Understanding Neutrophil Dynamics during COVID-19 Infection
Source abstract
Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in varied clinical outcomes, with virus-induced chronic inflammation and tissue injury being associated with enhanced disease pathogenesis. To determine the role of tissue damage on immune populations recruitment and function, a mathematical model of innate immunity following SARS-CoV-2 infection has been proposed. The model was fitted to published longitudinal immune marker data from patients with mild and severe COVID-19 disease and key parameters were estimated for each clinical outcome. Analytical, bifurcation, and numerical investigations were conducted to determine the effect of parameters and initial conditions on long-term dynamics. The results were used to suggest changes needed to achieve immune resolution.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: COVID-19 Clinical Research Studies · Sepsis Diagnosis and Treatment · Long-Term Effects of COVID-19
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Mathematics, Virginia Polytechnic Institute and State University, 225 Stanger Street, Blacksburg, VA 24060, USA
Funding
National Science Foundation
References (84)
Show source-provided references
1. The pathogenesis of coronavirus-19 disease10.1186/s12929-022-00872-5 ↗
2. Cytokine storm in COVID-19: Pathogenesis and overview of anti-inflammatory agents used in treatment10.1007/s10067-020-05190-5 ↗
3. Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-1910.1084/jem.20210582 ↗
4. Distinct cytokine profiles associated with COVID-19 severity and mortality10.1016/j.jaci.2021.03.047 ↗
5. COVID-19 infection: An overview on cytokine storm and related interventions10.1186/s12985-022-01814-1 ↗
6. The cytokine storm and COVID-1910.1002/jmv.26232 ↗
7. De Kleijn, S., Langereis, J.D., Leentjens, J., Kox, M., Netea, M.G., Koenderman, L., Ferwerda, G., Pickkers, P., and Hermans, P.W. (2013). IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. PLoS ONE, 8.10.1371/journal.pone.0072249 ↗
8. Acute respiratory distress syndrome neutrophils have a distinct phenotype and are resistant to phosphoinositide 3-kinase inhibition10.1164/rccm.201509-1818OC ↗
9. Nonresolving inflammation10.1016/j.cell.2010.02.029 ↗
10. Review of mathematical modeling of the inflammatory response in lung infections and injuries10.3389/fams.2020.00036 ↗
11. Chronic inflammation: A failure of resolution?10.1111/j.1365-2613.2006.00507.x ↗
12. Neutrophils in COVID-1910.3389/fimmu.2021.652470 ↗
13. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients10.1016/j.ebiom.2020.102763 ↗
14. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China10.1001/jama.2020.1585 ↗
15. The inflammatory factors associated with disease severity to predict COVID-19 progression10.4049/jimmunol.2001327 ↗
16. Continuous tracking of COVID-19 patients’ immune status10.1016/j.intimp.2020.107034 ↗
17. Zhang, H., Wang, X., Fu, Z., Luo, M., Zhang, Z., Zhang, K., He, Y., Wan, D., Zhang, L., and Wang, J. (2020). Potential factors for prediction of disease severity of COVID-19 patients. medRxiv.10.1101/2020.03.20.20039818 ↗
18. A glimpse into the eye of the COVID-19 cytokine storm10.1016/j.ebiom.2020.102789 ↗
19. A mathematical model of neuroinflammation in severe clinical traumatic brain injury10.1186/s12974-018-1384-1 ↗
20. A quantitative model of thermal injury-induced acute inflammation10.1016/j.mbs.2010.08.003 ↗
21. Mathematical modeling of ventilator-induced lung inflammation10.1016/j.jtbi.2021.110738 ↗
22. A mathematical model for the immunotherapeutic control of the Th1/Th2 imbalance in melanoma
23. Andersen, M., Sajid, Z., Pedersen, R.K., Gudmand-Hoeyer, J., Ellervik, C., Skov, V., Kjær, L., Pallisgaard, N., Kruse, T.A., and Thomassen, M. (2017). Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development. PLoS ONE, 12.10.1371/journal.pone.0183620 ↗
24. Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis10.1093/imammb/dqs026 ↗
25. Rheumatoid arthritis-a mathematical model10.1016/j.jtbi.2018.10.039 ↗
26. Mathematical modelling of atherosclerosis as an inflammatory disease
27. Bistability analyses of CD4+ T follicular helper and regulatory cells during Helicobacter pylori infection10.1016/j.jtbi.2016.02.036 ↗
28. Modeling dynamic fluctuations in type 1 diabetes progression: Quantifying β-cell variation after the appearance of islet-specific autoimmune responses10.3934/mbe.2009.6.753 ↗
29. A mathematical model of the inflammatory response to pathogen challenge10.1007/s11538-018-0459-6 ↗
30. The resolution of inflammation: A mathematical model of neutrophil and macrophage interactions10.1007/s11538-014-9987-x ↗
31. Bistable Mathematical Model of Neutrophil Migratory Patterns After LPS-Induced Epigenetic Reprogramming10.3389/fgene.2021.633963 ↗
32. A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation10.1016/j.jtbi.2006.02.016 ↗
33. Clermont, G., Chow, C.C., Constantine, G.M., Vodovotz, Y., and Bartels, J. (2004). Classification, Clustering, and Data Mining Applications, Springer.
