A recent report posted to the Research Square* preprint server illustrated that inadequate population immunity exacerbated the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage outbreak in Hong Kong.
SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is known for its rapid person-to-person transmission, the tendency for causing severe illness, and the generation of mutants that evade population immunity. Although the strict non-pharmaceutical COVID-19 measures imposed by nations worldwide have limited SARS-CoV-2 spread, these measures have led to undesirable socioeconomic and mental health implications.
Forecasting the intensity of future COVID-19 waves is a critical part of developing public health preparedness strategy. Tracking protective immunity in the population against the SARS-CoV-2 variants imparted by COVID-19 or its vaccination could aid the ability to estimate the impact of SARS-CoV-2 on the public health system. SARS-CoV-2 serosurveillance employing neutralizing antibody (NAb) evaluations is beneficial for determining the amount of protective immunity in a community.
The serosurveillance assessments in Hong Kong conducted by the authors of the present study have reported that less than 1% of serum samples obtained from the population were SARS-CoV-2-positive before March 2021. Nonetheless, the COVID-19 seropositivity rates began to hike from April 2021.
About the study
In the current serosurveillance investigation, the scientists profiled 1800 serum specimens retrieved from the clinical biochemistry laboratory of the Queen Mary Hospital, Hong Kong, procured between January and December 2021 for COVID-19 positivity using a surrogate virus neutralization test (sVNT). The sVNT had a strong correlation with the conventional live virus neutralization test (cVNT) against the SARS-COV-2 ancestral strain.
Furthermore, the sVNT-derived SARS-CoV-2-positive serum samples were further analyzed using a cVNT to assess the NAb titers against the SARS-CoV-2 ancestral strain and Omicron BA.2 and BA.1 sublineages. The authors evaluated the current serosurveillance findings with the genomic and epidemiological data of the fifth SARS-CoV-2 wave in Hong Kong, which had surpassed one million COVID-19 patients by March 18, 2022.
The researchers collected roughly the same number of anonymized serum specimens depending on the availability from each 10-year age cohort ranging from zero to nine to ≥80 years old. In total, 300 serum specimens were selected and tested randomly at each two-month timepoint from January/February to November/December 2021. The specimens with inadequate serum volume were excluded from the analysis.
Results and discussions
The study results showed that even though the COVID-19 cumulative two-dose vaccine uptake rate in Hong Kong had surpassed 60% by November 2021, just 30% of the research population had a SARS-CoV-2-positive sVNT. Furthermore, the NAb titers against the SARS-CoV-2 Omicron BA.2 and BA.1 sublineages were detected in only 7.3% and 2.3%, respectively.
In the sVNT results, the SARS-CoV-2 seropositivity rate was remarkably comparable with the COVID-19 two-dose cumulative vaccination rate in the 20 to 29 and 10 to 19-year age cohorts. On the other hand, older individuals had a significant disparity between SARS-CoV-2 vaccination and the sVNT seropositive rates, which the researchers believe was due to a lower immune response in this age cohort.
Another factor influencing the low SARS-CoV-2 seropositive rate in older people was their COVID-19 vaccine preference. More than half of the study population aged ≥60 years opted for the CoronaVac vaccine. CoronaVac recipients reported lower seropositive rates than BNT162b2 recipients in a head-to-head analysis. Furthermore, the seropositive rate for CoronaVac vaccinees dropped faster than for BNT162b2 recipients. These findings support the advice of the World Health Organization that older people should receive three CoronaVac doses.
Older people displayed the lowest rates of COVID-19 protective immunity. None of the persons in the ≥80-year-old age group had a SARS-CoV-2-positive sVNT, and just 12% of the 70 to 79-year-old age cohort had detectable NAb titers against BA.2 or BA.1. Additionally, none of the participants in the ≥70-year-old age category had detectable NAb titers against the Omicron BA.2 or BA.1 sublineages. The case-fatality rate in the ≥80 years cohort was 9.2% in the fifth SARS-CoV-2 wave in Hong Kong.
Since SARS-CoV-2 incidence in Hong Kong was very low due to the elimination strategy, the NAb titers detected by either cVNT or sVNT in most subjects were possibly induced by COVID-19 vaccination instead of by viral infection. As expected, no serum specimens in the zero to nine years age cohort were SARS-CoV-2-positive in the sVNT since COVID-19 vaccination for this group was not initiated in Hong Kong during the study period.
In November/December 2021, there was a decline in seropositive rates, accompanied by a low vaccination uptake rate after September, indicative of the waning effect of vaccine-induced SARS-COV-2 protection. Further, BA.2 NAb titers were usually higher than BA.1 NAb titers in the test subjects.
Altogether, the absence of protective immunity against the Omicron BA.2 sublineage, particularly among the elderly, probably contributed to Hong Kong’s devastating fifth COVID-19 wave, which expanded rapidly in February 2022 and overwhelmed the medical system.
The study findings illustrated that older persons had significantly lower frequencies of NAb seropositivity against the ancestral SARS-CoV-2 sequence than younger people. The rate of NAb seropositivity rises in lockstep with the vaccine uptake rate in the general population. Yet, older people have a substantially lower NAb seropositivity rate than the vaccination uptake rate.
Further, the NAb seropositive frequencies against the SARS-CoV-2 Omicron variant were much less than those against the ancestral viral strain in all age categories. The case-fatality rate in the 80 years or older cohort was unusually high during the fifth COVID-19 wave in Hong Kong, which was dominated by the Omicron BA.2 sublineage.
On the whole, the present work implies that in Hong Kong, the catastrophic SARS-CoV-2 Omicron BA.2 outbreak was caused by the absence of protective immunity in the community, specifically among the susceptible elderly populations, and emphasizes the significance of the ongoing protective immunity surveillance against the evolving SARS-CoV-2 variants.
Research Square publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.