Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain)

Abstract

ABSTRACTThe emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher's exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p = 2.89 × 10^-25; vs. BA.1 p = 5.17 × 10^-11; vs. BA.2 p = 0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] = 0.45, 95% Confidence Interval [CI] = 0.23-0.87, p = 0.02), BA.2 (OR = 0.38, 95% CI = 0.22-0.63, p = 1.91 × 10^-4), and BA.5 (OR = 0.30, 95% CI = 0.16-0.55, p = 1.05 × 10^-4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern.

Keywords: Omicron lineage; SARS-CoV-2; disease severity; reinfection; variants of concern.

Figure 1.

14-day accumulated incidence (AI) and variants observed in the Canary Islands from December 2020 to July 2022. Note that, from the end of March 2022 (red dotted vertical line), only samples from >60 years old or hospitalized patients were sequenced and included in the 14-days AI calculation by public health authorities. Black line, 14-days AI.

Figure 2.

Proportion of reinfections observed in the Canary Islands by lineage. The proportion of reinfections was calculated as the number of reinfections by lineage divided by the total number of infections by that lineage. Pairwise proportions tests with post hoc Holm correction were applied. Only p values between BA.5 and the other lineages are shown. Error bars represent the standard error of sample proportion.

Figure 3.

Proportion of primary infections in lineage-causing reinfections. Each panel encompasses the lineage causing the secondary infection and each bar represents the number of reinfection cases by lineage causing the primary infection normalized by the total number of cases assigned to that lineage throughout the study period. Fisher’s exact tests with post hoc Holm correction were applied to test the significance of the intra-group differences. Only significantly different comparisons are shown. Error bars represent the standard error of sample proportion. Reinfection cases with primary infection with n = 1 were excluded.

Figure 4.

Maximum likelihood phylogenetic tree of SARS-CoV-2 sequences (radial) placing the sequences from 1,144 hospitalized cases with infections in the Canary Islands throughout the study period. The tree also includes relationships with other 1,504 genome sequences representative of major clades (light grey), labelled based on Nextstrain definitions, from Nextclade v2.13.0 and Auspice v2.24.2 (as of 2023-03-24), and sampled between December 2019 and July 2022 for reference.

Figure 5.

Forest plots of the 28-day hospital mortality associated with the presence of a variant of concern compared to Delta. The upper panel shows the estimated odds ratio (OR) and the 95% confidence interval (CI) from the logistic regression analysis. The lower panel shows the hazard ratio (HR) and the 95% CI from the Cox regression analysis. P-values are also reported.