Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. METHODS: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene. RESULTS: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months. CONCLUSION: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life. Pentraxin 3 (PTX3) is an essential component of innate immunity and independently associated with the risk of developing vascular events. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma PTX3 in pregnancy and at 5 years after the index pregnancy. METHODS: This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting PTX3 levels were measured four times during pregnancy and at follow-up. RESULTS: PTX3 levels were lower early in pregnancy and at 5 years follow-up in women who developed GDM. PTX3 levels throughout pregnancy were associated with body mass index. Low PTX3 levels in early pregnancy were predictive of an increased apoB/apoA ratio at 5-year follow-up. PTX3 at 5-year follow-up was inversely correlated with multiple metabolic risk factors for CVD, including body composition, arterial stiffness, dyslipidemia and previous GDM. CONCLUSIONS: Our results show that low plasma concentration of PTX3 in early pregnancy is associated with subsequent development of GDM and with an enhanced risk for CVD as estimated by an elevated apoB/apoA ratio at 5 years postpartum.