The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City

Abstract

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We reported the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. We reported the effective reproduction number (Rt) of B.1.1.519 and presented evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519. The B.1.1.519 variant was predominant between November 2020 and May 2021, reaching 90% of all cases sequenced in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. Its Rt varies between 0.5 and 2.9. Its geographical origin remain to be investigated. Patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (p = 0.000296, 1.33-2.6 95% CI) and a 2.35-fold increase for hospitalization (p = 0.005, 1.32-4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves.

Keywords: B.1.1.519 variant; COVID-19 critical outcome; COVID-19 hospitalization; SARS-CoV-2; clinical impact; effective reproduction number; haplotype analysis; phylogenetic analysis; significant adjusted odds ratio.

Figure 1

(A) Frequencies of the B.1.1.519 variant in Mexico City from May 2020 to May 2021. (B) The geographic distribution of B.1.1.519 and B.1.1.222 variants in Mexico City, with dominance of the first variant. (C) Phylogenetic tree of SARS-CoV-2 with NextClade clades. The branch indicated with a red arrow represents 1879 sequences of the B.1.1.519 variant of Mexico City with coverage of >99.5%. (D) Genome map of SARS-CoV-2 variant B.1.1.519 with the most representative amino acid substitutions in 1879 sequences of the B.1.1.519 variant of Mexico City with coverage of >99.5%.

Figure 2

(A) Estimated number of cases for each variant based on the frequency observed in sequenced samples at INMG and the daily tally of confirmed cases in SINAVE, 7-day rolling average. (B) Time series of estimated Rt. Points represent the mean estimated Rt value per variant. Ribbon boundaries indicate the 5 (lower) and 95 (upper) quantile boundaries of the estimation.

Figure 3

Phylogenetic relationships of SARS-CoV-2 B.1.1.222 and B.1.1.519 lineages. A maximum likelihood phylodynamic inference was done of 84 SARS-CoV-2 sequences from Mexico in a global background of 19312 sequences available in the GISAID EpiCoV database as of 1 May 2020. Leaves are colored according to their Pango lineage: B.1.1.519 (red) and B.1.1.222 (blue) and according to their geographical origin: Mexico (green) and USA (gray). The bootstrap value of the mixed cluster (described in the main text) is shown.

Figure 4

Haplotype network of B.1.1.519 sequences. Node colors represent the month of appearance (pink- fuchsia: November or December, yellow: January, February or March; green: April or May). Node size is proportional to the number of samples for that specific haplotype, and border width is proportional to the prevalence of the haplotype. Numbers correspond to the number of samples for that specific haplotype. The blue-bordered node indicates the haplotype with the most ancient appearance date for lineage B.1.1.519.

Figure 5

Severity of illness across patient age groups and by presence of B.1.1.519 or non-B.1.1.519 SARS-CoV-2 infections. The figure shows absolute counts (upper) and proportions of patients (lower).