H7N9 studies affirm pathogenesis, transmission data

Chinese research teams yesterday reported new findings about the H7N9 flu virus that reveal more about cytokine patterns seen in severely ill patients and affirm again that the virus has the capacity for airborne transmission in a ferret model.

The studies appeared in an early online edition of the Journal of Infectious Diseases.

In the cytokine study, researchers examined serum samples from 16 patients with lab-confirmed H7N9 infections who were hospitalized in Jiangsu province, one of the areas most affected by the virus, during the height of the epidemic this spring.

Blood samples were collected 6 to 9 days after patients became ill, and researchers compared them with serum samples from healthy people and from those who had mild seasonal H3N2 infections and healthy controls.

Of the H7N9 patients, the mean age was 48.5 years, and nine were men. Eleven patients had underlying illnesses, and fever and lower respiratory tract symptoms were the most common clinical findings. Eleven received antivirals, eight got corticosteroids, and five were treated with immunomodulators before they were sampled. Thirteen patients had severe disease, and five of them died.

After measuring cytokine levels in all of the samples, H7N9 infection induced Th1-type and Th17-type cytokines, which suggests an intense response to virus infection that may recruit inflammatory cells to infected tissues, contributing to the severity of the disease, the group reported.

When compared with patients who had less severe illness, the sicker H7N9 patients had higher IP-10 chemokine and IL-6 cytokine levels, which the team said could play a role in tissue destruction and serve as markers for severe disease. They noted that the pattern fits the profile of an intense response to virus infection, as well as one seen with autoimmune and inflammatory disease.

Another recent study of cytokine responses to different flu viruses reported similar findings, that H7N9 provoked a higher response than the 2009 H1N1 virus, but lower than H5N1.

The investigators involved in yesterday's study also found that the pattern was similar to H5N1, SARS, and severe 2009 H1N1 infections, suggesting that IP-10 and IL-6 play a critical role in virus-linked severe respiratory diseases. The findings also hint at a possible role for immunomodulators as a therapy approach to blunt the response.

In the other new study, another team from China conducted a series of experiments to study the pathogenicity and airborne spread of H7N9 in ferrets. In the pathogenicity tests, they inoculated four groups of three ferrets with one of two concentrations of an Anhui H7N9 strain, the 2009 H1N1 virus, or the H5N1 virus.

Infections in H7N9-infected ferrets were less severe than in those inoculated with H5N1, but were similar to those sickened with the 2009 H1N1 virus. Researchers also found that H7N9 could replicate in the ferrets' upper and lower respiratory tracts, heart, liver, and olfactory bulb.

To test transmissibility, they inoculated three ferrets each in two groups with either H7N9 or H5N1. The next day they placed each animal in a cage adjacent to a never-infected ferret, collecting nasal and throat swabs and odd-numbered days postexposure. The H7N9 virus spread by the airborne route to one of three experimental animals. No transmission was seen in the in the animals placed next to the H5N1-infected ferrets.

The team wrote that the findings suggest the virus can spread by respiratory droplets, though at low levels, given that transmission only occurred in one third of tested animals.

The results seem to confirm other recent studies in ferrets, which showed that H7N9 can transmit by the airborne route in ferrets, but not very efficiently.

Chi Y, Zhu Y, Wen T, et al. Cytokine and chemokine levels in patients infected with the novel avian influenza A (H7N9) virus in China. J Infect Dis 2013 Aug 29 [Abstract]

Xu L, Bao L, Deng W, et al. The novel avian-origin human A (H7N9) influenza virus could be transmitted between ferrets via respiratory droplets. J Infect Dis 2013 Aug 29 [Abstract]

See also:

Jul 25 CIDRAP News story "H7N9 study in human airway tissue adds to pandemic concerns"

May 23 CIDRAP News story "Study: H7N9 shows limited aerosol transmission in ferrets"

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