E627K In First Confirmed Hangzhou Case

Recombinomics Commentary 19:00
April 15, 2013

The Hangzhou Center for Disease Control and Prevention has now released a full set of sequences from the first case (38M) in Hangzhou, A/Hangzhou/1/2013.  Sequences from H7, N9, and MP were released earlier at GISAID, and are now also available at Genbank.  The release of the remaining five genes was completed this weekend.  As noted previously, the H7 has L226I, which represents further evolution ofQ226L, which was seen in two of the three earlier cases, as well as all three avian sequences.  The three prior human PB2 sequences had E627K, which was not present in any of the three avian sequences.  The PB2 from A/Hangzhou/1/2013 also has E627K.
Thus, the appearance of E627K in all four human cases and none of the three avian sequences raises concerns that this human adapted version is circulating in humans and is producing a wide spectrum of clinical presentations.  However, since all of the human H7N9 sequences are from fatal cases, it is possible that milder cases such as the asymptomatic case in Beijing lack E627K.  However, E627K leads to elevated viral loads in the upper respiratory tract, which was the sample source for A/Hangzhou/1/2013 as well as the asymptomatic case, suggesting that E627K will be in all or most human cases.
If the Beijing sequences match those of the fatal cases in and around Shanghai, then the WHO claims of no sustained transmission would have little support because testing of mild or asymptomatic case contacts has been limited.  Media reports note that much of the contact tracing is via phone interviews which would miss asymptomatic cases and would likely also miss mild cases.
The number of H7N9 confirmed cases is now 64 and 14 of the 15 outcomes have been fatal (case fatality rate of 93%).  This high rate highlights the testing limitations and heavy bias for severe hospitalized cases.  Expanded surveillance is urgently require, which involves actual testing of contacts.  The large number of cases over a wide area and the absence of poultry contact in most cases suggests the H7N9 is currently transmitting human to human in a sustained manner.