Genomic monitoring of SARS-CoV-2 variants using sentinel SARI hospital surveillance

Abstract

Background: To support the COVID-19 pandemic response, many countries, including Belgium, implemented baseline genomic surveillance (BGS) programs aiming to early detect and characterize new SARS-CoV-2 variants. In parallel, Belgium maintained a sentinel network of six hospitals that samples patients with severe acute respiratory infections (SARI) and integrated SARS-CoV-2 detection within a broader range of respiratory pathogens. We evaluate the ability of the SARI surveillance to monitor general trends and early signals of viral genetic evolution of SARS-CoV-2 and compare it with the BGS as a reference model.

Methods: Nine-hundred twenty-five SARS-CoV-2 positive samples from patients fulfilling the Belgian SARI definition between January 2020 and December 2022 were sequenced using the ARTIC Network amplicon tiling approach on a MinION platform. Weekly variant of concern (VOC) proportions and types were compared to those that were circulating between 2021 and 2022, using 96,251 sequences of the BGS.

Results: SARI surveillance allowed timely detection of the Omicron (BA.1, BA.2, BA.4, and BA.5) and Delta (B.1.617.2) VOCs, with no to 2 weeks delay according to the start of their epidemic growth in the Belgian population. First detection of VOCs B.1.351 and P.1 took longer, but these remained minor in Belgium. Omicron BA.3 was never detected in SARI surveillance. Timeliness could not be evaluated for B.1.1.7, being already major at the start of the study period.

Conclusions: Genomic surveillance of SARS-CoV-2 using SARI sentinel surveillance has proven to accurately reflect VOCs detected in the population and provides a cost-effective solution for long-term genomic monitoring of circulating respiratory viruses.

Keywords: SARI surveillance; SARS‐CoV‐2; genomic surveillance; influenza; pandemic preparedness; respiratory viruses.

FIGURE 1

Spatial location of the six hospitals from the Belgian hospital‐based SARI surveillance network (BELSARI‐net). (1) AZ Sint Jan Brugge‐Oostende (site Brugge); (2) Universitair Ziekenhuis Brussel; (3) CHU Saint‐Pierre Brussel; (4) Jessa Ziekenhuis Hasselt; (5) GHdC Charleroi; (6) CHU UCL Namur (site Godinne) (map created using the Free and Open Source QGIS, version 3.22.5).

FIGURE 2

SARS‐CoV‐2 VOC dynamics during the COVID‐19 pandemic registered by the SARI surveillance (upper graph) and the national baseline genomic surveillance (lower graph). Both surveillance systems shows similar patterns. The national baseline genomic surveillance officially started in Week 7 of 2021, whereas SARI surveillance sequencing was retrospectively performed since 2020‐W09. The results of the baseline genomic surveillance are based on a total of 96,251 sequences, whereas those of the SARI surveillance system are based on 964 sequences. Wuhan‐like strains and non‐VOC variants (detected in 2020 by SARI surveillance) are included in “other variants.”

FIGURE 3

The maximal weekly detection percentages () in the national genomic baseline surveillance for each of the different VOCs (Alpha, Beta, Gamma, Delta, Omicron, and its relatives) and the slope (● / ○) and R ² (◆) values of linear regression curves for each (see the supporting information) were combined to define an emerging variant. A VOC was considered emerging if complying with the following empirical criteria: R ² > 0.95 (dashed line), slope > 5 (dotted line), and >15% weekly incidence (full line). Based on this definition, Variants B.1.1.7, B.1.617.2, BA.1, BA.2, and BA.5 are considered emerging VOCs, while P.1, BA.3, and BA.4 did not emerge. A slope could not be calculated for VOC B.1.351, as its epidemic growth was not exponential.

FIGURE 4

Comparison of SARS‐CoV‐2 genomic surveillance in SARI samples and the Belgian baseline genomic surveillance. The proportions of the five VOC (B.1.1.7 [Alpha], B.1.351 [Beta], P.1 [Gamma], B.1.617.2 [Delta], and BA.1/BA.2/BA.3/BA.4/BA5 [Omicron]) are presented as the percentage of the total number of weekly sequences from January 2021 (Week 7) until December 2022 (Week 52). Dotted lines with empty triangles represent the SARI genomic surveillance sequences; continuous lines with bullets represent the Baseline Genomic surveillance sequences. For readability reasons, Wuhan‐like strains and non‐VOC variants detected in SARI surveillance in 2020 are not included in the figure. Genomic SARI surveillance shows timely detection for each VOC as compared to the baseline surveillance, except for BA.3 (omicron), which was not detected. The observed trends in the proportion of weekly positives of a variant in SARI surveillance are comparable to the waves observed in the baseline surveillance.