Sepsis and COVID-19: Cross-Talk in Signalling Pathways and in Therapeutic Perspectives

About this Research Topic

Background

Sepsis, as a manifestation of several endemic and epidemic diseases, has had a profound impact on humankind's history. One of the most illustrative examples is the plague epidemic which, in its septicemic form, decimated a third of the European population in the 14th century.
In the last decades, sepsis remained a major cause of morbidity and mortality worldwide. Evaluating sepsis-related deaths among the underlying causes of deaths in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), 2017, Rudd and coworkers estimated that 48·9 incident cases of sepsis were recorded worldwide and 11·0 million sepsis-related deaths were reported, representing 19·7%  of all global deaths.
In 2020 the world was challenged by COVID-19 pandemic. Just a year ago, in December 2019, the city of Wuhan, in China, became the center of an outbreak of pneumonia of unknown cause, rapidly identified as caused by a new coronavirus, the SARS-CoV-2 (from “severe acute respiratory syndrome coronavirus 2”). The disease was characterized as COVID-19 (an acronym for "coronavirus disease") by the World Health Organization (WHO) on February 11, 2020, and in just a month, on March 11, was declared as a global pandemic (WHO Director-General’s opening remarks at the media briefing on COVID19 -March 2020). As of December, 5th, 2020, COVID-19 confirmed cases exceed 65 million leading to 1.5 million deaths (https://covid19.who.int).
Pathogenesis of sepsis and COVID-19 converges to a pivotal role of host inflammatory response. Sepsis was first described as a “systemic inflammatory response syndrome triggered by infection” (Sepsis-1) and evolved to “a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection” (Sepsis-3), encompassing the huge progress in understanding the complexity of host response in sepsis and the multiple disruptions in metabolic and immune functions achieved in the time elapsed between these two definitions. Mechanisms of COVID-19 disease resemble those of sepsis, and indeed, COVID-19 is a viral sepsis. Cytokines storm, procoagulant state, Toll-Like Receptor (TLR) signaling, Pathogen-associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs), neutrophil extracellular traps (NETs), inflammasome, changes in lipids profile, the sepsis literature quickly became COVID literature as well. The pathogenesis-oriented target therapy also converges sepsis and COVID-19. In sepsis, new clinical trials design and approaches to reduce heterogeneity of patients coupled with new therapeutic targets are among the strategies to circumvent the frustrating history of adjuvant therapy in the field. In COVID-19, as was formerly the case with sepsis, a great enthusiasm was observed with multiple inflammation-based targets for intervention, the IL-6 inhibitors as an illustrating example. Again, deciphering the host-protective defense from the harmful response is a pivotal research challenge. For both, sepsis and COVID-19, cancer derived research is a source of reference.
In this Frontiers in Medicine Research Topic our goal is to present the current progress and perspectives regarding epidemiology, pathogenesis and therapy research in sepsis and COVID-19 with in the hope to provide a fruitful platform for converging knowledge and experiences in these challenging diseases.
We welcome manuscripts in Frontiers in Medicine accepted formats, including original research, systematic reviews, reviews, mini reviews, perspectives, clinical trials and case reports.

Keywords: Sepsis, Covid-19, Sepsis and Covid, cytokines, inflammatory response, coagulation, PAMP, DAMP, pathogenesis, therapeutic interventions

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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