The development of COVID-19 in the human body from the lens of the five-phase system
As an essential constituent of Chinese scientific holism, the notion of the five-phase system provides prominent insights for explaining the phases of COVID-19 development in humans infected by 2019-nCoV (as shown in Fig. 3). When 2019-nCoV invades a human, it causes symptoms such as fever and dry cough. These symptoms lead the infected person into a state of gradual change of his/her organs. Simultaneously, the 2019-nCoV attacks the infected person’s lungs and other organs directly, resulting in physical and functional damages when it reaches sufficient concentration. In response, the attacked organs instruct that the body activates the immune system to fight the coronavirus by mobilizing the immune cells to destroy the virus cells. The infected person with a strong immunity generates an appropriate level of immune reaction against 2019-nCoV. The development of the disease could be controlled by mobilizing the body’s immune cells (lymphocytes, white blood cells, neutrophils, etc.) against 2019-nCoV. TCM is broadly adopted in the treatment of COVID-19 because it improves and maintains the immune system. However, for those with defective immunity, they are likely to exert overactive immune responses, which causes other healthy cells to be accidentally injured. During the operation of the immune system, it is difficult for the body to accurately recognize the disguised virus cells, resulting in indiscriminate attacks on the cells and thus, causing a storm of immunity and inflammation, which dramatically worsens the physical condition of the infected body.
As an external intervention, TCM and other medical treatments in Western biomedicine that tend to share a common basis with the dynamic disease paradigm (Dong and Zhang 2001; Herfel et al. 2011) play a non-negligible role in the treatment of COVID-19 by not intending to directly cancel the surfacing symptoms of the disease from the beginning, but complying with fundamental rules of the human body and adopting conservative measures to allow the infected person to improve his/her immunity over time. Hence, the inclination of an anaphylactic reaction is weakened. During the process of treatment along a relatively-long course, the infected person with strong immunity may win the fight between the COVID-19 and his/her immune system. In other words, through the proper supplementary treatment compatible with the complex dynamics orientation, the infected person may get to recover.
Dynamics uncovered from triadic closure to quadrangular cycle
When someone is infected with 2019-nCoV, causation appears showing the 2019-nCoV causes symptoms such as fever and dry cough (2019-nCoV intensity→symptoms of disease). TCM holds that, in essence, the symptoms of body surface indicate the disorders of internal organs (symptoms of disease→organ changes). Fever and inflammation indicate that the infected body is trying to suppress the virus. These symptoms are beneficial to avoid the probable occurrence of anaphylaxis and allow the infected body to gain time to adjust, resulting in an internal adaptation needed.Footnote 2 Meanwhile, the 2019-nCoV damages the organs. Particularly when the attack of coronavirus is too severe, or if it dexterously disguises itself to make the immune organ tolerate it similar to “self-antigens,” the infected body will suffer from unexpected organ changes (2019-nCoV intensity > −− organ changes). When infected by the coronavirus, the immune organs would produce antibodies. However, when antibodies bind to antigens, the histamines released by the basophils and mast cells may lead to the occurrence of immediate hypersensitivity.
The triadic closure (as shown in Fig. 4) constituted by 2019-nCoV intensity, symptoms of the disease, and organ changes contain two positive links and one negative link, thus forming a triadic structure of PPN. The 2019-nCoV intensity, as the reactant, makes the organs lesioned to some degree through the conjunctive effect of direct negative influence and indirect positive influence via the mediation of symptoms of the disease. Since there are two arcs incoming to the resultant (organ changes), the PPN is an imbalanced triad of transitive closure, according to FSBH.
The immune system is the body’s intrinsic mechanism that defends against foreign pathogenic microorganisms, including bacteria, viruses, and tuberculosis. Upon the recognition of the invaded virus, the body activates its immune reaction to fight against the virus. But due to its “disguise,” it takes time for the body to judge the coronavirus as antigens of harm. Thus, the infected body spontaneously instructs the immune system to mobilize the cells in various immune organs to react (organ changes→immune reaction), leading several immune cells and free radicals to attack the virus for seemingly providing defense for the body. That is, the immune system generates immune reaction for constraining the 2019-nCoV (immune reaction > −− 2019-nCoV intensity). The intensity of 2019-nCoV is actually a force-countering process between 2019-nCoV as an external force that attacks the body and the immune system as an internal force that defends the body. The net outcome depends on the result of the contest between the two forces. If the immune reaction is proper and effective, the influence of coronavirus is minor. Or else, the infected body suffers.
