Contribution of low population immunity to the severe Omicron BA.2 outbreak in Hong Kong

Abstract

Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. We hypothesize that Hong Kong's explosive Omicron BA.2 outbreak in early 2022 could be explained by low herd immunity. Our seroprevalence study using sera collected from January to December 2021 shows a very low prevalence of neutralizing antibodies (NAb) against ancestral virus among older adults. The age group-specific prevalence of NAb generally correlates with the vaccination uptake rate, but older adults have a much lower NAb seropositive rate than vaccination uptake rate. For all age groups, the seroprevalence of NAb against Omicron variant is much lower than that against the ancestral virus. Our study suggests that this BA.2 outbreak and the exceptionally high case-fatality rate in the ≥80 year-old age group (9.2%) could be attributed to the lack of protective immunity in the population, especially among the vulnerable older adults, and that ongoing sero-surveillance is essential.

Fig. 1. Cumulative two-dose vaccination uptake rates and neutralization test seropositive rates for ancestral virus and Omicron variant sublineages in 2021.

a–j Cumulative two-dose vaccination rates and neutralization test (NT) seropositive rates of different age groups between January and December 2021. k Two-dose cumulative vaccination uptake rates and neutralization test seropositive rates in November/December 2021. a–k Cumulative vaccination rate represents the percentage of the population that have received 2 doses of COVID-19 vaccines at the end of each time period. Neutralization test seropositive rates represent the percentage of sera tested positive in each time period. All serum specimens were tested with the surrogate virus neutralization test (sVNT) (iFlash-2019-nCoV neutralization antibody assay), which measures antibodies that block the interaction between ancestral virus receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2). Serum specimens tested positive in the sVNT were then tested for NAb against the ancestral virus, Omicron sublineage BA.1 and Omicron sublineage BA.2 using a conventional live virus neutralization test (cVNT). A serum specimen is considered to be seropositive in the sVNT if ≥15 AU/ml, and in the cVNT if the NAb titer is ≥10. The number of serum specimens tested in each period is shown in Supplementary Table S1. For neutralization test seropositive rates, the symbols indicate the mean, and the error bars indicate 95% confidence interval. Source data are provided as a Source Data file.

Fig. 2. Percentage of individuals receiving BNT162b2 or CoronaVac in Hong Kong in 2021.

a–i Percentage of individuals receiving BNT162b2 or CoronaVac for different age groups. The data were extracted from the website of the Food and Health Bureau of Hong Kong. Source data are provided as a Source Data file.

Fig. 3. Comparison of surrogate neutralization activity among different age groups.

a–f Surrogate neutralization activity in different time periods. The horizontal bar indicates the geometric mean level. Dotted horizontal lines represent the manufacturer’s seropositivity cutoff level (15 AU/ml). The geometric mean antibody titer for each age group was compared to the ≥80 years age group using the one way ANOVA with Dunn’s multiple comparisons test. The number of serum specimens tested in each period is shown in Supplementary Table S1. Source data are provided as a Source Data file. NS, not significant.

Fig. 4. Epidemiology and genomic analysis of the fifth wave of COVID-19 in Hong Kong.

a Epidemic curve showing the incidence of COVID-19 cases between December 31, 2021 and March 24, 2022. b Age specific incidence rate of COVID-19 related hospitalization in Hong Kong as of February 24, 2022. c Age specific case-fatality rate of COVID-19 as of March 24, 2022. d Time-resolved phylogenetic tree of 545 viral genomes from Dec 1, 2021 to March 11 2022. BA.1.* includes BA.1.1, BA.1.1.1, BA.1.1.10, BA.1.1.13, BA.1.1.14, BA.1.1.16, BA.1.1.18, BA.1.1.2, BA.1.14, BA.1.15, BA.1.15.1, BA.1.17, BA.1.17.2 and BA.1.18. BA.2.* includes BA.2.2, BA.2.3, and BA.2.10. Details of the sequences used are shown in Supplementary Data 1. Source data are provided as a Source Data file.