Change Log

0.1.5

Mph passport was downloaded from IRT and upgraded to take into account lung specific features and implement new regulations
The upgraded Mph sub-model describes: (i) influx of monocytes (PBM) from bone marrow regulated by GMCSF, (ii) PBM migration to lung tissue stimulated by CCL2, CXCL10 and TGFb, (iii) PBM polarization to M1/M2 macrophages regulated by Antigen, IFNg, IL10, TGFb, IL4 and IL13, (iv) IL1b, IL6, IL10, IL12, IL23, TNFa, TGFb, CXCL10 and CCL2 production by the PBM and macrophages, (v) cytokine/chemokine distribution between lung tissue, plasma and lymph node, (vi) cytokine chemokine degradation
In vivo baseline data on PBM, iMph, M1, M2 and several cytokines/chemokines were extracted from Cytocon DB and further used for fitting of model parameters
Model is preliminary calibrated against available in vitro data describing regulatory effects of cytokines/chemokines on cell dynamics and then finally calibrated against in vivo baseline data measured for healthy subjects

To introduce new variable COVass_vpc designating assembled virus amount in vPC and implement release of COV from vPC from the variable. Delete release of the virus from COV_vpc.
Cell death leads to release of the virus bound with ACE2 at the cell surface. ACE2 is degraded.
To introduce 2 modes of immune response in empiric way: (i) Spike specific antibodies ( IgG/IgM) interfere binding of virus ACE2 (ii) stimulation of death of infected cells
Introduction of sputum dilution coefficient
Change in parameters k_rep_cov_rna_vpc , k_ass_cov_vpc , kbase_tran_pc_ipc , kbase_tran_ipc_vpc to describe clinically measured data on viral load and percent of subgenomic viral mRNA in sputum

To introduce limitation in number of virions able to bind to PCII cell to avoid non-physiological accumulation of (i) the virions on the cell surface and (ii) virus RNA in nucleus
Reproduction of clinical data on virus load dynamics

To develop a structure and to perform initial calibration of viral dynamics model for SARS-CoV-2