The Impact of Pathogens on Sepsis Prevalence and Outcome

Abstract

Sepsis, a severe global healthcare challenge, is characterized by significant morbidity and mortality. The 2016 redefinition by the Third International Consensus Definitions Task Force emphasizes its complexity as a "life-threatening organ dysfunction caused by a dysregulated host response to infection". Bacterial pathogens, historically dominant, exhibit geographic variations, influencing healthcare strategies. The intricate dynamics of bacterial immunity involve recognizing pathogen-associated molecular patterns, triggering innate immune responses and inflammatory cascades. Dysregulation leads to immunothrombosis, disseminated intravascular coagulation, and mitochondrial dysfunction, contributing to the septic state. Viral sepsis, historically less prevalent, saw a paradigm shift during the COVID-19 pandemic, underscoring the need to understand the immunological response. Retinoic acid-inducible gene I-like receptors and Toll-like receptors play pivotal roles, and the cytokine storm in COVID-19 differs from bacterial sepsis. Latent viruses like human cytomegalovirus impact sepsis by reactivating during the immunosuppressive phases. Challenges in sepsis management include rapid pathogen identification, antibiotic resistance monitoring, and balancing therapy beyond antibiotics. This review highlights the evolving sepsis landscape, emphasizing the need for pathogen-specific therapeutic developments in a dynamic and heterogeneous clinical setting.

Keywords: COVID-19; bacteria; immunity; sepsis; virus.

Figure 1

Pathogen prevalence in positive isolates in different cohorts over time, based on the publications of Vincent et al. 2006 [12], Moreno et al. 2008 [13], and Umemura et al. 2021 [8].

Figure 2

Simplified immune response during sepsis upon infection with a pathogen. Created with BioRender.com. PAMP = pathogen-associated molecular pattern; PRR = pattern-recognition receptor; DAMP = damage-associated molecular pattern; ROS = reactive oxygen species; NETosis = neutrophil extracellular trap formation; DIC = disseminated intravascular coagulation; ARDS = Acute Respiratory Distress Syndrome; MODS = Multiple Organ Dysfunction Syndrome; CRP = C-reactive protein, red upward arrow indicate elevated concentration.