Strategies to Minimize Heterogeneity and Optimize Clinical Trials in Acute Respiratory Distress Syndrome (ARDS): Insights from Mathematical Modeling

Subudhi, Sonu; Cc, Voutouri; Cc, Hardin; Mr, Nikmaneshi; Ab, Patel; Verma, Anand Mohan; Mj, Khandekar; Dutta, Souvik; Stylianopoulos, Triantafyllos; Rk, Jain; Ll, Munn

doi:10.2139/ssrn.3857639

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It depends upon a large number of parameters whose values are not explicitly known for the SARS-CoV-2 virus. Here, and in our previous research, we have performed a robust sensitivity analysis of all major parameters of the model and have shown that model predictions might change quantitatively, but our conclusions are not affected qualitatively (27,41). In our approach, parameters are altered according to mechanistic hypotheses on the interaction between model components and outcome, which allows for direct testing of a hypothesis but at the cost of oversimplification of patient diversity and comorbidities.…”

Section: Discussionmentioning

confidence: 87%

Mechanistic model for booster doses effectiveness in healthy, cancer and immunosuppressed patients infected with SARS-CoV-2

Voutouria

Hardin

Naranbhai

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, vaccines are based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity, validate it with available clinical data, and predict vaccine effectiveness for varied vaccine platforms in the setting of variants with ability to escape immunity, increased virulence, or enhanced transmissibility. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts at least one more booster dose is required for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model is useful for planning future vaccinations, and tailoring strategies to risk groups.

show abstract

Section: Discussionmentioning

confidence: 87%