The temporal relationship between viral clearance, highest fever, and peak major serum cytokines is shown in Fig. 5. It took a median of 24 days to clear the H7N9 virus based on RT-PCR results of sputum. The highest fever elevation occurred in the first 15 days of fever onset. Significantly elevated serum cytokines mostly occurred before complete clearance of H7N9. Peak IFNc levels also occurred quite early although for some patients, peak occurred at a later time. Serum antibody responses specific to the HA antigen of H7N9 were monitored daily from the day of admission until the time of discharge or at end of the current study period. Three patients had clearly elevated H7 HA-specific antibodies in their sera on the day of admission while three other patients showed a daily increase in H7 HAspecific antibodies starting on the day of admission. This finding suggested that the first three patients may have had a longer period of H7N9 infection before being admitted although, based on the onset of fever, the length of their pre-admission period was relatively similar to the other three patients. It is possible that these patients may have had other clinical symptoms before developing fever so the onset of viral infection may have been longer before their admission. Interestingly, Patients #1�C#3 also had a prolonged clinical course and stayed in the hospital longer compared with the other three patients. Early MLN4924 hospitalization with specific treatment may AG-013736 contribute to a better clinical outcome. Detailed analysis was conducted to determine isotype specificity of H7 HA antibody responses in infected patients. For this analysis, antibody titers were determined by the end titration of serum against H7 HA antigen coated in ELISA plates; daily titers were determined only within the first 20 days of fever onset followed by titers determined every 10 days for the remaining period of hospitalization. The same two subgroups were observed as in the early days after admission. Patients #1�C#3 had an H7 HA-specific IgG titer between 1:104 and 1:105, while the other three patients had low or below detectable levels of H7 HAspecific IgG responses.