Focusing his research on influenza viruses throughout his career, Guan has identified all the major precursors and transmission pathways of the H5N1 variant that circulates in Southeast Asia, Europe and Africa and has provided most of the World Health Organization recommended pre-pandemic H5N1 vaccines strains. Guan has, also, initiated the systematic study of H9N2 viruses, which, along with H5 viruses that are now regarded as the most likely novel influenza subtypes to cause a pandemic. Guan has defined the role of domestic ducks in harboring and spreading influenza viruses and made major contributions in recognizing the emergence, evolutionary history and development of the 2009 H1N1 pandemic virus and revealed the genesis, infection source, evolutionary pathway and possible transmission route of the 2017 emerging H7N9 influenza virus. Guan has also contributed to the identification of animal reservoirs for coronaviruses, leading a team to identify bats as a reservoir host for SARS-CoV and palm civets as an intermediate host for SARS-CoV.
COVID-19 pandemic
Guan Yi has given expert comments on SARS-CoV-2 when interviewed by Caixin, warning that the coronavirus could be 10 times worse than the 2003 Sars outbreak. He said to media, ""I have been through so many , and I have never been scared. Most are manageable, but this time I am scared." What he said in his interview with Caixin were apparently different from that in most Chinese media, and it became highly controversial as journalists of state media reposted his previous statement, which he made on 15 January, claiming that the disease was manageable. The journalists also reposted the information that Guan's lab was once fined by the government in 2005. Wang Duan, the Caixin journalist who interviewed Guan Yi, described such behavior as "personal attacks" and complained that no expert had so far come forward to refute what Guan said. Guan Yi didn't give interview since 23 January. In mid July when a cluster of resurgent cases in Beijing was reported, Guan was interviewed by iNewsweek journal （中国新闻周刊） which shared his supportive opinion to the speculation that the virus imported into Beijing via contaminated frozen salmon fishes.
Appearances in popular media
In 2005, Time featured Guan as one of its 18 "Global Health Heroes", and in 2006, named him an "Asian Hero" for his influenza virus research work.
