Skeletal muscle-related symptoms are common in both acute coronavirus disease (Covid)-19 and post-acute sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post-viral fatigue syndrome. Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post-intensive care unit (ICU) syndrome and ICU-acquired weakness and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS-CoV-2-specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid-19 and PASC.
BACKGROUND: Findings on the association between early high protein provision and mortality in ICU patients are inconsistent. The relation between early high protein provision and mortality in patients receiving CRRT remains unclear. The aim was to study the association between early high protein provision and hospital and ICU mortality and consistency in subgroups.METHODS: A retrospective cohort study was conducted in 2618 ICU patients with a feeding tube and mechanically ventilated ≥48 h (2003-2016). The association between early high protein provision (≥1.2 g/kg/day at day 4 vs. <1.2 g/kg/day) and hospital and ICU mortality was assessed for the total group, for patients receiving CRRT, and for non-septic and septic patients, by Cox proportional hazards analysis. Adjustments were made for APACHE II score, energy provision, BMI, and age.RESULTS: Mean protein provision at day 4 was 0.96 ± 0.48 g/kg/day. A significant association between early high protein provision and lower hospital mortality was found in the total group (HR 0.48, 95% CI 0.39-0.60, p = <0.001), CRRT-receiving patients (HR 0.62, 95% CI 0.39-0.99, p = 0.045) and non-septic patients (HR 0.56, 95% CI 0.44-0.71, p = <0.001). However, no association was found in septic patients (HR 0.71, 95% CI 0.39-1.29, p = 0.264). These associations were very similar for ICU mortality. In a sensitivity analysis for patients receiving a relative energy provision >50%, results remained robust in all groups except for patients receiving CRRT.CONCLUSIONS: Early high protein provision is associated with lower hospital and ICU mortality in ICU patients, including CRRT-receiving patients. There was no association for septic patients.
Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensivephylogenetic and intron position analyses. We found that mammalian intramitochondrial CPT2 is most closely related to cytosolic yeast carnitine transferases (Sc-YAT1 and 2), whereas the other members of the family are related to intraorganellar yeast Sc-CAT2. Therefore, the cytosolically active CPT1 more closely resembles intramitochondrial ancestors than CPT2. The choline acetyltransferase is closely related to carnitine acetyltransferase and shows lower evolutionary rates than long chain acyltransferases. In the CPT1 family several duplications occurred during animal radiation, leading to the isoforms CPT1A, CPT1B and CPT1C. In addition, we found five CPT1-like genes in Caenorhabditis elegans that strongly group to the CPT1 family. The long branch leading to mammalian brain isoform CPT1C suggests that either strong positive or relaxed evolution has taken place on this node. The presented evolutionary delineation of carnitine/choline acyltransferases adds to current knowledge on their functions and provides tangible leads for further experimental research.
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