China faces the challenge of influenza A virus, including H3N8, in the post-COVID-19 era

Dear Editor,

Recently, an article in your journal reported the first human case of the novel H3N8 avian influenza virus (AIV) in Henan Province, China¹; the same year, another case of H3N8 subtype infection was reported in Hunan Province, China.² One of the two patients had acute respiratory distress syndrome, and the other had a mild condition. Moreover, the World Health Organization (WHO) reported a fatal human infection with H3N8 AIV on April 11, 2023, the first known human death caused by H3N8. The patient was a 56-year-old woman from Guangdong Province, China, who was hospitalized with severe pneumonia on March 3 and died on March 16, 2023.

As the WHO reported, nucleic acid tests of environmental samples collected from the house and live poultry markets visited by the deceased patients were positive for H3N8 AIV. Initial epidemiological investigations have indicated that exposure to live poultry markets is a likely cause of H3N8 infection. However, the exact source of the infection and how the virus relates to other H3N8 AIVs circulating among animals remains unclear. No new cases were detected among close contacts or co-exposed individuals associated with the three known cases, suggesting a low H3N8 transmission risk and limited human-to-human infectivity at this stage. H3N8 AIV is prevalent among animals worldwide and is one of the most common subtypes infecting birds.³ The cross-species transmission of H3N8 AIV has been reported in various mammalian species, including dogs and horses.⁴ Our previous study confirmed that H3N8 could induce adaptive mammalian mutations.⁵ AIV transmission from birds to humans is usually sporadic and occurs in specific contexts, mostly from contact with infected poultry or contaminated environments. However, owing to the widespread prevalence of this virus, more sporadic cases are expected in the future.

AIVs mainly circulate among birds and need to be mutated for human infection to cause an epidemic among humans. Currently, it is difficult for most AIVs to infect humans and adapt for effective replication. However, influenza A viruses (IAVs) circulating in humans are mostly related to AIVs, and the possibility that AIVs may mutate and adapt to infect humans cannot be ruled out.⁶ Currently, the main subtypes of influenza A circulating in China are H1N1 and H3N2, both of which originate in birds and have caused pandemics infecting millions of people.7, 8 Since the beginning of the coronavirus disease (COVID-19) pandemic, the number of influenza cases in China has fallen to its lowest level in decades. However, the prevention and control measures executed by China over the past 3 years have prevented the spread of COVID-19 as well as influenza, which has reduced the anti-influenza immunity of the entire population, providing favorable conditions for an epidemic. When the epidemic prevention and control measures implemented by China were changed on December 13, 2022, the number of weekly confirmed cases increased and subsequently decreased rapidly within a few weeks after people gained specific immunity to COVID-19 ( Fig. 1); this can be attributed to the cancellation of large-scale nucleic acid testing. There is no cross-immunity protection against COVID-19 and influenza, and people who have recently been infected with COVID-19 do not exhibit a protective effect against influenza. With the alternation of winter and spring, the influenza epidemic in China peaked in March, and H3N2 and H1N1 IAVs were the main subtypes, with a small number of influenza B cases (Victoria) (Fig. 1). Following the height of COVID-19, citizen behavioral patterns have changed significantly, with more frequent contact resulting in greater susceptibility to influenza. Compared with the epidemic prevention and control period of the previous two years, the percentage of influenza-like illness cases reported by sentinel hospitals in China has increased significantly between December 2022 and March 2023 ( Fig. 2).

Fig. 1.

Weekly positive samples of influenza viruses and confirmed COVID-19 cases in China (updated on April 30th, 2023). Data for positive samples of influenza viruses are from the Chinese National Influenza Center (https://ivdc.chinacdc.cn/cnic) and confirmed COVID-19 cases are from the World Health Organization (https://covid19.who.int).

Fig. 2.

Percentages of influenza-like illness cases in total outpatient cases in southern and northern China between 2020 and 2023 (updated on April 30th, 2023). Data for influenza-like illness cases (%) are from the Chinese National Influenza Center (https://ivdc.chinacdc.cn/cnic).

Currently, it is rare for a human to contract AIV to from another human who contracted it from a bird. But the warning is that once cross-species transmission occurs, human infections can lead to adaptive mutations in viruses that may allow them to spread more easily within species. The industrialization and mixed farming of different animal species, combined with live poultry markets, create an ideal environment for the recombination and interspecific transmission of influenza viruses. Continued human infection with the novel H3N8 virus may drive the virus to acquire a preference for binding to human receptors, a prerequisite for a potential H3N8 virus pandemic.² Although the virus transmission risk is low at this stage and no human-to-human transmission has been detected, we should not take it lightly and still adopt effective prevention and surveillance strategies.

On May 5, 2023, the WHO officially declared that COVID-19 no longer constituted a “public health emergency of international concern.” However, in the post-COVID-19 era, the continued cocirculation of SARS-CoV-2 and influenza viruses is expected to present challenges to healthcare systems globally. We must anticipate and consider a holistic approach to combat this dual threat, which could pose a serious challenge owing to the concurrent burden of both diseases. Strengthening pathogen surveillance for emerging infectious diseases has become an important global public health topic. Local epidemics caused by viral mutations can be expected to occur frequently. In the future, the prevalence of other emerging infectious diseases will pose a public health challenge in China.

Declaration of Competing Interest

None.