By Karyn Esser (@kaesser), Andrew Liu, Marcelo Febo (@marcelofebo), and Leah Reznikov (@leahreznikov), University of Florida
“[COVID-19] can attack almost anything in the body with devastating consequences,” says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. “Its ferocity is breathtaking and humbling.”
“Taking a systems approach may be beneficial as we start thinking about therapies,” says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).
These two statements point to the importance of bringing physiologists to COVID-19 research to understand the disease pathologies and to help develop therapeutic strategies (1). For diagnosis, because of the different ways that COVID-19 can present, it does help to have an understanding of systems physiology to be aware of how changes in one tissue/organ can impact others. For treating, this is really important as physicians have to always weigh the cost and benefit of treating one symptom with the potential impact on other organ functions. Making sure to just manage blood pressure, blood oxygen levels, and pulmonary function while not overloading the kidneys or liver is one example.
Prevention will be most definitely achieved with a vaccine but the pandemic has also brought forward the concept of systemic resilience. This means the ability for all the systems within the body to mount a challenge to the viral infections across all impacted organs but maintain enough homeostatic capacity, or balance within the entire body, for survival. If some organs are diminished in function due to infection can the rest of the system support it? For example, it turns out that skeletal muscle can help both liver and kidney with a capacity to metabolize things like ammonia.
COVID-19 is known as a respiratory disease, but the presentation of critical health problems are not isolated to the lungs and pulmonary function. While this is and will continue to be an area of significant research, they noted clinical issues with lungs, heart and vasculature (blood vessels), brain (eyes and nose), kidneys, intestines and liver. And it clearly brings in contributions from the immune system and whether that works well or goes into overdrive and generates a cytokine storm is proposed, but not uniform across all patients.
In other words, it is not just a lung dysfunction and respiratory disease; rather, it affects a multitude of these bodily functions, ranging from immune and inflammatory functions to neuroendocrine and to cell metabolism. Thus, COVID-19 is an attack on systemic physiology, not just one cell or organ and not just at one level.
Physicians are realizing that although the lungs are ground zero, the virus’ reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.
However, there could also be between organs/tissue changes that trigger outcomes such as kidney failure and liver disease. So whether the pathological outcomes are a direct result of viral infection, secondary to a cytokine storm, or downstream of primary changes in the lungs, heart or CNS is still to be solved and require systems-level research approaches teaming with molecular and cell biological methods.
Then you also have individual variation, prior health history and the question of why the mortality rates are higher in patients with diabetes or hypertension.
Could systemic resilience – or the ability of the system to work together – be a clue? Arguably, the best defense system is our physiology. Maintaining systemic physiological homeostasis by doing the right thing (e.g. sufficient amount of sleep and at the right time, proper diet and nutrition, and physical activity) can make our physiology stronger and thus heighten our ability to fend off or fight off the virus and reduce the symptoms. In this context, physiology is equally important for treatment, rehabilitation and recovery in a long term.
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