ABSTRACT
Background: Although COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and associate with long-term respiratory dysfunction is unknown. Methods: From the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition (Fig. 1), with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being 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 three months. Figure 1 legend: Gut microbial composition in patients with respiratory dysfunction at the three-month follow-up (DLCO<="" div=""> Conclusion: Respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.
ABSTRACT
Background: There are conflicting results regarding impaired cardiac function in patients that have recovered from COVID-19. Cardiovascular magnetic resonance (CMR) studies have revealed a very high frequency of cardiac involvement (78%) and ongoing myocardial inflammation (60%) in patients recently recovered from COVID-19. Findings are advocating further investigation of the long-term myocardial consequences of COVID-19 disease. Purpose: We aimed to investigate left ventricular (LV) and right ventricular (RV) function by a comprehensive echocardiographic study in patients recovered from COVID-19 infection 3 months after admission to hospital. Methods: All patients (n=92) had been hospitalized for COVID-19 and were examined with echocardiography three months after hospitalization. They were 59±13 years, and 43% were women. LV function was assessed by ejection fraction (EF) and global longitudinal strain (GLS) and RV function was measured by fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE) and RV GLS free wall. Tricuspid regurgitation pressure gradient was measured to estimate pulmonary artery pressure. Results: LV EF was 63±6% and LV GLS was -18.6±2.2%. All patients had normal EF >53%, but 10 showed signs of subtle impaired LV function by LV GLS (≥ -16%). Only two of these did not have hypertension, LV hypertrophy, diabetes or other preexisting diagnosis of heart disease explaining subtle LV dysfunction. All had normal RV FAC (48±7%) and TAPSE (2.3±0.3 cm). We found modestly impaired RV longitudinal function (RV GLS free wall >-25%) in 30% patients, but none had RV GLS worse than -20%. One-third of all patients with reduced RV GLS had signs of elevated pulmonary arterial pressures, which might impact the assessment of RV function. Conclusions: Traditional echocardiographic parameters showed normal function in all hospitalized COVID-19 patients three months after hospital admittance. Approximately one-third had subtle ventricular dysfunction detected by sensitive echocardiographic methods, but these findings could mostly be explained by systemic or pulmonary hypertension. We cannot, however, exclude that a slight reduction in cardiac function in a minority of our patients was caused by the COVID-19 infection.
ABSTRACT
BACKGROUND: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID-19 patients. METHODS: Plasma levels of a gut leakage marker (LPS-binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL-1ß, IL-18 and their regulatory proteins) were measured at three time points (day 1, 3-5 and 7-10) in 39 hospitalized COVID-19 patients and related to cardiac involvement. RESULTS: Compared to controls, COVID-19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT-pro-BNP levels, whereas IL-18, IL-18BP and IL-1Ra were associated with higher troponin levels. CONCLUSION: Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut-heart axis in COVID-19.