Revisiting Metchnikoff's work in light of the COVID-19 pandemic illustrates how much this amazing scientist was a polymath, and one could speculate how much he would have been fascinated and most interested in following the course of the pandemic. Since he coined the word "gerontology", he would have been intrigued by the high mortality among the elderly, and by the concepts of immunosenescence and inflammaging that characterize the SARS-CoV-2 infection. While Metchnikoff's work is mainly associated with the discovery of the phagocytes and the birth of cellular innate immunity, he regularly invited his closest collaborators to investigate humoral immunity, and it was in his laboratory that Jules Bordet made his major discovery of the complement system. While Metchnikoff and his team investigated many infectious diseases, he also contributed to studies linked to vaccination, such as those on typhoid fever performed in chimpanzees, illustrating that non-human primates can provide animal models which are potentially helpful for understanding the pathophysiology of the COVID-19 virus. In the present review, we illustrate how much his own work and the investigations of his trainees were pertinent to this new disease.

BACKGROUND:Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. OBJECTIVE:To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. METHODS:A total of 31 experts from 13 countries participated and were divided into 6 thematic working groups (WG): (1) study design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction, (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013). RESULTS:Overall, the participants reached consensus on 29 points; 20 at "recommendation" (R) and 9 at "consideration" (C) strength. This executive summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2, and 3). Detailed commentaries to all Rs and Cs are simultaneously published in three separate full-length papers. CONCLUSIONS:We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The goal of the conference was to identify limitations of preclinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Preclinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into six thematic Working Groups: Study Design, Humane modeling, Infection types, Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013). Overall, the participants reached consensus on 29 points; 20 at "recommendation" and nine at "consideration" strength. This Executive Summary provides a synopsis of the MQTiPSS consensus. We believe that these recommendations and considerations will serve to bring a level of standardization to preclinical models of sepsis and ultimately improve translation of preclinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.

Purpose

Pre-clinical animal studies precede the majority of clinical trials. While the clinical sepsis definitions and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May, 2017. The conference goal was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models.

Methods

31 experts from 13 countries participated and were divided into 6 thematic Working Groups (WG): (1) Study Design, (2) Humane modeling, (3) Infection types, (4) Organ failure/dysfunction, (5) Fluid resuscitation and (6) Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013).

Results

Overall, the participants reached consensus on 29 points; 20 at "recommendation" (R) and 9 at "consideration" (C) strength. This Executive Summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2 and 3).

Conclusions

We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as "best practices" that should be implemented for animal sepsis models. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

The original version of this article unfortunately contained mistakes.