Divergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model.
Front Immunol
; 12: 754127, 2021.
Artigo
em Inglês
| MEDLINE | ID: covidwho-1518487
ABSTRACT
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.
Palavras-chave
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Alarminas
/
SARS-CoV-2
/
COVID-19
/
Tratamento Farmacológico da COVID-19
/
Modelos Biológicos
Tipo de estudo:
Estudo diagnóstico
/
Estudo prognóstico
Tópicos:
Covid persistente
/
Vacinas
Limite:
Adulto
/
Idoso
/
Humanos
/
Meia-Idade
Idioma:
Inglês
Revista:
Front Immunol
Ano de publicação:
2021
Tipo de documento:
Artigo
País de afiliação:
Fimmu.2021.754127
Similares
MEDLINE
...
LILACS
LIS