Elevated adipokines and myokines are associated with fatigue in long COVID patients

BackgroundPersistent fatigue is one of the most common and debilitating symptoms experienced by patients recovering from COVID-19, contributing significantly to the burden of “long COVID” or post-COVID-19syndrome. However, the underlying pathophysiological mechanisms remain inadequately understood. Few studies have examined the association between fatigue and pulmonary or cardiac function, systemic biomarkers, or morphological changes in the lungs and diaphragm. Furthermore, the potential influence of vaccination on the persistence of fatigue has not been fully explored. This study aims to identify mechanisms contributing to post-COVID-19 fatigue.MethodsThis prospective cohort study assessed clinical, laboratory, pulmonary, and cardiac parameters, as well as diaphragm ultrasound and pulmonary function, in patients with and without fatigue at least 4 months after discharge from hospitalization due to COVID-19.ResultsOf 88 patients evaluated, 34% reported new or worsening fatigue after recovering from COVID-19. Demographic characteristics, comorbidities, and vaccination status were similar between fatigued and non-fatigued groups. However, ICU admission during the acute phase of illness emerged as a significant risk factor for fatigue (OR 2.65; 95% CI, 1.03–6.94) in multivariable analysis. No significant differences were observed in lung function, diaphragm or lung ultrasound findings, or left ventricular systolic function between groups. Fatigue was associated with significantly elevated serum levels of myostatin and irisin, markers of muscle metabolism. Additionally, patients experiencing fatigue reported poorer functional capacity and significantly reduced quality of life, with lower scores in multiple domains of the SF-36 questionnaire, including general health, vitality, and mental health.ConclusionPost-COVID-19 fatigue is strongly associated with prior ICU admission and elevated levels of myostatin and irisin, implicating potential myopathic mechanisms in its persistence. The profound impact of fatigue on functional capacity and quality of life highlights the urgent need for further research to elucidate its pathophysiology and develop targeted therapeutic strategies. This study provides critical insights into the interplay between systemic and organ-specific factors contributing to fatigue, offering a foundation for future interventions to improve outcomes in patients with long COVID

Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others

Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives

Since the outbreak of COVID-19 disease, a bidirectional interaction between kidney disease and the progression of COVID-19 has been demonstrated. Kidney disease is an independent risk factor for mortality of patients with COVID-19 as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with COVID-19. However, the detection of kidney damage in patients with COVID-19 may not occur until an advanced stage based on the current clinical blood and urinary examinations. Some studies have pointed out the development of subclinical acute kidney injury (subAKI) syndrome with COVID-19. This syndrome is characterized by significant tubule interstitial injury without changes in the estimated glomerular filtration rate. Despite the complexity of the mechanism(s) underlying the development of subAKI, the involvement of changes in the protein endocytosis machinery in proximal tubule (PT) epithelial cells (PTECs) has been proposed. This paper focuses on the data relating to subAKI and COVID-19 and the role of PTECs and their protein endocytosis machinery in its pathogenesis

SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells

Patients with COVID-19 have high prevalence of albuminuria which is used as a marker of progression of renal disease and is associated with severe COVID-19. We hypothesized that SARS-CoV-2 spike protein (S protein) could modulate albumin handling in proximal tubule epithelial cells (PTECs) and, consequently contribute to the albuminuria observed in patients with COVID-19. In this context, the possible effect of S protein on albumin endocytosis in PTECs was investigated. Two PTEC lines were used: HEK-293A and LLC-PK1. Incubation of both cell types with S protein for 16 h inhibited albumin uptake at the same magnitude. This effect was associated with canonical megalin-mediated albumin endocytosis because: (1) DQ-albumin uptake, a marker of the lyso-somal degradation pathway, was reduced at a similar level compared with fluorescein isothiocyanate (FITC)-albumin uptake; (2) dextran-FITC uptake, a marker of fluid-phase endocytosis, was not changed; (3) cell viability and proliferation were not changed. The inhibitory effect of S protein on albumin uptake was only observed when it was added at the luminal membrane, and it did not involve the ACE2/Ang II/AT1R axis. Although both cells uptake S protein, it does not seem to be required for modulation of albumin endocytosis. The mechanism underlying the inhibition of albumin uptake by S protein encompasses a decrease in megalin expression without changes in megalin trafficking and stability. These results reveal a possible mechanism to explain the albu-minuria observed in patients with COVID-19

Anomalia megadolicobasilar: a propósito de 5 casos diagnosticados angiograficamente

Após breves considerações sobre a sintomatologia e etiopatogenia da megadolicobasilar, são apresentados 5 casos desta anomalia vascular. Concordando com a maioria dos trabalhos sobre o assunto, a idade dos doentes desta série situava-se entre a quarta e sexta décadas da vida, apresentando todos hipertensão arterial de longa duração e aterosclerose avançada; o quadro neurológico deste doentes mostrou-se variável, tendo em comum o fato de ter se iniciado abruptamente. O estudo angiográfico do sistema vértebro-basilar foi o exame que possibilitou o diagnóstico em todos os casos

The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria

1,8-Cineole is a naturally occurring compound found in essential oils of different plants and has well-known anti-inflammatory and antimicrobial activities. In the present work, we aimed to investigate its potential antimalarial effect, using the following experimental models: (1) the erythrocytic cycle of Plasmodium falciparum; (2) an adhesion assay using brain microvascular endothelial cells; and (3) an experimental cerebral malaria animal model induced by Plasmodium berghei ANKA infection in susceptible mice. Using the erythrocytic cycle of Plasmodium falciparum, we characterized the schizonticidal effect of 1,8-cineole. This compound decreased parasitemia in a dose-dependent manner with a half maximal inhibitory concentration of 1045.53 ± 63.30 μM. The inhibitory effect of 972 μM 1,8-cineole was irreversible and independent of parasitemia. Moreover, 1,8-cineole reduced the progression of intracellular development of the parasite over 2 cycles, inducing important morphological changes. Ultrastructure analysis revealed a massive loss of integrity of endomembranes and hemozoin crystals in infected erythrocytes treated with 1,8-cineole. The monoterpene reduced the adhesion index of infected erythrocytes to brain microvascular endothelial cells by 60%. Using the experimental cerebral malaria model, treatment of infected mice for 6 consecutive days with 100 mg/kg/day 1,8-cineole reduced cerebral edema with a 50% reduction in parasitemia. Our data suggest a potential antimalarial effect of 1,8-cineole with an impact on the parasite erythrocytic cycle and severe disease.</jats:p