34. Global sensitivity analysis of a mathematical model of acute inflammation identifies nonlinear dependence of cumulative tissue damage on host interleukin-6 responses10.1016/j.jtbi.2014.05.036 ↗
35. Modeling the bistable dynamics of the innate immune system10.1007/s11538-018-0527-y ↗
36. Beauchemin, C.A., and Handel, A. (2011). A review of mathematical models of influenza A infections within a host or cell culture: Lessons learned and challenges ahead. BMC Public Health, 11.10.1186/1471-2458-11-S1-S7 ↗
37. Influenza and the challenge for immunology10.1038/ni1343 ↗
38. Cell-mediated protection in influenza infection10.3201/eid1201.051237 ↗
39. Pathogenesis of emerging avian influenza viruses in mammals and the host innate immune response10.1111/j.1600-065X.2008.00690.x ↗
40. Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus10.1128/JVI.00266-10 ↗
41. Ciupe, S.M., Ribeiro, R.M., and Perelson, A.S. (2014). Antibody responses during hepatitis B viral infection. PLoS Comput. Biol., 10.10.1371/journal.pcbi.1003730 ↗
42. Early events in hepatitis B infection: The role of inoculum dose10.1098/rspb.2020.2715 ↗
43. Ciupe, S.M., and Hews, S. (2012). Mathematical models of e-antigen mediated immune tolerance and activation following prenatal HBV infection. PLoS ONE, 7.10.1371/journal.pone.0039591 ↗
44. The role of cells refractory to productive infection in acute hepatitis B viral dynamics10.1073/pnas.0603626104 ↗
45. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury10.1128/mBio.00271-13 ↗
46. Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histo-blood group antibodies10.1093/glycob/cwn093 ↗
47. Jenner, A.L., Aogo, R.A., Alfonso, S., Crowe, V., Smith, A.P., Morel, P.A., Davis, C.L., Smith, A.M., and Craig, M. (2021). COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes. PLoS Pathog., 17.10.1101/2021.01.05.425420 ↗
48. Mathematical modeling of interaction between innate and adaptive immune responses in COVID-19 and implications for viral pathogenesis10.1002/jmv.25866 ↗
49. In-host mathematical modelling of COVID-19 in humans10.1016/j.arcontrol.2020.09.006 ↗
50. Chimal-Eguia, J.C. (2021). Mathematical model of antiviral immune response against the COVID-19 virus. Mathematics, 9.10.3390/math9121356 ↗
51. The good, the bad and the ugly: A mathematical model investigates the differing outcomes among COVID-19 patients10.1007/s41745-020-00205-1 ↗
52. Within host dynamics of SARS-CoV-2 in humans: Modeling immune responses and antiviral treatments10.1007/s42979-021-00919-8 ↗
53. Heitzman-Breen, N., and Ciupe, S.M. (2022). Modeling within-host and aerosol dynamics of SARS-CoV-2: The relationship with infectiousness. PLoS Comput. Biol., 18.10.1101/2022.03.08.483569 ↗
54. In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness10.1073/pnas.2111477118 ↗
55. Identifiability of parameters in mathematical models of SARS-CoV-2 infections in humans10.1038/s41598-022-18683-x ↗
56. A Multiscale Model of COVID-19 Dynamics10.1007/s11538-022-01058-8 ↗
57. Novel insights into immune and inflammatory responses to respiratory viruses10.1136/thoraxjnl-2012-202291 ↗