For the infected person with strong immunity, the change of immune organs is in a mild course toward the gradual and eventual production of antibodies corresponding to the antigens. Thus, the directed negative link from the intensity of the 2019-nCoV to organ changes (2019-nCoV intensity > −− organ changes) is weakened when the body’s endogenous immunity attacks the virus. Thus, the triadic cycle constituted by 2019-nCoV intensity, organ changes, and immune reaction contains two negative and one positive links (organ changes→immune reaction > −− 2019-nCoV intensity > −− organ changes), i.e., NPN, which indicates the formation of a cyclic loop for attacking the attacker (Fig. 5). According to system dynamics, it is a cyclic structure characterized by an imbalance derived from the mechanism of reinforcing feedback-loop.
As an external intervention, TCM plays a vital role in the treatment of COVID-19 because it does not act immediately to eliminate the symptoms. It pays utmost attention to locating the factor that improves body immunity, which strengthens the power of the immune system in its fight against the coronavirus. TCM terms immunity as vital energy and holds that the body could control the development of disease and recover when this vital energy is sufficient. When the vital energy is deficient, the disease is likely to bring about pathological changes to organs (Dong and Zhang 2001). This means that the key to the defense and treatment of COVID-19 is the maintenance of vital energy.
According to the above analyses, a sequential positive interlink exists along the chain of 2019-nCoV intensity, symptoms of the disease, organ changes, and immune reaction. The chained interlink indicates the formation of a larger structure based upon the conjunction of four interactive elements. In the quadrangular cycle, observed when the two different triads are placed consecutively in an integrated diagram (as shown in Fig. 6a), the 2019-nCoV intensity, as the reactant, influences the infected body to some degree of change. The result is a change in the state of the body’s organs, which is completed by the mediator (symptoms of disease). The net outcome is the aggregated result of indirect enabling force and direct constraining force from the same reactant (2019-nCoV intensity). Due to the suppression of constraining force from the reactant, the resultant (organ changes) is generated slowly. Then the resultant, as a self-adaptive agent, generates its catalyst (immune reaction) to put constraints on the reactant, resulting in the decrease of constraining force received by the resultant. Thus, the generation process of resultant is accelerated. The quadrangular cycle constituted by reactant, mediator, resultant, catalyst contains three positive links and one negative link, thus forming a balancing feedback-loop of PPPN. This cycle is a balanced structure that promises the stable and orderly generation of the targeted resultant.
The infected persons with strong immunity would generate moderate immune reactions and exert constraining force on the intensity of the 2019-nCoV, and gradually return to health. However, infected persons with deficient immunity would generate overactive immune responses such as anaphylactic shock. This activates the next quadrangular cycle. After the first quadrangular cycle is complete, the catalyst (immune reaction) that has completed its role may transform itself into the reactant of the continuous process in the quadrangular cycle (as shown in Fig. 6b). Thus it activates the generation of the next resultant (2019-nCoV intensity). That is, the immune reaction of the infected person as a reactant affects the intensity of 2019-nCoV under change via the mediation of physical condition. A body with strong immunity can reasonably and orderly mobilize the body’s immune cells according to the infection degree of 2019-nCoV to destroy the coronavirus and help the infected body recover gradually. However, when the coronavirus infects people with low immunity, the immune cells are prone to attacking cells, especially healthy cells making immune cells fight the infected organs. This is found to be the root cause of anaphylaxis, which includes inflammation, swelling, redness, fever, tingling, itching, anaphylactic shock, and organ failure.
Anaphylaxis destroys the body’s normal and abnormal cells, making the infected person weaker. The poor state of physical condition, in turn, makes the 2019-nCoV more virulent (physical condition→2019-nCoV intensity), and the increasing degree of infection of coronavirus causes more symptoms of the disease (2019-nCoV intensity→symptoms of disease). Symptoms such as fever indicate that the body is suppressing the coronavirus, and consuming drugs in haste to eliminate the symptoms may make the immune reaction more acute and aggressive. However, allowing the fever to persist for a while but keeping it within an acceptable limit may help the infected person avoid the subsequent inflammation (symptoms of disease > −− immune reaction). Under the current medical condition that there is no effective anti-viral drug against 2019-nCoV, the infected person demands the body to produce a moderate immune response to fight with 2019-nCoV (immunity reaction > −− 2019-nCoV intensity). TCM, good at improving the immunity, could prevent the progression of the disease and protect the organs from complications, thus enhancing the chance of activating the body’s moderate immune response, helping the recovery of an infected person.
This paired process of cyclic closure brings out a state change of the prior reactant. The second quadrangular cycle, constituted by the immune reaction (reactant), physical condition (mediator), 2019-nCoV intensity (resultant), and symptoms of the disease (catalyst), is isomorphic to the first cycle.
