Early Genomic, Epidemiological, and Clinical Description of the SARS-CoV-2 Omicron Variant in Mexico City

Abstract

Omicron is the most mutated SARS-CoV-2 variant-a factor that can affect transmissibility, disease severity, and immune evasiveness. Its genomic surveillance is important in cities with millions of inhabitants and an economic center, such as Mexico City. Results. From 16 November to 31 December 2021, we observed an increase of 88% in Omicron prevalence in Mexico City. We explored the R346K substitution, prevalent in 42% of Omicron variants, known to be associated with immune escape by monoclonal antibodies. In a phylogenetic analysis, we found several independent exchanges between Mexico and the world, and there was an event followed by local transmission that gave rise to most of the Omicron diversity in Mexico City. A haplotype analysis revealed that there was no association between haplotype and vaccination status. Among the 66% of patients who have been vaccinated, no reported comorbidities were associated with Omicron; the presence of odynophagia and the absence of dysgeusia were significant predictor symptoms for Omicron, and the RT-qPCR Ct values were lower for Omicron. Conclusions. Genomic surveillance is key to detecting the emergence and spread of SARS-CoV-2 variants in a timely manner, even weeks before the onset of an infection wave, and can inform public health decisions and detect the spread of any mutation that may affect therapeutic efficacy.

Keywords: Omicron variant; R346K; SARS-CoV-2; dysgeusia; haplotype analysis; odynophagia; phylogenetic analysis.

Figure 1

The best-scoring ML phylogeny of Omicron SARS-CoV-2 samples collected in Mexico together with their closest worldwide relatives. (A) The best-scoring ML phylogeny of all sequences is presented. Black arrows indicate exchange events between the USA and Mexico. The gray arrow displays a group of sequences collected in Mexico that have largely diverged from the rest of the sequences. (B) A zoom on the region indicated by the blue line. (C) A zoom on the region indicated by the green line. Colors represent countries in which the analyzed sequences were collected. (D) Blue represents sequences collected in Mexico City; orange represents sequences collected in Mexico but not in Mexico City.

Figure 2

(A) Prevalence of the Omicron variant in Mexico City from 16 November to 31 December 2021 (week 45 to week 52). (B) Percentage of Omicron variant cases and symptom onset dates. (C) Correlation plot between the weekly growth rate of the epidemic curve and the proportion of Omicron variants in 4296 samples from SINAVE.

Figure 3

(A) Genome map of the SARS-CoV-2 Omicron variant with the most representative amino acid substitutions in 783 Omicron genomes in Mexico City with genome coverage >95%. Whole-genome SARS-CoV-2. (B) Spike protein with receptor-binding domain. The y-axis corresponds to the entropy calculated by the Nextclade tool.

Figure 4

Hierarchical clustering of the prevalence of amino acid substitutions in the spike protein among different countries in samples collected from 16 November to 31 December 2021, obtained from GISAID. We use one minus the Pearson correlation and clustering by region and the average as the linkage method. The scale represents the prevalence by each substitution in countries. Each cell contains the prevalence of the substitution as a percentage.

Figure 5

Haplotype network for all Omicron SARS-CoV-2 sequences from Mexico City. The size of each node is proportional to the number of samples that belong to that haplotype. The color represents the fraction of patient samples that were fully vaccinated for each haplotype. The white nodes belong to haplotypes with 100% nonvaccinated patients, and dark purple nodes belong to haplotypes with 100% fully vaccinated patients. The width of the lines is proportional to the number of mutations between two haplotypes.

Figure 6

Variable tree with the spread of samples based on variant of concern (VOC), sex, vaccination status, and hospitalization status. Not shown: a single sample in the Delta->male->not vaccinated->hospitalized branch that was the only sequenced case from a patient who died in the analysis period. Only 350 of the 783 samples sequenced were able to provide the clinical data for this analysis.

Figure 7

Daily fraction of all COVID-19-positive patients detected in Mexico City who reported dysgeusia as a symptom (by symptom onset date). Line color indicates the (weekly) percentage of sequenced samples identified as Omicron detected by genomic surveillance.

Figure 8

Ct distributions for each gene (nucleocapside, orf1ab, and Spike) used during the RT-qPCR test for Delta and Omicron SARS-CoV-2 samples. A two-sample t-test was performed for each marker. The corresponding p-value is shown in each case. The dashed lines represent the mean for each distribution.