanto nas ITUs complicadas o espectro de bactérias envolvido é bem mais amplo incluindo bactérias Grampositivas e Gram negativas e com elevada frequência organismos multirresistentes. ITU é definida pela presença de 100.000 ufc/mL. Os sinais e sintomas associados à ITU incluem polaciúria, urgência miccional, disúria, hematúria e piúria. A escolha da terapia antimicrobiana para a ITU varia de acordo com a apresentação da infecção, hospedeiro e agente. Estratégias envolvendo diferentes esquemas terapêuticos de acordo com grupos específicos de pacientes maximizam os benefícios terapêuticos, além de reduzir os custos, as incidências de efeitos adversos e o surgimento de microrganismos resistentes.

Urinary Tract Infection (UTI) is one of the most common causes of infection in the general population. Itis more prevalent in females, but also affects male patients especially when associated with manipulation of the urinary tract and prostate disease. The UTI can be classified according to location in lower UTI (cystitis) and high UTI (pyelonephritis) and according the presence of complicating factors in uncomplicated UTI and complicated UTI. The ITU is complicated when structural or functional abnormalities of the urinary tract are present or when it develops in the hospital. In uncomplicated UTI, Escherichia coli is the bacteria responsible for most infections while in complicated UTIs the bacterial spectrum involved is much broader including Gram positive and Gram-negative and high-frequency multi-resistant organisms. UTI is defined by the presence of 100000 cfu/mL. Signs and symptoms associated with UTI include urinary frequency, urinary urgency, dysuria, hematuria and pyuria. The choice of antimicrobial therapy for UTI varies with the presentation of the infection, host and agent. Strategies involving different treatment regimens according to specific patient groups maximize the therapeutic benefits and reduce costs, the incidences of adverse effects and the emergency of resistant organisms.