Dr TO, Kelvin Kai-Wang

 

BSc, MBBS, FRCPath, FHKCPath, FHKAM (Pathology), FRCP (Edin), MD

 

Clinical Associate Professor, Department of Microbiology


Email: kelvinto@hku.hk

 

ORCID : https://orcid.org/0000-0002-1921-5824

 

 

Research Interests

Respiratory tract infection is one of the leading causes of morbidity and mortality worldwide. Our research seeks to improve outcome of patients with respiratory tract infections through better understanding of pathogenesis, development of more refined diagnostics, and optimization of clinical management, as well as to reduce the burden of respiratory tract infections in the community and in hospitals. In particular, we focus on influenza virus (including pandemic and avian influenza viruses) and rhinovirus because these respiratory viruses are often associated with severe infective or non-infective complications. Our strategies include:

1. Elucidation of the pathogenesis and pathophysiology of respiratory tract infections (host genetic susceptibility; host response);

2. In-depth understanding of pulmonary and extrapulmonary complications of respiratory tract infections;

3. Study of the epidemiology of severe respiratory tract infections;

4. Development of better diagnostic tests for respiratory tract infections;

5. Identification of novel treatment strategies, including antivirals and immunomodulators;

6. Development of novel vaccine strategies.

 

Selected Publications

Clinical and epidemiological studies

1. To KK, Hung IF, Li IW, Lee KL, Koo CK, Yan WW, Liu R, Ho KY, Chu KH, Watt CL, Luk WK, Lai KY, Chow FL, Mok T, Buckley T, Chan JF, Wong SS, Zheng B, Chen H, Lau CC, Tse H, Cheng VC, Chan KH, Yuen KY. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis. 2010 Mar 15;50(6):850-9.

2. Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, Yao H, Wo J, Fang Q, Cui D, Li Y, Yao X, Zhang Y, Wu H, Zheng S, Diao H, Xia S, Zhang Y, Chan KH, Tsoi HW, Teng JL, Song W, Wang P, Lau SY, Zheng M, Chan JF, To KK, Chen H, Li L, Yuen KY. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet. 2013 Jun 1;381(9881):1916-25. doi: 10.1016/S0140-6736(13)60903-4.

3. To KK, Song W, Lau SY, Que TL, Lung DC, Hung IF, Chen H, Yuen KY. Unique reassortant of influenza A(H7N9) virus associated with severe disease emerging in Hong Kong. J Infect. 2014 Jul;69(1):60-8. doi: 10.1016/j.jinf.2014.02.012.

4. To KK, Lau SK, Chan KH, Mok KY, Luk HK, Yip CC, Ma YK, Sinn LH, Lam SH, Ngai CW, Hung IF, Chan KH, Yuen KY. Pulmonary and extrapulmonary complications of human rhinovirus infection in critically ill patients. J Clin Virol. 2016 Apr;77:85-91. doi: 10.1016/j.jcv.2016.02.014.

5. To KK, Hung IF, Lui YM, Mok FK, Chan AS, Li PT, Wong TL, Ho DT, Chan JF, Chan KH, Yuen KY. Ongoing transmission of avian influenza A viruses in Hong Kong despite very comprehensive poultry control measures: A prospective seroepidemiology study. J Infect. 2016 Feb;72(2):207-13. doi:10.1016/j.jinf.2015.10.013.

6. Hung IF, Zhang AJ, To KK, Chan JF, Zhu SH, Zhang R, Chan TC, Chan KH, Yuen KY. Unexpectedly Higher Morbidity and Mortality of Hospitalized Elderly Patients Associated with Rhinovirus Compared with Influenza Virus Respiratory Tract Infection. Int J Mol Sci. 2017 Jan 26;18(2). pii: E259. doi:10.3390/ijms18020259.

 

Diagnostic tests

1. To KK, Lu L, Yip CC, Poon RW, Fung AM, Cheng A, Lui DH, Ho DT, Hung IF, Chan KH, Yuen KY. Additional molecular testing of saliva specimens improves the detection of respiratory viruses. Emerg Microbes Infect. 2017 Jun 7;6(6):e49. doi: 10.1038/emi.2017.35.

2. To KK, Wong SC, Xu T, Poon RW, Mok KY, Chan JF, Cheng VC, Chan KH, Hung IF, Yuen KY. Use of nasopharyngeal aspirate for diagnosis of pneumocystis pneumonia. J Clin Microbiol. 2013 May;51(5):1570-4. doi: 10.1128/JCM.03264-12.

