A child with acute respiratory distress syndrome caused by avian influenza H3N8 virus

Recently in this Journal, Li and colleagues showed that wild bird-origin H3N8 avian influenza virus can potentially adapt well to a mammalian host []. This suggests that H3N8 virus may pose a potential threat to human health. Several previous studies have also shown that H3N8 virus are associated with persistent infection outbreaks in dogs and horses, and have been isolated from pigs, donkeys, and most recently seals [, , ]. A case of acute respiratory distress syndrome in children caused by H3N8 influenza virus has been identified (Fig. 1).

A 4-year-old boy with no significant medical history was transferred to the pediatric intensive care unit of Henan Provincial People's Hospital on April 10, 2022. His chief complaints were fever, drowsiness for 5 days, cough for 2 days, dyspnea for 1 day and 5 h after extracorporeal membrane oxygenation (ECMO). Two days before admission, the child came to the local hospital, where he was considered to have community-acquired pneumonia and received antibiotics and aerosol therapy. One day before admission, the child developed dyspnea and hypoxemia, and was transferred to Zhumadian Central Hospital for endotracheal intubation and ventilator assisted breathing. On April 10, alveolar lavage fluid and peripheral blood samples were taken for metagenomics next-generation sequencing(mNGS). Chest CT showed pneumonia in the upper and lower lobe of the right lung and left lung (Fig. 2A). After 1 day of treatment with antibiotics and "oseltamivir", the fluctuation of blood oxygen saturation under high ventilator parameters was 60–80%, and the oxygenation index was 50. ECMO was recommended. With the consent of the children's parents, the ECMO team of our hospital rushed to the local hospital for femoral vein-internal jugular vein ECMO catheterization 5 h before admission to our hospital. The mNGS results of the bronchoalveolar lavage fluid and peripheral blood samples collected on April 10 showed that 7,888,701 reads suspected H3N8 viruses were detected in the bronchoalveolar lavage fluid and 192 reads in the blood. After admission, patients were given ECMO combined with ventilator for assisted respiration,"oseltamivir" for antiviral, "meropenem" for anti-infection, "methylprednisolone sodium succinate" to reduce inflammation, "plasma and immunoglobulin" infused and other treatments. On April 12, bronchoalveolar lavage was performed again. The mNGS re-examination showed 183 reads virus sequences in the bronchoalveolar lavage fluid, and no virus sequences was detected in the blood. Part of bronchoalveolar lavage fluid sample was sent to the Center for Disease Control and Prevention. Whole genome sequencing confirmed the positive for avian H3N8 influenza virus, and H3N8 influenza virus was successfully isolated from the bronchoalveolar lavage fluid. On April 19, chest CT showed extensive interstitial changes and consolidation in the lungs, with obvious small airway involvement(Fig. 2B). Multiple deep lavage was performed with bronchoscope with an outer diameter of 2.8 mm. On April 20, the number of virus sequences in the bronchoalveolar lavage fluid decreased to 10 reads, and no virus was detected in peripheral blood. The child is in critical condition and is still receiving ECMO combined with ventilator support so far.

In 2014, Karlsson et al. found that the H3N8 avian influenza virus isolated from seals showed high affinity for mammalian receptors, could be transmitted via respiratory droplets, and could replicate efficiently in human lung cells in vitro []. Later studies by Hussein et al. also confirmed that seal H3N8 virus and bird H3N8 virus can bind to human lung tissue and replicate in human lung cancer cells []. These studies suggest the possibility of H3N8 virus transmission to humans. This case is the first human case of H3N8 infection. Fortunately, so far, no other cases of infection have been found in close contact with the child.

This patient started with mental symptoms of fever and lethargy, and then developed severe acute respiratory distress syndrome in a short period of time. The H3N8 virus can still be detected in the lavage fluid on the 11th day of admission, which is similar to other severe avian influenza such as H7N9, and the clearance rate in the body is slower. Pan et al. found that the time from the onset of infection to the virus turning negative in 13 cases of severe human infection with H7N9 avian influenza was (15.9 ± 6.4) days, and the time from antiviral treatment to the virus turning negative was (9.8 ± 7.4) days []. In this case, chest CT review on the 9th day of admission revealed partial pulmonary fibrosis, which may be related to the pulmonary interstitial and diffuse alveolar damage caused by virus. When healthy female mice were infected with H3N8 virus, the lung tissue of mice showed progressively aggravated interstitial inflammatory hyperemia at 3 and 6 days after infection []. There are no reports on lung imaging of H3N8-related cases, but some studies have shown that the absorption time of severe H7N9 avian influenza lesions is more than 1 month, and residual fibrotic lesions such as grid-like or cord-like are still gradually absorbed in patients with 1-year follow-up []. This suggests that even if the patient in this case can be cured and discharged, it is still necessary to follow up the child's imaging prognosis for a long time.