Thursday, May 30, 2024

Transboundary & Emerg. Dis: Severe Avian Influenza A H5N1 Infection in a Human with Continuation of SARS-CoV-2 Viral RNAs

When Viruses Collide

#18,090

We've an interesting report today, published in Transboundary & Emerging Diseases, on an apparent co-infection with SARS-COV-2 and HPAI H5N1 clade 2.3.4.4b in a farmer in China. 

While we really can't draw any solid conclusions from a single case, it is important that we try to understand the interactions between COVID and H5N1 before they have an opportunity to act as a viral tag-team against us. 

Previously, we've seen reports of severe co-infections, and sequential infections, with COVID and influenza A, including:

Last year, in  Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study, researchers found that `. . . individuals who had an influenza infection less than 1 year before COVID-19 infection were at an increased risk of experiencing severe illness from the SARS-CoV-2 infection.'

More recently, in SARS-CoV-2 and Influenza Co-Infection: Fair Competition or Sinister Combination? - while they were unable to find conclusive evidence of how influenza co-infection mechanistically modifies disease outcomes of COVID-19 - the authors wrote: `. . . the dramatic increase in SARS-CoV-2 infections and fatalities during influenza epidemic seasons supports the notion that co-infection with both viruses exacerbates lung injury.'

The patient - a 53 year-old underweight female farmer with multiple comorbidities, fell ill with COVID in the days following the disbanding of China's Zero-COVID policies in late 2022.  Her backyard chickens began to die in late January 2023, and a few days later she spiked a fever, and visited a local health Clinic (Feb 2nd).  

Over the next week she would visit a local hospital, and then end up in a tertiary hospital and put on mechanical ventilation.  On day ten of her illness, she would finally be tested, and found positive for by SARS-COV-2 and H5N1 by PCR. 

Ten days later (day 20) she would finally test negative for both viruses.  Her condition improved gradually, and on day 35 she was moved to a general ward. She was discharged on day 44. 

First the link and some excerpts from a much longer report, after which I'll have a bit more.

Severe Avian Influenza A H5N1 Clade 2.3.4.4b Virus Infection in a Human with Continuation of SARS-CoV-2 Viral RNAs
Huiyan Yu,1Ke Jin,2Songning Ding,3Ke Xu,1Xian Qi,1Junjun Wang,3Qigang Dai,1Haodi Huang,1Chaoqi Xu,4Shenjiao Wang,1Fei Deng,1and Jun Li2 et al.

Academic Editor: Nan-hua Chen Published27 May 2024

Abstract

Background.

Since 2020, global attention has heightened towards epidemics caused by avian influenza A H5N1 virus of clade 2.3.4.4b in birds and mammals. This study presents the epidemiological history, clinical manifestations, and prognosis of a unique case infected with avian influenza A H5N1 clade 2.3.4.4b, along with the continuation of SARS-CoV-2 viral RNAs, in Eastern China.

Methods.


We collected and analysed the patient’s clinical, epidemiological, and virological data. Both sputum and bronchoalveolar lavage fluid (BALF) samples were subjected to real-time RT-PCR to test for respiratory pathogens of interests, including SARS-CoV-2 and influenza virus. Influenza virus isolation and propagation were performed on embryonated eggs. Serological tests were used to determine the presence of SARS-CoV-2 antibodies. Phylogenetic analysis was constructed to explore viral evolution and origin of A/H5N1 virus.

Results.

A 53-year-old female farmer with chronic bronchiectasis was hospitalized with severe pneumonia. Real-time RT-PCR revealed the presence of avian influenza A H5N1 and SARS-CoV-2 in BALF and sputum samples. Sequence analyses classified the human isolate as clade 2.3.4.4b of avian influenza A H5N1. The amino acid motif GlnSerGly at residues 226–228 of the haemagglutinin protein indicated avian-like receptor binding preference.
Epidemiological investigation established that the patient had exposure to sick or dead poultry 3 days before illness onset, while no cases of human-to-human H5N1 virus transmission were identified in 31 close contacts.

Conclusion.


We presented that the clade 2.3.4.4b H5N1 avian influenza virus has the potential to cross-infect humans with serious symptoms, especially in individuals already affected by COVID-19. It is indeed crucial to closely monitor the virus’s evolution in both avian populations and humans. Continued research and surveillance efforts are vital to monitor any potential changes in the virus, as well as to inform public health policies and interventions.

          (SNIP)

4. Discussion

(SNIP)
The genetic analysis of the isolated virus from Eastern China showed that it belongs to highly pathogenic avian influenza virus. Like the clade 2.3.4.4b of A H5N1 virus that caused human infection in Europe and America [26, 27], this virus does not currently possess mutations in key sites associated with mammalian adaptation. Therefore, it is still entirely of avian origin and has not yet developed adaptive changes to infect humans. Although the clade 2.3.4.4bA H5N1 virus can occasionally spill over to infection human, it does not currently can easily transmit among people, and its threat to public health is currently low. As the clade 2.3.4.4b of A H5N1 virus continued to spread worldwide and ongoing dynamic evolution with mutations and reassortment, the risk of HPAI virus infection in human might increase. It is necessary to monitor the pandemic potential of HPAI A H5N1 in birds, mammal animal, and human.
Our study has two limitations. First, we did not collect the samples from the sick or dead poultry the patient contacted before her illness onset. Hence, we cannot confirm the exact source of infection of the patient. Second, we cannot determine if post-COVID-19 condition increase the risk of the disease severity of the patient infection with avian A H5N1 virus. The extrapolation of the results warrants more researches in the future.

In conclusion, we report a female farmer with post-COVID-19 condition and multi-comorbidity factor, who had a history of sick or dead poultry exposure, was confirmed infection with the clade 2.3.4.4b avian influenza A H5N1 virus. The pre-existing infection with SARS-CoV-2 did not increase the transmissibility of avian influenza A H5N1 but increase its morbidity and prolong the patient’s hospital stay.
The avian influenza A H5N1 virus bearing clade 2.3.4.4b continues to exist in poultry and has spilled over to human beings. However, there is currently no evidence of adaptive mutations in the virus that would facilitate human-to-human transmission. In the post-COVID-19 pandemic era, sporadic human cases with avian influenza A H5N1 virus are possible to occur, especially among the population who professional or occasional contact with birds or poultry. Active surveillance of individuals following a high-risk exposure to the virus without any PPE protection is strongly recommended.

          (Continue . . .

During the time this patient was hospitalized, it is estimated that somewhere upwards of 2 million Chinese died from COVID alone (see EID Journal: Estimate of COVID-19 Deaths, China, December 2022–February 2023), making it difficult draw much from the severity of this case. 

But since examples of co-infection with  H5N1 and COVID are thankfully rare, any detailed field report on one provides us with important data. 

Interestingly, there is some research to suggest that an existing influenza A infection dramatically inhibits the replication of SARS-CoV-2 viruses in human airway epithelium cells. A process called viral interference. 
Which means taking an antiviral like oseltamivir when co-infected with influenza and COVID might increase SARS-CoV-2 replication, which may limit treatment options for co-infections (see Preprint: Counterintuitive Effect of Antiviral Therapy on Influenza A & SARS-CoV-2 Coinfection Due to Viral Interference). 

There is obviously a lot we still don't know yet about how COVID and other viruses will interact in the human - and even non-human - population.  But since COVID doesn't seem to be going away, and new viruses continue to enter the arena, its a topic very much worth further study.