3. To KK, Lee KC, Wong SS, Sze KH, Ke YH, Lui YM, Tang BS, Li IW, Lau SK, Hung IF, Law CY, Lam CW, Yuen KY. Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia. Diagn Microbiol Infect Dis. 2016 Jun;85(2):249-54.

 

Pathogenesis and host genetic susceptibility

1. To KK, Zhou J, Song YQ, Hung IFN, Ip WC, Cheng ZS, Chan AS, Kao RY, Wu AK, Chau S, Luk WK, Ip MS, Chan KH, Yuen KY. Surfactant protein B gene polymorphism is associated with severe influenza. Chest. 2014 Jun;145(6):1237-1243. doi: 10.1378/chest.13-1651.

2. Zhang AJ, To KK, Li C, Lau CC, Poon VK, Chan CC, Zheng BJ, Hung IF, Lam KS, Xu A, Yuen KY. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J Infect Dis. 2013 Apr 15;207(8):1270-80. Doi: 10.1093/infdis/jit031.

3. Zhou J, To KK, Dong H, Cheng ZS, Lau CC, Poon VK, Fan YH, Song YQ, Tse H, Chan KH, Zheng BJ, Zhao GP, Yuen KY. A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection. J Infect Dis. 2012 Aug 15;206(4):495-503. doi: 10.1093/infdis/jis378.

4. To KK, Zhang AJ, Hung IF, Xu T, Ip WC, Wong RT, Ng JC, Chan JF, Chan KH, Yuen KY. High titer and avidity of nonneutralizing antibodies against influenza vaccine antigen are associated with severe influenza. Clin Vaccine Immunol. 2012 Jul;19(7):1012-8. doi: 10.1128/CVI.00081-12.

 

Treatment

1. Hung IFN, To KKW, Chan JFW, Cheng VCC, Liu KSH, Tam A, Chan TC, Zhang AJ, Li P, Wong TL, Zhang R, Cheung MKS, Leung W, Lau JYN, Fok M, Chen H, Chan KH, Yuen KY. Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial. Chest. 2017 May;151(5):1069-1080. doi: 10.1016/j.chest.2016.11.012.

2. Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CCY, Liu SH, Chan KH, Lin CK, Yuen KY. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-473. doi: 10.1378/chest.12-2907.

3. To KK, Mok KY, Chan AS, Cheung NN, Wang P, Lui YM, Chan JF, Chen H, Chan KH, Kao RY, Yuen KY. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans. J Gen Virol. 2016 Aug;97(8):1807-17. doi:10.1099/jgv.0.000512.

 

Vaccine

1. Hung IF, Zhang AJ, To KK, Chan JF, Li P, Wong TL, Zhang R, Chan TC, Chan BC, Wai HH, Chan LW, Fong HP, Hui RK, Kong KL, Leung AC, Ngan AH, Tsang LW, Yeung AP, Yiu GC, Yung W, Lau JY, Chen H, Chan KH, Yuen KY. Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial. Lancet Infect Dis. 2016 Feb;16(2):209-18. doi: 10.1016/S1473-3099(15)00354-0.

2. To KK, Zhang AJ, Chan AS, Li C, Cai JP, Lau CC, Li CG, Jahan AS, Wu WL, Li L, Tsang AK, Chan KH, Chen H, Yuen KY. Recombinant influenza A virus hemagglutinin HA2 subunit protects mice against influenza A(H7N9) virus infection. Arch Virol. 2015 Mar;160(3):777-86. doi: 10.1007/s00705-014-2314-x.

 

Reviews

1. To KK, Chan JF, Chen H, Li L, Yuen KY. The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities. Lancet Infect Dis. 2013 Sep;13(9):809-21. doi: 10.1016/S1473-3099(13)70167-1.

2. To KK, Zhou J, Chan JF, Yuen KY. Host genes and influenza pathogenesis in humans: an emerging paradigm. Curr Opin Virol. 2015 Oct;14:7-15. doi:10.1016/j.coviro.2015.04.010.

3. To KK, Yip CC, Yuen KY. Rhinovirus - From bench to bedside. J Formos Med Assoc. 2017 Jul;116(7):496-504. doi: 10.1016/j.jfma.2017.04.009.