ABSTRACT
Background: Countries around the world have introduced travel restrictions to reduce SARS-CoV-2 transmission. As vaccines are gradually rolled out, attention has turned to when travel restrictions and other non-pharmaceutical interventions (NPIs) can be relaxed. Methods: Using SARS-CoV-2 as a case study, we develop a mathematical branching process model to assess the risk that, following the removal of NPIs, cases arriving in low prevalence settings initiate a local outbreak. Our model accounts for changes in background population immunity due to vaccination. We consider two locations with low prevalence in which the vaccine rollout has progressed quickly - specifically, the Isle of Man (a British crown dependency in the Irish Sea) and the country of Israel. Results: We show that the outbreak risk is unlikely to be eliminated completely when travel restrictions and other NPIs are removed. This general result is the most important finding of this study, rather than exact quantitative outbreak risk estimates in different locations. It holds even once vaccine programmes are completed. Key factors underlying this result are the potential for transmission even following vaccination, incomplete vaccine uptake, and the recent emergence of SARS-CoV-2 variants with increased transmissibility. Conclusions: Combined, the factors described above suggest that, when travel restrictions are relaxed, it may still be necessary to implement surveillance of incoming passengers to identify infected individuals quickly. This measure, as well as tracing and testing (and/or isolating) contacts of detected infected passengers, remains useful to suppress potential outbreaks while global case numbers are high.
ABSTRACT
While the pathological mechanisms in COVID-19 illness are still poorly understood, it is increasingly clear that high levels of pro-inflammatory mediators play a major role in clinical deterioration in patients with severe disease. Current evidence points to a hyperinflammatory state as the driver of respiratory compromise in severe COVID-19 disease, with a clinical trajectory resembling acute respiratory distress syndrome, but how this 'runaway train' inflammatory response emerges and is maintained is not known. Here, we present the first mathematical model of lung hyperinflammation due to SARS-CoV-2 infection. This model is based on a network of purported mechanistic and physiological pathways linking together five distinct biochemical species involved in the inflammatory response. Simulations of our model give rise to distinct qualitative classes of COVID-19 patients: (i) individuals who naturally clear the virus, (ii) asymptomatic carriers and (iii-v) individuals who develop a case of mild, moderate, or severe illness. These findings, supported by a comprehensive sensitivity analysis, point to potential therapeutic interventions to prevent the emergence of hyperinflammation. Specifically, we suggest that early intervention with a locally acting anti-inflammatory agent (such as inhaled corticosteroids) may effectively blockade the pathological hyperinflammatory reaction as it emerges.