Quantifying the potential dominance of immune-evading SARS-CoV-2 variants in the United States

Sah, Pratha; Vilches, Thomas N.; Shoukat, Affan; Pandey, Abhishek; Fitzpatrick, Meagan C.; Moghadas, Seyed M.; Galvani, Alison P.

doi:10.1101/2021.05.10.21256996

Cited by 6 publications

(8 citation statements)

References 21 publications

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“…We expanded our age-stratified, agent-based model (ABM) of COVID-19 to simulate the spread of SARS-CoV-2 variants, including Alpha, Gamma, Delta, and Iota variants in addition to the original Wuhan-1 strain (Figure S1). 9 , 10 , 11 The basic structure of the ABM includes a finite collection of agents that represent individuals living in a population, and a virtual environment in which agents interact. 12 Agents are assigned specific attributes (e.g., age, comorbidities) and are characterized by time-dependent epidemiological statuses.…”

Section: Methodsmentioning

confidence: 99%

COVID-19 hospitalizations and deaths averted under an accelerated vaccination program in northeastern and southern regions of the USA

Vilches

Sah

Moghadas

et al. 2022

The Lancet Regional Health - Americas

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Background The fourth wave of COVID-19 pandemic peaked in the US at 160,000 daily cases, concentrated primarily in southern states. As the Delta variant has continued to spread, we evaluated the impact of accelerated vaccination on reducing hospitalization and deaths across northeastern and southern regions of the US census divisions. Methods We used an age-stratified agent-based model of COVID-19 to simulate outbreaks in all states within two U.S. regions. The model was calibrated using reported incidence in each state from October 1, 2020 to August 31, 2021, and parameterized with characteristics of the circulating SARS-CoV-2 variants and state-specific daily vaccination rate. We then projected the number of infections, hospitalizations, and deaths that would be averted between September 2021 and the end of March 2022 if the states increased their daily vaccination rate by 20 or 50% compared to maintaining the status quo pace observed during August 2021. Findings A 50% increase in daily vaccine doses administered to previously unvaccinated individuals is projected to prevent a total of 30,727 hospitalizations and 11,937 deaths in the two regions between September 2021 and the end of March 2022. Southern states were projected to have a higher weighted average number of hospitalizations averted (18.8) and lives saved (8.3) per 100,000 population, compared to the weighted average of hospitalizations (12.4) and deaths (2.7) averted in northeastern states. On a per capita basis, a 50% increase in daily vaccinations is expected to avert the most hospitalizations in Kentucky (56.7 hospitalizations per 100,000 averted with 95% CrI: 45.56 - 69.9) and prevent the most deaths in Mississippi, (22.1 deaths per 100,000 population prevented with 95% CrI: 18.0 - 26.9). Interpretation Accelerating progress to population-level immunity by raising the daily pace of vaccination would prevent substantial hospitalizations and deaths in the US, even in those states that have passed a Delta-driven peak in infections. Funding This study was supported by The Commonwealth Fund. SMM acknowledges the support from the Canadian Institutes of Health Research [OV4 – 170643, COVID-19 Rapid Research] and the Natural Sciences and Engineering Research Council of Canada, Emerging Infectious Disease Modelling, MfPH grant. MCF acknowledges support from the National Institutes of Health (5 K01 AI141576).

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Section: Methodsmentioning

confidence: 99%

COVID-19 hospitalizations and deaths averted under an accelerated vaccination program in northeastern and southern regions of the USA

Vilches

Sah

Moghadas

et al. 2022

The Lancet Regional Health - Americas

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“…During 2021, prior to the omicron wave, several studies have hypothesized different scenarios for the winter period 2021/2022. Sah et al [22] have built several models to predict the situation in the USA. These authors state that immune escape has to be coupled with increased transmission rates for a variant to be successful.…”

Section: Discussionmentioning

confidence: 99%

“…The authors of [23] show that immune escape can slowly develop future waves that might not be easily predictable and can hit the population at later stages of the pandemic. Compared to our study, [22, 23] make long term predictions while we focus on the short period of quick replacement by omicron of the delta variant which lasted, as outlined, only three weeks.…”

Section: Discussionmentioning

confidence: 99%

Retrospective analysis of SARS-CoV-2 omicron invasion over delta in French regions in 2021-22: a status-based multi-variant model

Haschka

Vergu

Roche

et al. 2022

Preprint

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Background: SARS-CoV-2 is a rapidly spreading disease affecting human life and the economy on a global scale. The disease has caused so far more then 5.5 million deaths. The omicron outbreak that emerged in Botswana in the south of Africa spread around the globe at further increased rates, and caused unprecedented SARS-CoV-2 infection incidences in several countries. At the start of December 2021 the first omicron cases were reported in France. Methods: In this paper we investigate the contagiousness of this novel variant relatively to the delta variant that was also in circulation in France at that time. Using a dynamic multi-variant model accounting for cross-immunity through a status-based approach, we analyze screening data reported by Sante Publique France over 13 metropolitan French regions between 1st of December 2021 and the 30th of January 2022. During the investigated period, the delta variant was replaced by omicron in all metropolitan regions in approximately three weeks. The analysis conducted retrospectively allows us to consider the whole replacement time window and compare regions with different times of omicron introduction and baseline levels of variants' transmission potential. As large uncertainties regarding cross-immunity among variants persist, uncertainty analyses were carried out to assess its impact on our estimations. Results: Assuming that 80% of the population was immunized against delta, a cross delta/omicron cross-immunity of 25% and omicron generation time was 3.5 days, the relative strength of omicron to delta, expressed as the ratio of their respective reproduction rates, R[omicron]/R[delta], was found to range between 1.51 and 1.86 across regions. Uncertainty analysis on epidemiological parameters led to R[omicron]/R[delta] ranging over 1.57-2.13 when averaged over the metropolitan French regions, weighting by population size. Conclusions: Upon introduction, omicron spread rapidly through the French territory and showed a high fitness relative to delta. We documented considerable geographical heterogeneities on the spreading dynamics. The historical reconstruction of variant emergence dynamics provide valuable ground knowledge to face future variant emergence events.

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“…3×10 5 Vero-TMPRSS2 cells/well were seeded into 12-well plates in 1 mL of maintenance media and incubated overnight at 37⁰C and 5% CO2. The following day, cell confluency was confirmed to be >95% by visualization under a light microscope.…”

Section: Plaque Formation Assay (Pfa)mentioning

confidence: 99%

Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants

Pitts

Perry

et al. 2022

Preprint

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Genetic variation of SARS-CoV-2 has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern or interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV, VEKLURY®) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein ELISA and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with EC50 values 0.31 to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50 values ranging from 0.15 to 2.3-fold of the observed EC50 values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.

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Quantifying the potential dominance of immune-evading SARS-CoV-2 variants in the United States

Cited by 6 publications

References 21 publications

COVID-19 hospitalizations and deaths averted under an accelerated vaccination program in northeastern and southern regions of the USA

COVID-19 hospitalizations and deaths averted under an accelerated vaccination program in northeastern and southern regions of the USA

Retrospective analysis of SARS-CoV-2 omicron invasion over delta in French regions in 2021-22: a status-based multi-variant model

Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants

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