The Good, The Bad and The Ugly: A Mathematical Model Investigates the Differing Outcomes Among CoVID-19 Patients
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The Good, The Bad and The Ugly: A Mathematical Model Investigates the Differing Outcomes Among CoVID‑19 Patients Sarthak Sahoo, Siddharth Jhunjhunwala and Mohit Kumar Jolly* Abstract | The disease caused by SARS-CoV-2—CoVID-19—is a global pandemic that has brought severe changes worldwide. Approximately 80% of the infected patients are largely asymptomatic or have mild symptoms such as fever or cough, while rest of the patients display vary‑ ing degrees of severity of symptoms, with an average mortality rate of 3–4%. Severe symptoms such as pneumonia and acute respiratory dis‑ tress syndrome may be caused by tissue damage, which is mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm. Here, we discuss how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinicopathological outcomes. Particu‑ larly, we discuss how the emergent nonlinear dynamics of interaction among the components of adaptive and immune system components and virally infected cells can drive different disease severity. Such mini‑ malistic yet rigorous mathematical modeling approaches are helpful in explaining how various co-morbidity risk factors, such as age and obe‑ sity, can aggravate the severity of CoVID-19 in patients. Furthermore, such approaches can elucidate how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe phenotypes. These results can help further in a rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage. 1 Introduction The world has been severely impacted by the ongoing CoVID-19 pandemic on multiple perspectives: economic, social, and public health. Various candidates for vaccines are in different stages of development, and as we await to learn about the efficacy and longevity of these targeted outcomes, it becomes imperative to understand the underlying biology of the disease that can inform the rational design of treatment options for the people who have already contracted the virus. In this perspective, we aim to summarize in one part the biology of the SARS-CoV-2 infection, which relates to responses of adaptive and
J. Indian Inst. Sci. | VOL xxx:x | xxx–xxx 2020 | journal.iisc.ernet.in
innate arms of our immune system. In the second part, we discuss how mathematical modeling of the interactions between immune cells and virally infected cells can help inform rational design of treatment options. 2 What is SARS‑CoV‑2? Human coronaviruses, first identified in the 1960s1, commonly infect humans. Most coronavirus infections are respiratory in nature and primarily affect the upper respiratory tract and the lungs2. There are 7 identified coronaviruses that have been documented to infect humans—229E,
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Cytokine storm: A sudden acute increase in circulating levels of different inflammation cau
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