Divergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model.
Divergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model.
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DOI：
10.3389/fimmu.2021.754127
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发表时间：
2021
影响因子：
7.3
通讯作者：
Vodovotz Y
中科院分区：
文献类型：
--
作者：
Day JD;Park S;Ranard BL;Singh H;Chow CC;Vodovotz Y
COVID-19 presentations range from mild to moderate through severe disease but also manifest with persistent illness or viral recrudescence. We hypothesized that the spectrum of COVID-19 disease manifestations was a consequence of SARS-CoV-2-mediated delay in the pathogen-associated molecular pattern (PAMP) response, including dampened type I interferon signaling, thereby shifting the balance of the immune response to be dominated by damage-associated molecular pattern (DAMP) signaling. To test the hypothesis, we constructed a parsimonious mechanistic mathematical model. After calibration of the model for initial viral load and then by varying a few key parameters, we show that the core model generates four distinct viral load, immune response and associated disease trajectories termed “patient archetypes”, whose temporal dynamics are reflected in clinical data from hospitalized COVID-19 patients. The model also accounts for responses to corticosteroid therapy and predicts that vaccine-induced neutralizing antibodies and cellular memory will be protective, including from severe COVID-19 disease. This generalizable modeling framework could be used to analyze protective and pathogenic immune responses to diverse viral infections.
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
Casanova JL
影响因子：
17.1
作者：
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通讯作者：
Vodovotz, Yoram
影响因子：
5.6
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Banerjee, Abhirup;Ray, Surajit;Mackenzie, Louise S.
通讯作者：
Mackenzie, Louise S.
影响因子：
158.5
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Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
DOI：
10.1126/science.abc6261
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
Pulendran B