The circulatory, musculoskeletal, immune, digestive, nervous, and other body systems are well known and taught in introductory biology. Each one serves a vital function in keeping the body alive, healthy, and safe. While we present them as separate entities that support our bodies, we often forget that they help each other and overlap significantly in some biological functions.

For example, the immune system protects us from invaders within our bodies, but the integumentary (skin) system serves as the first physical barrier against external threats. The digestive system also contributes to the immune system by releasing proteins called lysozymes into saliva. These proteins break down bacterial cell walls and membranes, effectively killing the germs we accidentally ingest. There are plenty of other relationships like this within the body, and research is finding more ways in which our body systems intertwine due to the effects of diseases.

COVID-19, the infamous pandemic that shut down the world in 2020, is one disease that has made researchers focus more on how our organ systems interact. While COVID-19 was recognized for its effects on the respiratory system, studies revealed that it also severely affected the renal (kidney), nervous, and cardiovascular systems.

With the disease impacting and disrupting the function of multiple organ systems at once, health care providers faced an issue of managing patients who had numerous organ issues during a single hospitalization. While epidemiological studies can identify disease risk factors, experimental studies can determine the mechanisms by which a pathogen causes the disease.

Unfortunately, it takes time for experimental studies to identify mechanisms, so medical professionals are exploring a new model, network physiology, to adapt treatments and resources during outbreaks.

Network physiology is a multidisciplinary field that combines microbiology, cell biology, physiology, anatomy, and other specialties to analyze the complex interactions within the human body. This robust field focuses on the connections between organs to monitor health, diagnose disease, and guide treatment. There are two major approaches to understanding this connectivity.

The first, the correlation network, suggests that disrupted organ networks are linked with poor outcomes in critically ill patients. The second, the parenclitic network, examines organ connections within a patient to predict disease outcomes and responses to therapies. To highlight the potential of this field in counteracting pandemics, researchers from University College London analyzed COVID-19 patient data using network physiology to determine how it would guide treatment decisions and improve patient outcomes.

Of the 202 hospitalized COVID-19 patients whose data were analyzed, 54 died (designated as non-survivors) while the remaining 148 were discharged. The 54 non-survivors shared characteristics such as older age, reduced oxygen in blood vessels, lower blood pressure, and reduced levels of consciousness.

The non-survivors also had elevated creatinine, blood urea nitrogen (BUN), and aspartate aminotransferase (AST) levels, which are clinical signs of dehydration and damage to the liver, heart, and muscles. By using physiological network analysis of the data, the researchers identified two clusters of organ connectivity in patients: a renal cluster and a liver enzyme cluster.

Among the renal cluster, non-survivors had higher BUN levels, which corresponded with higher potassium levels, suggesting kidney damage. On the other hand, survivors did not have this correlation. Instead, survivor potassium levels were correlated with healthy blood pH, as potassium can serve as an adaptive response to disrupted pH.

From this cluster, the researchers conclude that the potassium-pH relationship in survivors reflects physiological compensation during disease. In contrast, the BUN-potassium relationship in non-survivors reflects a life-threatening disruption. With this information, medical personnel could be warned against using medications or antivirals that are toxic to the kidneys during the initial stages of an outbreak.

In the liver enzyme cluster, AST levels were associated with reduced levels of consciousness in the non-survivors. The researchers state that this association may be due to the liver-brain connection or impairments in urea recycling, but further research is needed to confirm these hypotheses. However, this cluster is still valuable information, as the effects of COVID-19 on the liver are complex, and the levels of liver enzymes during infection have been a predictor for patient mortality.

Taken together, these findings demonstrate that focusing on networks of organ interactions can significantly improve our understanding, monitoring, and treatment of disease during fast-moving outbreaks. This study applied physiological network patterns to COVID-19 patient data to distinguish adaptive responses from dangerous system failures.

More importantly, this approach is not limited to COVID-19. Any emerging pathogen that triggers cascading effects across organ systems, such as influenza, Ebola, dengue, etc., could be better managed by mapping how disruptions spread through the body’s interconnected networks. By expanding focus from individual organ health to whole-body health, physiology networking can identify early warning signatures of organ stress, predict which patients are likely to develop critical symptoms, and highlight which treatments may worsen underlying vulnerabilities. As a tool, network physiology can strengthen outbreak preparedness across a wide range of diseases.

Reference

Ji CX, Sorouri M, Abdollahi M, Paknejad O, & Mani AR. (2025) Can physiological network mapping reveal pathophysiological insights into emerging diseases? Lessons from COVID-19. at Plos One 20(11): e0337333.