A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.

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Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.

The emergence of SARS-CoV-2 variants with evidence of antibody escape highlight the importance of addressing whether the total CD4+ and CD8+ T cell recognition is also affected. Here, we compare SARS-CoV-2-specific CD4+ and CD8+ T cells against the B.1.1.7, B.1.351, P.1, and CAL.20C lineages in COVID-19 convalescents and in recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. The total reactivity against SARS-CoV-2 variants is similar in terms of magnitude and frequency of response, with decreases in the 10%-22% range observed in some assay/VOC combinations. A total of 7% and 3% of previously identified CD4+ and CD8+ T cell epitopes, respectively, are affected by mutations in the various VOCs. Thus, the SARS-CoV-2 variants analyzed here do not significantly disrupt the total SARS-CoV-2 T cell reactivity; however, the decreases observed highlight the importance for active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution.

/pdf/impact-of-sars-cov-2-variants-on-the-total-cd4-and-cd8-t-1zyp9ak15l.pdf

Impact of SARS-CoV-2 variants on the total CD4 + and CD8 + T cell reactivity in infected or vaccinated individuals.

https://escholarship.org/content/qt9532h9t0/qt9532h9t0.pdf?t=qubj5x

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant.

A novel SARS-CoV-2 variant, VOC 202012/01, emerged in southeast England in November 2020 and appears to be rapidly spreading towards fixation. We fitted a two-strain mathematical model of SARS-CoV-2 transmission to observed COVID-19 hospital admissions, hospital and ICU bed occupancy, and deaths; SARS-CoV-2 PCR prevalence and seroprevalence; and the relative frequency of VOC 202012/01 in the three most heavily affected NHS England regions (South East, East of England, and London). We estimate that VOC 202012/01 is 56% more transmissible (95% credible interval across three regions 50-74%) than preexisting variants of SARS-CoV-2. We were unable to find clear evidence that VOC 202012/01 results in greater or lesser severity of disease than preexisting variants. Nevertheless, the increase in transmissibility is likely to lead to a large increase in incidence, with COVID-19 hospitalisations and deaths projected to reach higher levels in 2021 than were observed in 2020, even if regional tiered restrictions implemented before 19 December are maintained. Our estimates suggest that control measures of a similar stringency to the national lockdown implemented in England in November 2020 are unlikely to reduce the effective reproduction number Rt to less than 1, unless primary schools, secondary schools, and universities are also closed. We project that large resurgences of the virus are likely to occur following easing of control measures. It may be necessary to greatly accelerate vaccine roll-out to have an appreciable impact in suppressing the resulting disease burden.

/pdf/estimated-transmissibility-and-severity-of-novel-sars-cov-2-4prw8d2m72.pdf

Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England

/pdf/sars-cov-2-variants-of-concern-in-the-united-states-31ny4y4ohx.pdf

SARS-CoV-2 Variants of Concern in the United States-Challenges and Opportunities.

https://escholarship.org/content/qt2rw0t09q/qt2rw0t09q.pdf?t=qt3hfq

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

Author(s): Washington, Nicole L; Gangavarapu, Karthik; Zeller, Mark; Bolze, Alexandre; Cirulli, Elizabeth T; Schiabor Barrett, Kelly M; Larsen, Brendan B; Anderson, Catelyn; White, Simon; Cassens, Tyler; Jacobs, Sharoni; Levan, Geraint; Nguyen, Jason; Ramirez, Jimmy M; Rivera-Garcia, Charlotte; Sandoval, Efren; Wang, Xueqing; Wong, David; Spencer, Emily; Robles-Sikisaka, Refugio; Kurzban, Ezra; Hughes, Laura D; Deng, Xianding; Wang, Candace; Servellita, Venice; Valentine, Holly; De Hoff, Peter; Seaver, Phoebe; Sathe, Shashank; Gietzen, Kimberly; Sickler, Brad; Antico, Jay; Hoon, Kelly; Liu, Jingtao; Harding, Aaron; Bakhtar, Omid; Basler, Tracy; Austin, Brett; Isaksson, Magnus; Febbo, Phil; Becker, David; Laurent, Marc; McDonald, Eric; Yeo, Gene W; Knight, Rob; Laurent, Louise C; de Feo, Eileen; Worobey, Michael; Chiu, Charles; Suchard, Marc A; Lu, James T; Lee, William; Andersen, Kristian G | Abstract: As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

/pdf/genomic-epidemiology-identifies-emergence-and-rapid-2jbkkptn4d.pdf

Geraint Levan

Papers

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States