It has been well established that most severe cases of COVID-19 are complicated by large viral loads and cytokine storms / inflammation. In an effort to improve therapies for COVID-19 hospitalized patients, therapeutic drugs have received unprecedented attention in the attempt to combat the viral infection and reduce inflammation. In this article, the impact of physical inactivity during a hospital stay is examined as a possible significant contributor to the development of severe and terminal cases. It is proposed that physical therapy and/or exercise for patients that may tolerate it would beneficially improve lymph flows which have been shown to have many positive effects on the immune system which can help to minimize progression of disease.
It is known that “Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Virus and host intrinsic characteristics strongly modulate the outcome of viral infections. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti‐viral immune activation and, counterintuitively, accelerates virus control.”
“Replication of virus in secondary lymphatic organs accelerates immune activation, and thereby helps to control the virus.”
“To infect its host, a virus must first enter cells at a body surface. Common sites of entry include the mucosal linings of the respiratory, alimentary, and urogenital tracts, the outer surface of the eye (conjunctival membranes or cornea), and the skin”
“Hematogenous spread begins when newly replicated particles produced at the entry site are released into the extracellular fluids, which can be taken up by the local lymphatic vascular system (Fig. 7). Lymphatic capillaries are considerably more permeable than circulatory system capillaries, facilitating virus entry. As the lymphatic vessels ultimately join with the venous system, virus particles in lymph have free access to the bloodstream. In the lymphatic system, virions pass through lymph nodes, where they encounter migratory cells of the immune system.”. The leukocytes and structures within the lymph system have the opportunity to inactivate and phagocytize the virus prior to the viral containing lymph fluids being returned to the venous system.
This means that immune response can be accelerated and improved simply by improving lymph flow. Since the adaptive and innate complement immune system cannot mount a significant response until the virus from a primary infection (first time) encounters the lymphatic or blood circulatory system, the immune system response is delayed and muted until significant amounts of virus enter that lymphatic system when some viruses bud out of an infected cell into the interstitial / lymph system. Once the adaptive immune system has had time to form various antibody isotypes such as IgM, IgA, and IgM, the venous system and mucousal areas have ample supply of immunoglobulins and complement innate leukocytes to also inactivate and phagocytize the virus.
“It has been known at least since the 1930s that lymph flow can be greatly augmented by passive limb motion.”
“Large lymph vessels contain an intrinsic pump in the form of lymphangions, which are under autonomic control (both sympathetic and parasympathetic) and produce a peristaltic wave.1 A larger-amplitude mechanical pumping is induced by muscle pumps, intrinsic visceral motion, and the rhythmic nature of respiration.”
“Lymphatic pump techniques have also been shown to mobilize leukocytes from gut-associated lymphoid tissue, significantly increase leukocyte count, and mobilize inflammatory mediators such as interleukin 8, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, granulocyte colony-stimulating factor, keratinocyte-derived chemoattractant, nitrite, and superoxide dismutase.”
Extrinsic lymphatic pumping through physical therapy and/or exercise may be particularly important with high BMI patients. “In humans, massive localized lymphoedema appears to be largely predicated on body mass index, although obese patients probably also fall under the spectrum of the metabolic syndrome, an amalgamation of metabolic impairments that are largely driven by obesity”.
Optimizing a patient’s immune response through physical therapy and/or exercise for patients that may tolerate it may be an important but missing element of COVID-19 therapy. Instead, many patients have been sedated and intubated or otherwise left to rest without helpful movement, laying virtually motionless in a hospital bed, with correspondingly low lymph flow. Improving lymph flow is an important part of improving immune response.
References
Please read this for more details regarding viral entry.
Also read this for more details on the importance of lymphatic system flow and immune response.
Also see:
Infection And Immune Response Lifecycle Overview
Staying Healthy with Exercise
Movement Matters – Pumping the Lymphatic System
