Abstract
Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses gives that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells can lead to more significant inflammation, proposing an explanation for the monotonic increase of COVID-19 mortality with age and higher mortality for males. We propose that T cells play a crucial role in the immunity against COVID-19, which provides a new direction–improvement of T cell number for advancing current prevention and treatment.
Highlights
Identifying key factors determining the immune heterogeneity from non-survivors to survivors is crucial for the current fight against the COVID-19 pandemic
Effector T cell and antibody dynamics are simulated to compare with real-time data from 10 individuals [35,36] and median values of mild and severe groups, survivors and nonsurvivors [3,45,46]
Zhang et al [4] deduced that the reduction of CD3+ T cells in serum represents the number of T cells that entered organs and produced effector T cells
Summary
Identifying key factors determining the immune heterogeneity from non-survivors to survivors is crucial for the current fight against the COVID-19 pandemic. Known as the cytokine storm which is thought likely to be a major cause of multiorgan failure [5,8]. For immune responses, both SARS-CoV-2 specific T cells and antibodies are observed in COVID-19 patients [7,9]. The quantitative role of these factors in antiviral and anti-inflammatory immune responses is unknown, resulting in several unsolved questions about the cause of death and the protective mechanism against virus and inflammation: 1. Are there new directions to overcome the heterogeneity of patients, decay of antibody function, and gene mutation SARS-CoV-2 in efficient therapeutics and vaccine developments?
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