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. 2023 Apr;29(3):415-429.
doi: 10.1111/jep.13772. Epub 2022 Sep 28.

Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology

Felix Tretter  1 , Eva M J Peters  2   3 , Joachim Sturmberg  4   5 , Jeanette Bennett  6 , Eberhard Voit  7 , Johannes W Dietrich  8   9   10   11 , Gary Smith  12 , Wolfram Weckwerth  13 , Zvi Grossman  14 , Olaf Wolkenhauer  15 , James A Marcum  16
Affiliations

Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology

Felix Tretter et al. J Eval Clin Pract. 2023 Apr.

Abstract

Is data-driven analysis sufficient for understanding the COVID-19 pandemic and for justifying public health regulations? In this paper, we argue that such analysis is insufficient. Rather what is needed is the identification and implementation of over-arching hypothesis-related and/or theory-based rationales to conduct effective SARS-CoV2/COVID-19 (Corona) research. To that end, we analyse and compare several published recommendations for conceptual and methodological frameworks in medical research (e.g., public health, preventive medicine and health promotion) to current research approaches in medical Corona research. Although there were several efforts published in the literature to develop integrative conceptual frameworks before the COVID-19 pandemic, such as social ecology for public health issues and systems thinking in health care, only a few attempts to utilize these concepts can be found in medical Corona research. For this reason, we propose nested and integrative systemic modelling approaches to understand Corona pandemic and Corona pathology. We conclude that institutional efforts for knowledge integration and systemic thinking, but also for integrated science, are urgently needed to avoid or mitigate future pandemics and to resolve infection pathology.

Keywords: integrative systems pathology of Corona; methodology of systemic modelling; social ecology of pandemics; systems science and thinking.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A socioecological multi‐level systems model—from the whole to the parts and back with particular nested systems models (adopted and modified from Sturmberg and Martin).
Figure 2
Figure 2
Physiological macroscopic multi‐compartment and multi‐level model of the organismic response to respiratory virus infection, along with stages of the viral invasion process, with conditions and reactions associated with affected compartments (modified from Tretter et al.).
Figure 3
Figure 3
Hypothetical qualitative model of the basic cellular network guiding the host's defence to SARS‐CoV2 infection, possibly leading to a persistent hyperinflammatory state. The cause may be a pernicious cycle of (1) ongoing asymmetric reciprocal inhibition (antagonism) between pro‐inflammatory and anti‐inflammatory immune responses to the virus (top panel) and (2) reciprocal synergistic actions within the affected systems. ACE, angiotensin‐converting enzyme 2; AntiI‐IS, anti‐inflammatory immune system; ATII angiotensin II, AT1R, angiotensin 1 receptor; Mas‐R, MAS (G‐protein‐coupled) receptor, MP1, macrophage 1, MP2, macrophage 2; ProI‐IS, pro‐inflammatory immune system; RAAS, renin–angiotensin/aldosterone system; TH1, T‐helper cell 1, TH2, T‐helper cell 12, Il‐4, IFN, TNF, IL‐10, cytokines.
Figure 4
Figure 4
Heuristic models of disease in the format of coupled pendula that focus on the relative functional dominance of a subsystem. (A) CNS functions and mental disorders (e.g., depression, schizophrenia and alcoholism) as consequences of different neurotransmitter imbalances with relative hypofunction of biogenic amines and relative hyperfunction of other transmitter systems. (B) The immune system in a pro‐inflammatory state that is characterized by dominance of macrophages with MP1 over MP2 and T‐helper cells with TH1 over TH2. (C) Integrative pendulum model of the nervous system, the endocrine system and the immune system. For Figure 2; COR, Cortisol; SNS, sympathetic nervous system; PNS, parasympathetic nervous system.
Figure 5
Figure 5
The Janus‐faced role of interferons and a competition of positive and negative feedback loops determine the course of COVID‐19 infection. After binding to ACE‐2, SARS‐Cov2 is able to enter cells and to replicate. This initiates immune responses via B and T cells and interferon release, thereby reducing the virus load again. However, interferon alpha also stimulates the expression of ACE‐2, which facilitates virus entry and implements a positive feedback loop raising the global virus load.
Figure 6
Figure 6
Higher expression of the transmembrane serine protease 2 (TMPRSS2), as observed, for example, in males, stimulates the binding of SARS‐CoV2 to the ACE receptor and promotes a higher virus load. Simulation of the motif of combined positive and negative feedback loops as outlined in Figure 3 suggests that higher TMPRSS2 expression may also give rise to oscillatory dynamics of the virus load, as previously observed in severe cases of COVID‐19.
See this image and copyright information in PMC

References

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