Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota

Abstract

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (R_t) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the R_t of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19.

Fig. 1. Alpha and Iota dominated the circulating SARS-CoV-2 populations in Connecticut and New York City in early 2021.

a Trends in COVID-19 incidence were consistent across northeastern states throughout the pandemic. (map) Connecticut (teal) is bordered by New York, Rhode Island, and Massachusetts. New York City is less than 50 miles from Fairfield County. Weekly COVID-19 incidence was tabulated according to the Johns Hopkins COVID-19 portal (https://github.com/CSSEGISandData/COVID-19). Shapefile source: United States Census Bureau. b New Haven County led the state in the percentage of COVID-19 cases sequenced between November 30, 2020 and May 9, 2021 (3.33%). During this period, 0.51% of COVID-19 cases in New York City were sequenced. Genomes that were collected through targeted variant screening (e.g., spike-gene target failure) were excluded from this analysis. Shapefile source: the Connecticut Department of Energy & Environmental Protection (DEEP) Geographic Information Systems Open Data Website. c Together, Alpha and Iota variants displaced nearly all other SARS-CoV-2 lineages in New Haven County (n = 2086), Fairfield County (n = 612), and New York City (n = 4528). The lineages of sequenced viruses were assigned using pangolin v.2.4.2. The lineages B.1.526, B.1.526.1, and B.1.526.2 were assigned to the general lineage category ‘Iota’. We calculated a 7-day rolling average for the proportion of Alpha, Iota, and ‘other’ SARS-CoV-2 lineages sequenced in our dataset. d Daily variant incidence estimated by fitting a logistic growth model to the daily sequenced variant frequencies shown in c. This analysis was completed using Rv.4.0.1. Line colors correspond to the legend in c. e Daily growth rates of variants estimated using the logistic growth model shown in d. Bar colors correspond to the legend in c.

Fig. 2. Alpha and Iota had a larger effective reproduction number (R_t) than other circulating lineages in the first half of 2021.

a, d Daily incidence and full vaccination rates (2 weeks post last dose) of Alpha, Iota, and other circulating lineages in New Haven County (a) and New York City (d). Estimated daily infections were assigned to one of three lineage categories (‘Alpha’, ‘Iota’, and ‘other’) according to the 7-day rolling average of variant frequency among sequenced cases. ‘Iota’ includes the sublineages B.1.526, B.1.526.1, and B.1.526.2. b, e Time-varying effective reproduction numbers (R_t) were calculated using the R package EpiEstim. An R_t value above 1 indicates that an infected individual will, on average, infect more than 1 additional person. We assumed a serial interval of mean 5.2 days and standard deviation of 4 days for all lineages. 0.025 and 0.975 quantiles are shown as dotted lines. c, f Ratios of estimated R_t between January 24 and April 24, 2021. The mean and 95% CI for the scatter plots are shown in black.

Fig. 3. Alpha was introduced into Connecticut at a similar frequency as Iota but was associated with larger cluster sizes.

a, b Discrete phylogeography of Alpha (a) and Iota (b). Tips and nodes were assigned one of four possible locations: Connecticut, New York/New Jersey, domestic, and international. The phylogeographic analysis was performed in BEAST using a time-resolved tree as the fixed topology. Bootstrap values for each clade are shown at each ancestral node (right) and were obtained by constructing individual maximum likelihood trees with 1000 ultrafast bootstraps in IQTree. Clades without a support value were part of polytomies. c We summed the number of sustained introductions for each variant by week. We defined sustained introductions as Connecticut-only clades containing at least 3 tips related by a non-Connecticut ancestor with at least 0.7 posterior probability for the inferred location. Bar colors indicate the source of introduction. Error bars show the range of the five replicates per variant. d There were more sustained introductions of Iota than Alpha into Connecticut. The horiztonal bars show the median and 95% CI over five replicates per variant. e The size of Alpha clades in Connecticut was on average larger than Iota clades in Connecticut. We calculated the log₁₀ size of Connecticut clades shown in a, b. The horizontal lines denote the median and 95% CI log cluster size.