58. Resolution of inflammation: What controls its onset?10.3389/fimmu.2016.00160 ↗
59. Wound repair and regeneration: Mechanisms, signaling, and translation10.1126/scitranslmed.3009337 ↗
60. Resolution of inflammation: The beginning programs the end10.1038/ni1276 ↗
61. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury10.1007/s11427-020-1643-8 ↗
62. Dampening inflammation10.1038/ni1205-1179 ↗
63. The origin of alveolar macrophages in mouse radiation chimeras10.1084/jem.136.3.630 ↗
64. The survival and turnover of mature and immature CD8 T cells
65. Immunological memory and protective immunity: Understanding their relation10.1126/science.272.5258.54 ↗
66. Modeling the mechanisms of acute hepatitis B virus infection10.1016/j.jtbi.2007.02.017 ↗
67. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease10.1053/gast.2000.20229 ↗
68. Stability of cytokines, chemokines and soluble activation markers in unprocessed blood stored under different conditions10.1016/j.cyto.2016.05.010 ↗
69. Elimination half-lives of interleukin-6 and cytokine-induced neutrophil chemoattractant-1 synthesized in response to inflammatory stimulation in rats10.5625/lar.2018.34.2.80 ↗
70. Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers10.1016/S0009-9236(97)90065-5 ↗
71. Adaptive immunity to SARS-CoV-2 and COVID-1910.1016/j.cell.2021.01.007 ↗
72. An inflammatory cytokine signature predicts COVID-19 severity and survival10.1038/s41591-020-1051-9 ↗
73. Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-1910.1084/jem.20201012 ↗
74. Neutrophils in COVID-19: Not Innocent Bystanders10.3389/fimmu.2022.864387 ↗
75. COVID-19 and Preexisting Comorbidities: Risks, Synergies, and Clinical Outcomes10.3389/fimmu.2022.890517 ↗
76. CXCR2 antagonist MK-7123. A phase 2 proof-of-concept trial for chronic obstructive pulmonary disease10.1164/rccm.201405-0992OC ↗
77. Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis10.1016/j.rmed.2012.12.009 ↗
78. Dysregulation of interleukin-10–dependent gene expression in rheumatoid arthritis synovial macrophages10.1002/art.22055 ↗
79. Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis10.1084/jem.20021820 ↗
80. Xue, T.C., Zhang, L., Xie, X.Y., Ge, N.L., Li, L.X., Zhang, B.H., Ye, S.L., and Ren, Z.G. (2014). Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: A meta-analysis. PLoS ONE, 9.10.1371/journal.pone.0096072 ↗
81. Tumour-associated CD66b+ neutrophil count is an independent prognostic factor for recurrence in localised cervical cancer10.1038/bjc.2013.167 ↗
82. Hufford, M.M., Richardson, G., Zhou, H., Manicassamy, B., García-Sastre, A., Enelow, R.I., and Braciale, T.J. (2012). Influenza-infected neutrophils within the infected lungs act as antigen presenting cells for anti-viral CD8+ T cells. PLoS ONE, 7.10.1371/journal.pone.0046581 ↗
83. The prolonged life-span of alveolar macrophages10.1165/rcmb.2007-0224RC ↗
84. Ufimtseva, E., Eremeeva, N., Petrunina, E., Umpeleva, T., Karskanova, S., Bayborodin, S., Vakhrusheva, D., Kravchenko, M., and Skornyakov, S. (2018). Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis. PLoS ONE, 13.10.1371/journal.pone.0191918 ↗