Genomic characterization of SARS-CoV-2 and its association with clinical outcomes: a 1-year longitudinal study of the pandemic in Colombia

Abstract

Objectives: This study aimed to explore associations between the molecular characterization of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and disease severity in ambulatory and hospitalized patients in two main Colombian epicentres during the first year of the coronavirus disease 2019 pandemic.

Methods: In total, 1000 patients with SARS-CoV-2 infection were included in this study. Clinical data were collected from 997 patients, and 678 whole-genome sequences were obtained by massively parallel sequencing. Bivariate, multi-variate, and classification and regression tree analyses were run between clinical and genomic variables.

Results: Age >88 years, and infection with lineages B.1.1, B.1.1.388, B.1.523 or B.1.621 for patients aged 71-88 years were associated with death [odds ratio (OR) 6.048036, 95% confidence interval (CI) 1.346567-32.92521; P=0.01718674]. The need for hospitalization was associated with higher age and comorbidities. The hospitalization rate increased significantly for patients aged 38-51 years infected with lineages A, B, B.1.1.388, B.1.1.434, B.1.153, B.1.36.10, B.1.411, B.1.471, B.1.558 or B.1.621 (OR 8.368427, 95% CI 2.573145-39.10672, P=0.00012). Associations between clades and clinical outcomes diverged from previously reported data.

Conclusions: Infection with lineage B.1.621 increased the hospitalization and mortality rates. These findings, plus the rapidly increasing prevalence in Colombia and other countries, suggest that lineage B.1.621 should be considered as a 'variant of interest'. If associated disease severity is confirmed, possible designation as a 'variant of concern' should be considered.

Keywords: COVID-19; High-throughput nucleotide sequencing; Hospitalization; Mortality; SARS-CoV-2; SARS-CoV-2 variants.

Figure 1

Phylogenetic tree of 673 Colombian samples. Most sequences clearly cluster together while the remaining 15 sequences lie in different branches more closely related to the Wuhan strain. The most common lineages are labelled with the following colours: B.1, blue; B.1.111, red; B.1.1.348, yellow; B.1.1, green; B.1.153, olive green; B.1.420, pink. Other colours are described in HTML code in Table S1 (see online supplementary material).

Figure 2

Mosaic plot showing the monthly distribution of Global Initiative on Sharing All Influenza Data (GISAID) clades during the study time window.

Figure 3

Classification and regression tree for mortality. Two variables (age and four lineages) were associated with higher mortality. This tree identifies patients with commonalities, classified into four subgroups. (A) Patients aged >88 years, with mortality rate of 53% (2% of the total study sample). (B) Patients aged 71–88 years who presented with any of the following four lineages: B.1.1, B.1.1.388, B.1.523 or B.1.621. In this group, 62% of patients died (1% of the sample). (C) Patients aged 71–88 years who presented with lineages different from the four described above, and had 21% mortality rate (14% of the sample). (D) Patients aged <71 years, who had 3% mortality rate (84% of the total sample).

Figure 4

Classification and regression tree for hospitalization. The tree seeks to identify the variables determining the clinical severity of coronavirus disease 2019 in terms of the need for hospitalization. Six groups were identified. (A) Patients aged >59 years, with 85% hospitalization rate (36% of the sample). (B) Patients aged 51–59 years with one or more comorbidities, with 73% hospitalization rate (7% of the sample). (C) Patients aged 51–59 years with no comorbidities, with 36% hospitalization rate (6% of the sample). (D) Patients aged 38–51 years with any of the following viral lineages: A, B, B.1.1.388, B.1.1.434, B.1.153, B.1.36.10, B.1.411, B.1.471, B.1.558 or B.1.621, with 82% hospitalization rate (2% of the sample). (E) Patients aged 38–51 years but not presenting any group D lineage, with 35% hospitalization rate (17% of the sample). (F) Patients aged <38 years, with 11% hospitalization rate (31% of the sample).