Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Unexpected persistence of extended-spectrum β-lactamase-producing Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with imipenem

Imipenem is active against extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) but favours the intestinal emergence of resistance. The effects of imipenem on intestinal microbiota have been studied using culture-based techniques. In this study, the effects were investigated in patients using culture and metagenomic techniques. Seventeen hospitalised adults receiving imipenem were included in a multicentre study (NCT01703299, http://www.clinicaltrials.gov). Most patients had a history of antibiotic use and/or hospitalisation. Stools were collected before, during and after imipenem treatment. Bacterial and fungal colonisation was assessed by culture, and microbiota changes were assessed using metagenomics. Unexpectedly, high colonisation rates by imipenem-susceptible ESBL-E before treatment (70.6%) remained stable over time, suggesting that imipenem intestinal concentrations were very low. Carriage rates of carbapenem-resistant Gram-negative bacilli (0-25.0%) were also stable over time, whereas those of yeasts (64.7% before treatment) peaked at 76.5% during treatment and decreased thereafter. However, these trends were not statistically significant. Yeasts included highly diverse colonising Candida spp. Metagenomics showed no global effect of imipenem on the bacterial taxonomic profiles at the sequencing depth used but demonstrated specific changes in the microbiota not detected with culture, attributed to factors other than imipenem, including sampling site or treatment with other antibiotics. In conclusion, culture and metagenomics were highly complementary in characterising the faecal microbiota of patients. The changes observed during imipenem treatment were unexpectedly limited, possibly because the microbiota was already disturbed by previous antibiotic exposure or hospitalisation

Impact of Antibiotic Gut Exposure on the Temporal Changes in Microbiome Diversity

Although the global deleterious impact of antibiotics on the intestinal microbiota is well known, temporal changes in microbial diversity during and after an antibiotic treatment are still poorly characterized. We used plasma and fecal samples collected frequently during treatment and up to one month after from 22 healthy volunteers assigned to a 5-day treatment by moxifloxacin ( n  = 14) or no intervention ( n  = 8). </jats:p

Characteristics, management, and outcomes of patients with left-sided infective endocarditis complicated by heart failure: a substudy of the ESC-EORP EURO-ENDO (European infective endocarditis) registry

Aims: To evaluate the current management and survival of patients with left-sided infective endocarditis (IE) complicated by congestive heart failure (CHF) in the ESC-EORP European Endocarditis (EURO-ENDO) registry. Methods and results: Among the 3116 patients enrolled in this prospective registry, 2449 (mean age: 60years, 69% male) with left-sided (native or prosthetic) IE were included in this study. Patients with CHF (n&nbsp;=&nbsp;698, 28.5%) were older, with more comorbidity and more severe valvular damage (mitro-aortic involvement, vegetations &gt;10 mm and severe regurgitation/new prosthesis dehiscence) than those without CHF (all p ≤ 0.019). Patients with CHF experienced higher 30-day and 1-year mortality than those without (20.5% vs. 9.0% and 36.1% vs. 19.3%, respectively) and CHF remained strongly associated with 30-day (odds ratio[OR] 2.37, 95% confidence interval [CI] [1.73-3.24; p &lt; 0.001) and 1-year mortality (hazard ratio [HR] 1.69, 95% CI 1.39-2.05; p &lt; 0.001) after adjustment for established outcome predictors, including early surgery, or after propensity matching for age, sex, and comorbidity (n&nbsp;=&nbsp;618 [88.5%] for each group, both p &lt; 0.001). Early surgery, performed on 49% of these patients with IE complicated by CHF, remained associated with a substantial reduction in 30-day mortality following multivariable analysis, after adjustment for age, sex, Charlson comorbidity index, cerebrovascular accident, Staphylococcus aureus IE, streptococcal IE, uncontrolled infection, vegetation size &gt;10 mm, severe valvular regurgitation and/or new prosthetic dehiscence, perivalvular complication, and prosthetic IE (OR 0.22, 95% CI 0.12-0.38; p &lt; 0.001) and in 1-year mortality (HR 0.29, 95% CI 0.20-0.41; p &lt; 0.001). Conclusion: Congestive heart failure is common in left-sided IE and is associated with older age, greater comorbidity, more advanced lesions, and markedly higher 30-day and 1-year mortality. Early surgery is strongly associated with lower mortality but is performed on only approximately half of patients with CHF, mainly because of a surgical risk considered prohibitive

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry

Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results: As compared to &lt; 80&nbsp;yo patients, ≥ 80&nbsp;yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p &lt; 0.001), of surgery performed (37.0% vs. 75.5%, p &lt; 0.001), and a higher in-hospital (25.9% vs. 15.8%, p &lt; 0.001) and 1-year mortality (41.3% vs. 22.2%, p &lt; 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43-3.66]). By propensity analysis, 304 ≥ 80&nbsp;yo were matched to 608 &lt; 80&nbsp;yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p &lt; 0.0001) in ≥ 80&nbsp;yo. Overall mortality remained higher in ≥ 80&nbsp;yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of &lt; 80&nbsp;yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion: Although mortality rates are consistently higher in ≥ 80&nbsp;yo patients than in &lt; 80&nbsp;yo patients in the general population, mortality of surgery in ≥ 80&nbsp;yo is similar to &lt; 80&nbsp;yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80&nbsp;yo patients

The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry

The European Society of cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of infective endocarditis and data from the 2001 Euro Heart Survey

Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study

The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). AIMS: The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). METHODS AND RESULTS: Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine &gt; 2 mg/dL, congestive heart failure, vegetation length &gt; 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. CONCLUSION: Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles