Physiological Network Is Disrupted in Severe COVID-19

Abstract

The human body is a complex system maintained in homeostasis thanks to the interactions between multiple physiological regulation systems. When faced with physical or biological perturbations, this system must react by keeping a balance between adaptability and robustness. The SARS-COV-2 virus infection poses an immune system challenge that tests the organism’s homeostatic response. Notably, the elderly and men are particularly vulnerable to severe disease, poor outcomes, and death. Mexico seems to have more infected young men than anywhere else. The goal of this study is to determine the differences in the relationships that link physiological variables that characterize the elderly and men, and those that characterize fatal outcomes in young men. To accomplish this, we examined a database of patients with moderate to severe COVID-19 (471 men and 277 women) registered at the “Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán” in March 2020. The sample was stratified by outcome, age, and sex. Physiological networks were built using 67 physiological variables (vital signs, anthropometric, hematic, biochemical, and tomographic variables) recorded upon hospital admission. Individual variables and system behavior were examined by descriptive statistics, differences between groups, principal component analysis, and network analysis. We show how topological network properties, particularly clustering coefficient, become disrupted in disease. Finally, anthropometric, metabolic, inflammatory, and pulmonary cluster interaction characterize the deceased young male group.

Stratified Multivariate Multiscale Dispersion Entropy for Physiological Signal Analysis

“…It is important to note that when designating the RR channel, the largest mean absolute difference is observed for both T-SmvMDE and P-SmvMDE as well as the largest number of entries where the LS DisEn values are higher than the HS ones. This points towards a LoC process [10], [28] when moving from a steady state to a state that induces increased stress in the system, in alignment with the EP hypothesis [8], [29].…”

“…Additionally, the mean absolute difference observed in each difference distribution and the number of entries that displayed an increased absolute value of difference during each SmvMDE configuration, compared to their mvMDE values, are reported. Finally, to highlight a potential directionality that could match the EP hypothesis [8], [29], the number of entries with a higher entropy value in the LS state than in the HS state are also reported for each configuration.…”

“…These seemingly opposite paradigms are combined in the EP hypothesis that separates physiological parameters in regulated and effector variables. Based on this hypothesis, an "entropy pump" is observed, thanks to which homeostasis is achieved, by maintaining a stable, low complexity output for regulated variables through the complex and variable outputs of effector variables [8], [29]. A pathological state is observed when its direction is disrupted and an increase in the complexity of regulated variables is observed as per the CSD paradigm, while a decrease in the complexity of the effector variables is observed in accordance with the LoC paradigm.…”

Risk factors contributing to infection with SARS-CoV-2 are modulated by sex

“…Other studies have indicated that female COVID-19 patients have an increased risk to develop long COVID [ 43 – 45 ], whereas male patients have higher odds of requiring intensive treatment unit (ITU) admission or of having a fatal outcome [ 46 ]. Previously, we have explained the distinct evolution of COVID-19 for both sexes in terms of differences in the structure of their corresponding physiological networks [ 40 , 42 ].…”

Polymerised type I collagen modifies the physiological network of post‐acute sequelae of COVID‐19 depending on sex: a randomised clinical trial

“…3 Females generally exhibit a better prognosis than males for acute systemic diseases such as COVID-19, attributed to their more robust physiological networks. 4 However, little is known about the impact of PASC, lowgrade inflammation 5 and sex differences on this systemic structure.Polymerised type I collagen (PTIC) is a potential drug for treating COVID-19 patients, proven to be effective against rheumatoid arthritis, 6,7 and is being investigated in multiple preclinical studies for other diseases.We analysed the data from a double-blind, randomised controlled trial of PTIC, [6][7][8][9] as an immune down-regulator, in COVID-19. We examined the dynamics of the physiological network, which characterises system-wide modifications during post-acute recovery.Between August 31 and November 7, 2020, 89 unvaccinated adult outpatients with Polymerase Chain Reaction (PCR)-confirmed COVID-19 were treated at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.…”