PARIS (Pneumonia: Acute Respiratory Infection +/- Sepsis): a prospective single-centre observational cohort study of hospitalised patients with pneumonia

Introduction Hospitalised community-acquired pneumonia (CAP) is heterogeneous in aetiology, severity, and outcome. Phenotyping and endotyping approaches offer potential to stratify patients biologically and guide targeted therapy, but require well-characterised cohorts with linked biosamples. We describe the PARIS (Pneumonia: Acute Respiratory Infection +/- Sepsis) study: a prospective observational cohort of hospitalised patients with pneumonia, designed to characterise functional outcomes and to provide a biobank for translational immunological research. Methods Adults admitted with CAP to a single NHS district general hospital were enrolled within 24 hours of admission between December 2020 and March 2022. Clinical, functional, and physiological data were collected at enrolment, hospital discharge, and 6-8 week follow-up. Serial blood samples were collected for flow cytometry, transcriptomics, pathogen DNA detection, and plasma biobanking. Results Forty-seven patients were enrolled (15 without and 32 with sepsis [SOFA >=2] at enrolment); 87% met sepsis criteria by 24 hours post enrolment. Most patients (30/47, 64%) were managed as COVID-19, microbiologically confirmed in 27. Mean age was 57 years (SD 16), 70% were male, and baseline comorbidity burden was low. Severity was moderate (median NEWS2 4 at enrolment, rising to 6 by 24 hours post enrolment; p<0.001). Mortality was 4/47 (8.5%), with 44/47 (94%) alive at hospital discharge. Median length of stay was 8 days (IQR 5.5-11). Translational samples were collected from the majority: fresh flow cytometry (44/47, 94%), transcriptomics from the sepsis subgroup (31/32, 97%), pathogen DNA sampling (35 samples received across study timepoints; see Table 5), and stored plasma (29/47, 62%). The primary outcome of functional decline (Barthel score decrease >=1.85) occurred in only 1/29 patients with paired assessments (3.4%). Persistent CRP elevation (>3 mg/L) at 6-8 week follow-up was present in 16/31 (52%) survivors with available data. Conclusions The PARIS cohort provides a well-characterised clinical platform and linked biobank to support translational studies of pneumonia and sepsis. The low rate of functional decline reflects the younger, lower-comorbidity, COVID-predominant population recruited. Primary protocol endpoints were not achieved owing to pandemic-related disruption. Data and samples underpin a programme of linked translational studies.