Community-based Sero-epidemiological Study of COVID-19 to Provide Data in Real Time on Age-stratified Infection Attack Rates, Disease Severity and Population Immunity, for Guiding Intervention Policy

Since December 2021, the SARS-CoV-2 B.1.1.529 (Omicron) variant started spreading in Hong Kong, leading to an unprecedented 5th wave. It is known that the Omicron variant may partially evade immunity from past vaccination and infection although both appear to protect from severe disease and death. As Hong Kong emerges from the 5th wave, it will be critically important for public health policy to assess the proportion of the population with evidence of natural infection and those with evidence of detectable neutralizing antibody to the Omicron variant, either though natural infection or vaccination. Our project aims to assess these parameters.

The investigators recruited healthy blood donors by convenience sampling at the five largest blood donation centres (Mongkok, Causeway, Kwun Tong, Tsuen Wan and Shatin) of the Hong Kong Red Cross Blood Transfusion Service (HKRCBTS). Blood donors were matched by the HKRCBTS and the Hong Kong Department of Health with official vaccination records via unique Blood Transfusion Service donor identification numbers. The records were then anonymised and provided to the study team. Blood donors were also provided with the option of self-reporting their vaccination and COVID-19 infection history.

Since the investigators need to distinguish past infection from vaccine induced immunity, they used serological test strategies that would differentiate natural infection from vaccine immunity. The investigators have previously shown that IgG antibody to the Nucleocapsid protein of SARS-CoV-2 (whole protein and the C-terminal domain) provides evidence of past infection and is not elicited by BNT162b2 vaccine but may be elicited by CoronaVac vaccine (Wu et al. 2021, Mok et al. 2021) . They have also shown IgG antibody to ORF8 is elicited by past infection and not by either CoronaVac or BNT162b2 (Hachim et al. 2020). The investigators used these assays to assess evidence of natural infection in blood donor samples.

Through the above procedures, the investigators obtained detailed serial cross-sectional (weekly between mid-April and the end of July, followed by monthly until the end of 2022) estimates of the age-specific distribution of SARS-CoV-2 Omicron variant-specific antibody positivity levels. The investigators derived age-specific infection attack rates and age-specific population immunity levels and tracked the magnitude of individual-level and population-level waning immunity over time.