The Perfect Storm: H5N1 Avian Influenza and COVID-19 Coinfections

In a recent study, published on May 27, 2024, the researchers report a human case with a co-infection with the clade 2.3.4.4b avian influenza A H5N1 virus and COVID-19. This case involved an elderly female farmer with multiple comorbidities who had a history of SARS-CoV-2 infection. This patient tested positive for COVID-19 on December 20, 2022, before her H5N1 infection. This study highlights the importance of surveillance for increased risk of H5N1 virus infection among individuals with post-COVID-19 conditions.

Key Takeaways:

Post-COVID-19 Susceptibility: The case study suggests that individuals who have had COVID-19 may be at increased risk of avian influenza infection due to a weakened immune state.

Ongoing Viral Evolution: The 2.3.4.4b avian influenza strain continues to evolve, highlighting the importance of ongoing surveillance and research.

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The study shows that from mid-December 2022 to early January 2023, China faced an intense wave of SARS-CoV-2 infections. The patient in this case study developed a fever and cough on December 20, 2022, and tested positive for COVID-19. She likely contracted SARS-CoV-2 before her exposure to sick poultry. Positive results for IgG antibodies against SARS-CoV-2 support a previous infection. Her weakened immune state, compounded by low BMI and multiple comorbidities, may have increased her susceptibility to H5N1.

The patient was infected with the clade 2.3.4.4b avian influenza A H5N1 virus, with the case officially reported to the WHO on February 24, 2023. The virus's genes were deposited in the GISAID database on March 3, 2023. Notably, there had been no reported human cases of H5N1 in mainland China from 2015 to 2021, though a case was reported in Guangxi province in October 2022.

The H5N1 clade 2.3.4.4b virus, first identified in 2005 in the Netherlands, has since spread to other parts of Eurasia and America, becoming a primary cause of outbreaks in poultry, wild birds, and dozens of mammals, including cows, cats, goats, and alpaca. The genetic analysis showed the virus belongs to the G10 genotype, which has been found in Russia, Japan, and Southern China since 2021.

Epidemiological investigation suggests the patient may have contracted the virus from her backyard poultry, with whom she had direct contact without personal protective equipment (PPE). Before the onset of her illness, the patient administered antibiotics to sick poultry with her bare hands. “Subsequently, approximately 10 chickens died on January 28, 2023. A total of 31 close contacts were identified, including 29 doctors and nurses who provided medical care to the patient, one patient in the same ward, and the patient’s husband. None of the close contacts developed respiratory symptoms during the 10-day medical observation period. On the last day of the observation period, pharyngeal swabs were collected from close contacts and tested negative for avian influenza type A virus using real-time RT-PCR.

Despite culling and burying the poultry, a lack of samples prevented confirmation of their infection status. Sequence analysis showed the virus isolated from the patient had the highest homology with viruses found in East Asia, indicating a potential cross-species transmission.

The variant that was identified was JS210. This variant does not possess mutations associated with mammalian adaptation, ongoing mutations and reassortment increase the risk of avian influenza viruses infecting humans. Furthermore, no mutations associated with resistance to antiviral drugs such as oseltamivir, zanamivir, and adamantine were detected in the NA and M2 proteins of the JS210 virus. This indicates that the virus remains susceptible to these commonly used influenza treatments. Importantly, the study identifies the following mutations as a something to watch out for. This includes, E627K in PB2, D701N in PB2, and D92E in NS1. These amino acid changes are known to enhance viral polymerase activity in mammalian cells and are linked to increased replication, virulence, and adaptive infection in humans. The absence of these mutations suggests that the JS210 virus currently lacks the enhanced capabilities for human-to-human transmission. Therefore, continuous surveillance of avian influenza virus transmission and evolution is necessary.

In conclusion, the elderly female farmer with post-COVID-19 conditions was confirmed to be infected with the clade 2.3.4.4b avian influenza A H5N1 virus. While her SARS-CoV-2 infection did not increase the transmissibility of H5N1, it did contribute to increased morbidity and a prolonged hospital stay. Although the H5N1 virus continues to spill over to humans, it currently shows no evidence of mutations facilitating human-to-human transmission. However, with increasingly more immune-evasive and suppressive COVID-19 variants, the odds of H5N1 finding individuals currently or recently infected with the latest COVID variants increase. This scenario provides H5N1 with millions of potential human hosts in which it could evolve, potentially leading to human-to-human transmission. Therefore, continuous monitoring and surveillance of both viruses are essential to prevent a possible future pandemic.

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