A systemic model for Covid-19 based on game theory and viral load

The virus causing Covid-19 disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), is highly infectious, and the initial dose could be related to the severity of the infection. A direct relationship between the Viral Dose (VL) and the course of the infection would be consistent with a series of clinical and epidemiological evidence, which testify on the one hand the spread of the virus on a (still uncertain but) potentially very large number of people, and on the other the development of an extremely variable spectrum of symptoms and courses, from asymptomatic patients to others with a very serious course of the infection. Some recent studies have deepened the way in which SARS-CoV-2 attacks and destroys T-cells, fundamental in the response of the specific immune system, in a similar way to thebehavior of HIV. Other research has analyzed, with in silico models, the affinity between the spike protein of SARS-CoV-2 and human ACE2, finding that the high affinity (through energy bonds) between the two is at the base of the high contagiousness of the new coronavirus. After all, T-cells also have ACE2, albeit to a lesser extent, and high bond affinity couldbe the basis of the weakening mechanism of the adaptive immune system. Some research showed that the number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in Covid-19 patients, especially among elderly patients (≥60 years of age) and in patients requiring Intensive Care Unit (ICU) care. Due to its characteristics, Covid-19 tends on the one hand to evade the innate immune system, on the other hand to deactivate the specific, or adaptive, immune system. On the avoidance modality of the former, typical also of the other coronaviruses, the dynamics for Covid-19 is less clear, but some studies have been published to describe the main mechanisms. The average length of iincubation times for Covid-19 are moreover a testament to this. The interaction between the two immune systems is also crucial. The first (innate immune system) is evaded and sometimes enters late, the second (specific immune system) is inhibited, enters too early and sometimes too weakly. Too early, not in absolute terms, but with respect to the action of the former, who has not finished his task due to the circumvention effect. It follows that the two systems interfere and that the relay between the two systems is not optimal: the first sees that the second is ineffective and triggers the inflammatory storm. Both the avoidance level of the former and the deactivation level of the latter may be functions of the Viral Dose (VD). A systemic model based on Game Theory is proposed to describe how the Viral Dose, together with the presence of other pathologies, determines the collapse of the adaptive immune response, and the consequent inflammatory storm due to the interference with the innate immune system, which reacts to the inefficiency of the adaptive one. The model proposes the analogy of firefighters, in the role of T-cells, that are called in an emergency to extinguish fire outbreaks in a forest, which represent the viral outbreaks in the body. The model is essentially based on the availability of T-cells to cope with the different outbreaks, imagining each T-cell as a firefighter with its hydrant. When the APC cell (or the infected cell too) tries to activate T-cells, it finds these in 3 states: Free, Deactivated, Busy. The way in which the T-cell is deactivated by the virus is described in recent researches, as already mentioned. A T-cell Busy is instead an indication of a second ongoing pathology that has required its use (the firefighters are already engaged in another emergency, or in more emergencies, if there are multiple pathologies). We know that the number of deaths from Covid-19 is strongly correlated to the co-presence of one or more pathologies in progress, with the majority of deaths occurring with 2 or more pathologies in progress. Many mathematical models available in the literature can be used to build different simulations of activated T-cell densities, and different system response times, depending on other pathologies present compared to an optimal response condition of the adaptive system. The mechanism based on the game of the fireman offers a possible model that explains the dependence of the depression window on the Viral Dose, and also takes into account the pathologies already present in the patient, which have a decisive influence in the course of the infection. In this model, the depression window phenomenon is therefore linked to the Viral Dose through the mechanism by which the virus always attacks the T-cell ACE2, triggering the fireman's game. All mentioned researches are listed at the end of this paper and recalled in the body of the document