Characteristics of the omicron XBB subvariant wave in Singapore.

The XBB sublineage of the omicron (B.1.1.529) variant of SARS-CoV-2 was first identified in India in August, 2022, and has since spread rapidly around the world.1Ministry of Health SingaporeUpdate on COVID-19 situation and measures to protect healthcare capacity.https://www.moh.gov.sg/news-highlights/details/update-on-covid-19-situation-and-measures-to-protect-healthcare-capacityDate: Oct 15, 2022Date accessed: October 27, 2022Google Scholar, 2Cepeda M Philippines detects first cases of XBB COVID-19 sub-variant, XBC recombinant. The Straits Times.https://www.straitstimes.com/asia/se-asia/philippines-detects-first-cases-of-xbb-covid-19-sub-variant-xbc-recombinantDate: Oct 18, 2022Date accessed: October 27, 2022Google Scholar A recombinant of the BA.2.10.1 and BA.2.75 sublineages,3WHOWeekly epidemiological update on COVID-19—26 October 2022. Edition 115.https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19--26-october-2022Date: Oct 26, 2022Date accessed: October 27, 2022Google Scholar, 4WHOTracking SARS-CoV-2 variants.https://www.who.int/activities/tracking-SARS-CoV-2-variantsDate: Oct 27, 2022Date accessed: October 27, 2022Google Scholar, 5WHOTAG-VE statement on omicron sublineages BQ.1 and XBB.www.who.int/news/item/27-10-2022-tag-ve-statement-on-omicron-sublineages-bq.1-and-xbbDate: Oct 27, 2022Date accessed: October 27, 2022Google Scholar early studies6Cao Y Jian F Wang J et al.Imprinted SARS-CoV-2 humoral immunity induces convergent omicron RBD evolution.Nature. 2023; 614: 521-529PubMed Google Scholar, 7Kurhade C Zou J Xia H et al.Low neutralization of SARS-CoV-2 omicron BA.2.75.2, BQ.1.1, and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster.Nat Med. 2023; 29: 344-347Crossref PubMed Scopus (53) Google Scholar suggested that XBB was one of the most immune-evasive strains tested. However, whether the growth advantage of XBB was sufficient to outcompete other SARS-CoV-2 strains and drive new waves of infection was unclear. The Ministry of Health of Singapore monitors circulating SARS-CoV-2 variants through a national acute respiratory infection surveillance system that includes genomic surveillance. Compared with the omicron subvariants that dominated previous waves of infection in the country (BA.2 in March, 2022, and BA.5 in July, 2022), XBB showed considerably steeper growth—becoming predominant in less than 1 month (compared with 2 months for BA.5), outcompeting the BA.2.75 subvariant that was also increasing in case proportions, and propelling an infection wave in Singapore. We aimed to characterise the traits of the XBB sublineage and compare them with those of other SARS-CoV-2 strains. When the first imported case of XBB infection was detected on Sept 6, 2022, case numbers in Singapore were relatively low and three major omicron subvariants were co-circulating: BA.5 (calculated at 86% of community cases on the basis of S-gene target failure testing and whole-genome sequencing), BA.2.75 (11% of cases, an increase from 0·4% when the first case was detected on July 9, 2022), and BA.2 (3% of cases). By the week commencing Sept 26, 2022, XBB accounted for an estimated 22% of community cases, increasing to 54% the following week and 75% by the week commencing Oct 10, 2022; a sharp increase in case numbers was also reported (figure). We compared the incidence of severe COVID-19 (defined as requiring oxygen supplementation, admission to an intensive care unit, or death within 30 days of a positive test) among all people with first SARS-CoV-2 infections during four waves of infection in Singapore—dominated by delta (B.1.617.2), omicron BA.1 or BA.2, omicron BA.4 or BA.5, and omicron XBB subvariants—between June 1, 2021, and Nov 15, 2022. After adjusting for age, sex, ethnicity, housing type (as a proxy for socioeconomic status), vaccination status, and time since last vaccine dose using a Poisson regression model, we found that individuals infected in the XBB wave were at lower risk of severe COVID-19 than those infected in the delta wave (incidence rate ratio 0·68; 95% CI 0·60–0·76; appendix). These findings, based on comprehensive national data, suggest that infection with XBB results in less severe disease than infection with the delta variant and similar disease severity to infection with omicron BA.4 and BA.5 subvariants. XBB probably also drove the observed increase in SARS-CoV-2 reinfections between Sept 26 and Oct 18, 2022, in which the 7-day moving average proportion of reinfections among confirmed COVID-19 cases increased from 8·2% to 18·8%. Reinfection was defined as a positive test at least 90 days after the last positive test in the same individual. A separate national cohort study8Tan CY Chiew CJ Pang D Protective immunity of SARS-CoV-2 infection and vaccines against medically attended omicron BA.4, BA.5, and XBB reinfection in Singapore: a national cohort study.Lancet Infect Dis. 2023; (published online March 13.)https://doi.org/10.1016/S1473-3099(23)00060-9Summary Full Text Full Text PDF Scopus (2) Google Scholar found that previous infection with pre-omicron variants did not confer protection against XBB reinfection compared with SARS-CoV-2-naive individuals, whereas previous infection with omicron BA.1 or BA.2 subvariants conferred low to moderate protective immunity against XBB reinfection (up to 51%), especially when combined with vaccination for hybrid immunity. This finding could reflect improved immunity against XBB conferred by infection with the better-matched omicron subvariants. The evolution of the omicron variant continues to drive the emergence of new subvariants. In Singapore, the growth advantage of XBB over BA.5 and BA.2.75 was clear, particularly as the proportion of BA.2.75 infections increased from 11% to 35% during the 4 weeks after the country's first imported XBB case. By Nov 1, 2022—2 weeks after the peak of the XBB wave in Singapore—a stable equilibrium had been reached between XBB, BA.5, and BA.2.75 co-circulating in the community. Hybrid immunity from high vaccination rates and previous infection, as well as the availability of antivirals, probably helped to maintain low disease severity; however, as one of the most immune-evasive subvariants to date, XBB still drove a new wave of infections. Many countries have not had XBB waves or do not have the same extent of hybrid immunity in their populations as Singapore, and the prevalent strains of SARS-CoV-2 might vary in different regions of the world as the virus rapidly mutates—for example, European countries are seeing an increase in cases due to the omicron BQ.1 subvariant. This pattern of highly immune-evasive strains resulting in epidemic waves with large numbers of reinfections could be increasingly common in the future. Singapore's experience underscores the importance of continued vigilance to ensure that new subvariants are rapidly characterised, especially now that the lead time for public health responses has been reduced by increased virus transmissibility, the resumption of international travel, and the reopening of societies. We declare no competing interests. Download .pdf (.37 MB) Help with pdf files Supplementary appendix