Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

The strategy of relying solely on current SARS-CoV-2 vaccines to halt SARS-CoV-2 transmission has proven infeasible. In response, many public-health authorities have advocated for using vaccines to limit mortality while permitting unchecked SARS-CoV-2 spread (“learning to live with the disease”). The feasibility of this strategy critically depends on the infection fatality rate (IFR) of SARS-CoV-2. An expectation exists that the IFR will decrease due to selection against virulence. In this work, we perform a viral fitness estimation to examine the basis for this expectation. Our findings suggest large increases in virulence for SARS-CoV-2 would result in minimal loss of transmissibility, implying that the IFR may vary freely under neutral evolutionary drift. We use an SEIRS model framework to examine the effect of hypothetical changes in the IFR on steady-state death tolls under COVID-19 endemicity. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to unsustainable mortality burdens. Our findings highlight the importance of enacting a concerted strategy and continued development of biomedical interventions to suppress SARS-CoV-2 transmission and slow its evolution.https://www.mdpi.com/2673-8112/2/12/121Published versio

Endemicity Is Not a Victory: The Unmitigated Downside Risks of Widespread SARS-CoV-2 Transmission

The strategy of relying solely on current SARS-CoV-2 vaccines to halt SARS-CoV-2 transmission has proven infeasible. In response, many public-health authorities have advocated for using vaccines to limit mortality while permitting unchecked SARS-CoV-2 spread (“learning to live with the disease”). The feasibility of this strategy critically depends on the infection fatality rate (IFR) of SARS-CoV-2. An expectation exists that the IFR will decrease due to selection against virulence. In this work, we perform a viral fitness estimation to examine the basis for this expectation. Our findings suggest large increases in virulence for SARS-CoV-2 would result in minimal loss of transmissibility, implying that the IFR may vary freely under neutral evolutionary drift. We use an SEIRS model framework to examine the effect of hypothetical changes in the IFR on steady-state death tolls under COVID-19 endemicity. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to unsustainable mortality burdens. Our findings highlight the importance of enacting a concerted strategy and continued development of biomedical interventions to suppress SARS-CoV-2 transmission and slow its evolution

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.Multiple funders. See acknowledgments within article for details.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.semcancer.2015.09.00