Pneumonia, which can be acquired in the community (including influenza and COVID-19), is a leading cause of mortality. The risk of severe cardiovascular diseases events (stroke, myocardial infarction, pulmonary embolism) increases after infections, but causal mechanisms are not understood yet. There is an essential need for improved understanding of the relationship between pneumonia and cardiovascular diseases and early identification of patients at risk of cardiovascular events to develop tailored therapies.
The overall concept underpinning "Homi-lung" is to investigate the time course of host-microbiome interactions during \& after pneumonia to i) understand the causal relationship between trained immunity, microbiome dysbiosis and cardiovascular and respiratory diseases (CVRD) progressions, ii) define endotypes of pneumonia associated with response to treatment \& CVRD history; iii) develop biomarkers to predict the individual response to the treatment \& CVRD progression, and iv) preclinically validate therapeutical approaches for CVRD during \& after pneumonia.
Adults (18 years or more) of both genders (Female/Male: 50/50 ratio)
No history of severe pneumonia (sCAP, COVID-19 or HAP)
Presence of no or one of the following comorbidities: obesity (defined as body mass index over 35 kg/m2), type 2 diabetes mellitus, hypercholesterolemia, essential arterial hypertension, or familial history of CVD.
Adults (18 years or more) of both genders (Female/Male ratio: 50/50)
Presence of two or more comorbidities
Any other co-existing disorder generating CVRD symptoms
Limited chance of survival for at least six months due to co-existing comorbidity (-ies) according to the judgement of the attending physicians
Pregnancy or lactation
The study needs to enroll four groups of patients to cover the magnitude of the spectrum of community-acquired pneumonia and enroll the required controls: * Group A: Controls with no or one comorbidity, predisposing to significant CV events and without a medical history of severe pneumonia. This group is important to provide baseline biological values and control samples to investigate normal host-microbiome interactions. No follow-up is performed for healthy controls. * Group B: Controls with comorbidities predisposing to major CV events and without a medical history of severe pneumonia. This group is important to provide normal CVRD progression in patients at risk and control samples for the investigation of host-microbiome interactions in patients with stable CVRD. * Group C: Patients cured of acute COVID-19. * Group D: Patients cured of severe community-acquired pneumonia.
Other
Cross-sectional
Blood samples and Oropharyngeal swab
Other interventionBlood samples: EDTA-plasma (proteome, metabolome and lipidome) and PBMCs (transcriptome, epigenome, immune-phenotype and genetic polymorphism)
Six-minute walk test, Spirometry, ECG, Heart ultrasound and cardiopulmonary exercise stress testing, Completion of questionnaires of symptoms
Other intervention* Spirometry for forced expiratory volume in the first, second, total lung capacity and diffusion capacity of carbon monoxide. * ECG, Heart ultrasound and cardiopulmonary exercise stress testing: * NYHA * Rhythm or conduction abnormality (yes/no) * Left ventricular ejection fraction (%) * VO2Max
The first primary outcome is the rates of major cardiovascular disease event at 6 months.
Major CVD events are all-cause mortality, stroke, non-fatal acute coronary syndrome, pulmonary embolism or venous thrombosis
The second primary endpoint is poor cardiorespiratory fitness at 36 months.
Poor fitness is a VO2max lower than normal values for age.
Rates of unplanned hospitalisation
Rates of unplanned hospitalisation
Rates of COPD exacerbation, hospitalization for respiratory failure and/or respiratory-related mortality at 3 years
Rates of COPD exacerbation, hospitalization for respiratory failure and/or respiratory-related mortality at 3 years
Rates of secondary episodes of pneumonia, the incidence of non-respiratory infections
Rates of secondary episodes of pneumonia, the incidence of non-respiratory infections
The rates of major cardiovascular disease event and of poor cardiorespiratory fitness
The rates of major cardiovascular disease event at 6 months and of poor cardiorespiratory fitness at 36 months according to the microbiology of sCAP (viral vs bacterial vs mixed etiology)
Click on the lead sponsor to view all of their trials.
