Department of Surgery

Divergent COVID-19 Archetypes Predicted by Individualized Perturbations of a Core Immune Regulatory Network

Date

May 6, 2021 - 8:30am

Event Description

Presenter: Dr. Yoram Vodovotz 

The long-term research goals in the Vodovotz lab are to obtain high-dimensional, dynamic data on the etiology and progression of various inflammatory processes and diseases in samples derived from cells, animals, and people; to create computational models based on these data as well as on key principles of immunology; and to modulate the inflammatory response in an optimal spatial, temporal, and individual- / disease-specific manner. In the present study, the lab focused on mathematical modeling of the host immune response to SARS-CoV2 infection. COVID-19 presentations range from mild to moderate through severe disease but also manifest with persistent illness or viral recrudescence. They hypothesized that these diverse pathophysiological manifestations of SARS-CoV-2 infections represent disease archetypes that emerge from cellular dynamics of a core immune response network, dysregulated by age, comorbidities, and genetic factors. Their framework highlights the role of innate and adaptive immune activation instigated via cellular damage of virus-infected cells in the context of an attenuated type I interferon response. A parsimonious, mechanistic mathematical model generated four distinct patient archetypes, whose disease and temporal dynamics were reflected in clinical and biomarker data from a cohort of hospitalized COVID-19 patients after calibration for initial viral load. The model accounts for responses to corticosteroid therapy and predicts that vaccine-induced neutralizing antibodies and cellular memory will protect most COVID-19 archetypes. This generalizable framework leverages the lab's prior work on mathematical modeling of inflammation and immunity and could be used to analyze protective and pathogenic immune responses to diverse viral infections.

Background reading:

Location and Address

Zoom virtual meeting

Zoom meeting logon info has been emailed to Department of Surgery staff. For Pitt and UPMC staff outside the department who wish to access the lecture, please email surgerywebmaster@upmc.edu.