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 > 2 mg/dL, congestive heart failure, vegetation length > 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.

Molnupiravir is an oral agent a metabolite of which has activity against SARS-CoV-2. In a controlled trial in adults hospitalized for Covid-19 who had symptoms for 10 days or less prior to randomization, patients received placebo (n=75) or varying doses of molnupiravir (n=218) administered twice-daily for 5 days. There was no impact of treatment on death. Median time to sustained recovery was 9 days in all groups, with day 29 recovery rates ranging from 81.5%-85.2%. There were no dose-limiting side effects or adverse events.

The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection.

Background: Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes. Methods: We conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. IgG antibody titer was evaluated by ELISA against the S2 subunit, the receptor binding domain (RBD), and the nucleoprotein (NP). Statistical analyses were carried out using mixed-effects models. Findings: We found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity, which persisted 6 months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a 2-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at 6 months remained higher among hospitalized individuals compared to mild symptomatic. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of anti-RBD, S2, or NP antibody titers, all of them showing a constant decline over the follow-up period. Conclusions: Our results reinforce the hypothesis that the quality of the neutralizing immune response against SARS-CoV-2 evolves over the post-convalescent stage.

Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.