Background:After the SARS outbreak in 2003 and occasional cases of Avian Flu later on in Guangzhou, a network for viral surveillance of patients with Flu-like symptoms was established. Once several human cases of infection with pandemic (H1N1) 2009 influenza A virus (pH1N1) were identified on April 2009, a prospective comparative multi-centres follow-up study was conducted to describe variation in viral agents in acute respiratory infection (ARI) patients in different periods during 2009 and to further investigate the clinical characteristics of pHlNl and seasonal influenza infection.Methods:Patients admitted to the First Affiliated Hospital of Guangzhou Medical College, GuangdongProvincial Hospital of Traditional Chinese Medicine (Guangzhou, China) and Ershadao Branch with adiagnosis of ARI or community-acquired pneumonia were prospectively included. The subjects werefollow-up at one and four weeks later. Nasopharyngeal swab was obtained on enrolment for viralisolation or real time-polymerase-chain-reaction for detection of respiratory viruses.Results:Among1498 individuals (with 197 pneumonia cases) enrolled, pH1N1 were identified form 265cases, seasonal influenza A virus from 286 cases (117 seasonal influenza A [H1N1], 162 A [H3N2], and 7could not be subtyped for H1 or H3, respectively), influenza B virus from 137 cases, and seasonal influenzaA and B virus co-infections from 7 cases. Additional 45 non-influenza viruses were tested positive. During2009, influenza B virus was the predominant strain beforeintroduction of pH1N1(Epidemic week, EW1-21), with non-pH1N1 influenza A virus the predominant virus in the input phase(EW 22-27). Howeverthis predominance shifted to pH1N1 from EW 28 to 52. pH1N1 patients were younger than seasonalinfluenza A (H1N1) and A (H3N2) patients (median[IQR] age, 21[16-28] vs 27[21-33] and 28(23-39) years).Logistic regression showed that ORs were 1.04 (95%CI 1.02-1.07, P=.001) and 1.07(95%CI1.05-1.09,P=0.001) for seasonal influenza A (H1N1) and A (H3N2). More cases of patient had sick contactsin pH1N1 2009 group than in two seasonal influenza A group (P<0.001, by X2 test). However, fewsignificant differences were found in clinical symptoms and severity of illness among these three differentinfluenza A strains.Conclusions:The viral distribution in Guangzhou changed upon the introduction of pH1N1 compared withprevious months. pH1N1 mostly affected individuals younger than 30 years, with mild disease.Considering the severe cases accounting for a very small proportion among all pH1N1 infection casessimilar to seasonal influenza A virus. this first pandemic wave was characterized by a mild severity.