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COVID-19 has been associated with having a negative impact on patients' gut microbiome during both active disease and in the post-acute phase. In acute COVID-19, rapid alteration of the gut microbiome composition was observed, showing on one side a reduction in beneficial symbionts (e.g., Roseburia, Lachnospiraceae) and on the other side an increase in opportunistic pathogens such as Enterococcus and Proteobacteria. Alpha diversity tends to decrease, especially initially with symptom onset and hospital admission. Although clinical recovery appears to align with improved gut homeostasis, this process could take several weeks, even in mild infections. Moreover, patients with COVID-19 post-acute syndrome showed changes in gut microbiome composition, with specific signatures associated with decreased respiratory function up to 12 months following acute disease. Potential treatments, especially probiotic-based therapy, are under investigation. Open questions remain on the possibility to use gut microbiome data to predict disease progression and on potential confounders that may impair result interpretation (e.g., concomitant therapies in the acute phase; reinfection, vaccines, and occurrence of novel conditions or diseases in the post-acute syndrome). Understanding the relationships between gut microbiome dynamics and disease progression may contribute to better understanding post-COVID syndrome pathogenesis or inform personalized treatment that can affect specific targets or microbiome markers.
RESUMEN
INTRODUCTION: To better define COVID-19 long-term impact we prospectively analysed patient-centred outcomes, including general health and symptom duration. METHODS: Barthel index (BI), St. George's Respiratory Questionnaire adapted to patients with COVID-19 (aSGRQ) and WHO Clinical Progression Scale (CPS) were measured at enrolment and at 6 weeks from the onset of symptoms. Persistence of most frequently reported symptoms was assessed at 6 weeks and, among symptomatic patients, at 12 weeks from the onset of symptoms. Predictors of impaired general health over time were identified using an ordinal multilevel multivariate model. RESULTS: A total of 448 patients (55% men, median age 56 years) were enrolled. WHO-CPS showed mild, moderate and severe disease in 48%, 42% and 10% of patients at admission and mild disease in all patients at follow-up, respectively. BI and aSGRQ were normal in 96% and 93% patients before COVID-19 but only in 47% and 16% at COVID-19 diagnosis and in 87% and 65% at 6-week follow-up. Male gender was identified by all three assessments as a predictor of impaired general health (BI, OR 2.14, p < 0.0001; aSGRQ, OR 0.53, p = 0.003; WHO-CPS, OR 1.56, p = 0.01). Other predictors included age, ICU admission and comorbidities (e.g. cardiovascular disease and cancer) for BI, hospital admission for aSGRQ, age and presence of comorbidities for WHO-CPS. At 6- and 12-week follow-up, 39% and 20% of patients, respectively, were still reporting symptoms. Fatigue and breathlessness were the most frequently reported symptoms. CONCLUSIONS: Long-term follow-up facilitates the monitoring of health impairment and symptom persistence and can contribute to plan tailored interventions.
RESUMEN
Adhesion G protein-coupled receptors (aGPCRs) comprise the second largest yet least studied class of the GPCR superfamily. aGPCRs are involved in many developmental processes and immune and synaptic functions, but the mode of their signal transduction is unclear. Here, we show that a short peptide sequence (termed the Stachel sequence) within the ectodomain of two aGPCRs (GPR126 and GPR133) functions as a tethered agonist. Upon structural changes within the receptor ectodomain, this intramolecular agonist is exposed to the seven-transmembrane helix domain, which triggers G protein activation. Our studies show high specificity of a given Stachel sequence for its receptor. Finally, the function of Gpr126 is abrogated in zebrafish with a mutated Stachel sequence, and signaling is restored in hypomorphic gpr126 zebrafish mutants upon exogenous Stachel peptide application. These findings illuminate a mode of aGPCR activation and may prompt the development of specific ligands for this currently untargeted GPCR family.
