The Plasma Proteome in Community-acquired Pneumonia: Pathophysiology, Outcome, and 10-Year Risk

Abstract Rationale Community-acquired pneumonia (CAP) represents a significant health burden. Objectives We aimed to map the plasma proteome in patients with CAP and associate protein abundance with pathophysiology, tissue source, and outcome. Methods We measured the plasma proteome of patients with CAP upon admission to a general ward using Olink technology (derivation cohort). Additional Olink measurements were performed in patients with CAP admitted to the ICU and patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia across care settings (validation cohorts). Measurements and Main Results Of 2,676 proteins analyzed in 93 ward patients with CAP and 21 healthy control subjects, 904 (33.8%) were higher in CAP, 396 (14.8%) lower, and 1,376 (51.4%) not different. More abundant proteins were associated with innate immune and mitosis pathways and mainly originated from lung and cardiac tissue. A total of 131 proteins associated with time to clinical stability (TCS), of which 124 (primarily related to monocyte and macrophage and RNA processing) were connected with a long TCS. Most TCS-associated proteins were differentially abundant in nonsurvivors versus survivors among 88 patients with ICU-CAP (1.4- to 3.5-fold higher) and 305 patients with SARS-CoV-2 pneumonia (1.16- to 1.35-fold lower or 1.14- to 2.65-fold higher; all P < 0.05). In the general population (UK Biobank), 115 of 124 (92.7%) proteins correlated with long TCS were associated with an increased risk of pneumonia during a 10-year follow-up, whereas 6 of 7 (85.7%) proteins correlated with shorter TCS were associated with a lower risk of pneumonia. Conclusions This now publicly available CAP plasma proteome provides information on pathophysiological mechanisms and tissue involvement and may support development of personalized therapies.