Ruopeng Xie1,2,6, Kimberly M. Edwards1,2,6, Dillon C. Adam1, Kathy S.M. Leung1, Shreya Gurung1,2, Xiaoman Wei1,2, Daisy Y.M. Ng1, Gigi Y.Z. Liu1, Pavithra Krishnan1, Lydia D.J. Chang1, Samuel M.S. Cheng1, Haogao Gu1, Gilman K.H. Siu3, Joseph T. Wu1,4, Gabriel M. Leung1,4, Malik Peiris1,5, Benjamin J. Cowling1,4, Leo L.M. Poon1,2,5, Vijaykrishna Dhanasekaran1,2,*

1School of Public Health, LKS Faculty of Medicine, The University of Hong Kong; Hong Kong S.A.R., China.

2HKU-Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong; Hong Kong S.A.R., China

3Department of Health Technology and Informatics, The Hong Kong Polytechnic University; Hong Kong S.A.R., China.

4Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, New Territories, Hong Kong S.A.R., China

5Centre for Immunology & Infection, Hong Kong Science and Technology Park, New Territories, Hong Kong S.A.R., China.

6These authors contributed equally: Ruopeng Xie, Kimberly M. Edwards.

*Corresponding author:

Vijaykrishna Dhanasekaran, Associate Professor

School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

email: [email protected]

Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analysing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproductive number (Re) increased again during the Chinese New Year in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.