Sequentially, with the closure of attacking the attacker (Chase 1980), the third quadrangular cycle is ready to be activated if the catalyst of the second quadrangular cycle (symptoms of disease) transforms its role into the succeeding reactant to generate the change of state of the forthcoming resultant (immunity reaction), indicating another iteration of the quadrangular cycle. Hence, with the procession of regenerating the reactant, there appears a series of phase transitions.
From quadrangular cycle to five-nodal cycle (pentagon)
Simply put, we represent the above five components (2019-nCoV intensity, symptoms of disease, organ changes, immune reaction, and physical condition) by ABCDE as the generic codes for the focal five-nodal network/system. Putting the first and second quadrangular cycles into integration, we observe a structure in the shape of a pentagon. For illustration, Component A (2019-nCoV intensity), the reactant in the first cycle, transforms into the resultant in the second quadrangular cycle. In the pentagon-shaped structure, shown in Fig. 7a, both the reactant and the resultant are A, differing in state. Here, At, and At + 1 indicate the changes of component A.
In the first quadrangular cycle from At to Dt, which is governed by the inherent balancing feedback mechanism, the resultant Ct is generated stably owing to the energy transference from At as reactant, and component Dt catalyzes the process. Similarly, in the successive quadrangular cycle from Dt to Bt + 1, governed by the balancing feedback mechanism, At + 1 is generated stably given the energy stored in component Dt that is (re-)used as a reactant, and component Bt + 1 serves as a catalyst in the second generation process of cyclic closure as shown in Fig. 7b. Following that is the third quadrangular cycle from Bt + 1 to Et + 1, and the like.
We thus infer that every component of the five-phase system firstly acts as a reactant to transfer the energy for reproducing its constrainee (targets of the current generation process). Then it gets a payoff as resultant in the succeeding cycle to absorb the energy transferred from the specific reactant. This acts as a catalyst in the prior cycle; then, the reactant at the moment will get repaid in the forthcoming cycle. While each of the five components within a five-phase system has transformed from reactant to resultant, the entire system will finish a complete cycle at the macroscopic level. And because each component taking the turn as resultant will achieve its state change under the mechanism of balancing feedback in each quadrangular cycle, the whole cyclic process of the five-phase system presents itself as a spiral that operates under the mechanism of self-reinforcing feedback.
Therefore, we conclude that the five-phase system constituted by five positive and five negative links is a sound simplex model to portray a spiraling process of substantive generation through five phases of energy transference. This dynamic process is characterized by circular causality; that is, the reactant (cause) of the current cycle turns into the resultant (effect) of the next cycle.
From the pentagon to five-phase system
After the completion of one quadrangular cycle, which implies that the process of generating a specific resultant is complete, the catalyst turns into a reactant in the next quadrangular cycle. This activates another quadrangular cycle to reproduce the resultant which was the previous reactant. If we express the first quadrangular cycle as ABCD, then the second quadrangular cycle could be expressed as DEAB. Iteratively, the subsequent quadrangular cycles could be expressed as BCDE, EABC, CDEA, ABCD (the resultant is shown in bold). From this series, we observe that the sixth and the first quadrangular cycles are isomorphic. This indicates that after five quadrangular cycles, the whole system achieves an overall development of five-phase transitions in one spiraling period. The resultant of each phase-transition in a sequence is C, A, D, B, E, then returns to C, which implies that the late-coming C replaces the previous one. Hence, the whole process is a type of spiraling development of the five-phase system.
Overlaying the first-round five quadrangular cycles, we could observe the statically-pictured structure of the “five-element system” (as shown in Fig. 3). Herein, we can see the inappropriateness for the sloppy displacement of a spiral with a seemingly repetitious cycle, as portrayed by the frequently adopted but misleading translation of wuxing into “five elements.” Factually, if we expand this compressed five-element model along the temporal dimension, we could get a dynamic trajectory of continual spiraling shown in Fig. 8. And every quadrangular cycle in the spiral is qualified as a balanced intermediate form of the five-phase system. It is a stable carrier supporting the orderly generation of various resultants.
Notably, while acting as a reactant in the first quadrangular cycle, component A gets its energy gradually consumed. However, in the second quadrangular cycle, the same component turns into a resultant, and thus gradually gains the supplement of formerly-consumed energy. A similar situation occurs with other components, such as D, B, E, and C. While the reactant of the previous cycle becomes the resultant of the current cycle, the energy consumption and replenishment of each component achieves dynamic balance.