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Phylogenetic and mutational
analysis of H10N3 avian influenza
A virus in China: potential threats
to human health
Jingyi Dai
1
†
, Jun Zhao
2
†
, Jiawei Xia
1
†
, Pei Zhang
1
,
Yadi Ding
1
, Qiujing Li
1
, Min Hou
3
, Xianhui Xiong
3
,
Qianqi Jian
3
, Yanyan Liu
3
*and Guiming Liu
1
*
1
Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease
Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China,
2
School of Public Health, Hubei
University of Medicine, Shiyan, China,
3
Department of Microbiological Laboratory, Kunming City
Center for Disease Control and Prevention, Kunming, China
In recent years, the avian influenza virus has emerged as a significant threat to
both human and public health. This study focuses on a patient infected with the
H10N3 subtype of avian influenza virus, admitted to the Third People’s Hospital of
Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase
chainreaction(PCR)analysiswereconductedonthepatient’ssputum,
confirming the H10N3 infection. The patient presented severe pneumonia
symptoms such as fever, expectoration, chest tightness, shortness of breath,
and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase
(NA) genes of the virus showed that the virus was most closely related to a case of
human infection with the H10N3 subtype of avian influenza virus found in
Zhejiang Province, China. Analysis of amino acid mutation sites identified four
mutations potentially hazardous to human health. Consequently, this
underscores the importance of continuous and vigilant monitoring of the
dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing
advanced genomic surveillance techniques.
KEYWORDS
H10N3, avian influenza A virus, human infection, phylogeny analysis, mutation
Introduction
With the continuous advancement of urbanization and rural development, the
frequency and scope of contact between humans and animals are constantly expanding
(Schell et al., 2021). In cities, people have close contact with poultry and pets, while in rural
areas, farmers and breeders deal directly with poultry and livestock. This kind of contact is
not limited to daily life, but also includes activities such as poultry raising, breeding,
slaughtering, and other activities, providing opportunities for the spread of pathogens
Frontiers in Cellular and Infection Microbiology frontiersin.org01
OPEN ACCESS
EDITED BY
Li Ang,
First Affiliated Hospital of Zhengzhou
University, China
REVIEWED BY
Yaoqiang Shi,
The First People’s Hospital of Yunnan
Province, China
Chao Li,
Chinese Academy of Sciences (CAS), China
*CORRESPONDENCE
Guiming Liu
liuguimingkm@163.com
Yanyan Liu
liuyuxiu07@163.com
†
These authors have contributed
equally to this work and share
first authorship
RECEIVED 16 May 2024
ACCEPTED 07 June 2024
PUBLISHED 24 June 2024
CITATION
Dai J, Zhao J, Xia J, Zhang P, Ding Y, Li Q,
Hou M, Xiong X, Jian Q, Liu Y and Liu G
(2024) Phylogenetic and mutational analysis
of H10N3 avian influenza A virus in China:
potential threats to human health.
Front. Cell. Infect. Microbiol. 14:1433661.
doi: 10.3389/fcimb.2024.1433661
COPYRIGHT
© 2024 Dai, Zhao, Xia, Zhang, Ding, Li, Hou,
Xiong,Jian,LiuandLiu.Thisisanopen-access
article distributed under the terms of the
Creative Commons Attribution License (CC BY).
The use, distribution or reproduction in other
forums is permitted, provided the original
author(s) and the copyright owner(s) are
credited and that the original publication in
this journal is cited, in accordance with
accepted academic practice. No use,
distribution or reproduction is permitted
which does not comply with these terms.
TYPE Original Research
PUBLISHED 24 June 2024
DOI 10.3389/fcimb.2024.1433661
(Tobin et al., 2015;Moyen et al., 2021). Moreover, increased global
trade and travel have intensified the risk of cross-border disease
transmission (Shah et al., 2019). The international trade of animals
and their products facilitates the rapid spread of pathogens
worldwide. Simultaneously, human transnational travel creates
favorable conditions for pathogen dissemination. The occurrence
of a single case can rapidly attract global attention and vigilance. In
this era of interconnectedness and swift information dissemination,
avian influenza, as a significant zoonotic viral infectious disease, has
garnered considerable concern due to its potential transmission
risks and hazards. Consequently, enhancing surveillance,
prevention, and control measures for zoonotic diseases like avian
influenza has emerged as a crucial global public health priority.
Avian influenza virus is a type of RNA virus, classified under the
genus Influenza A virus of the family Orthomyxoviridae, and is
categorized into types A, B, C, and D (Hu et al., 2018). Among
these, avian influenza A virus is particularly concerning for human
health, as it can lead to severe illness and even fatalities. Avian
influenza virus is polymorphic, with a spherical diameter ranging
from 80 to 120 nm and possessing an envelope. Its genome consists
of segmented single-stranded negative-sense RNA, making it highly
variable (Spackman, 2008). Based on the antigenicity of its
hemagglutinin (HA) and neuraminidase (NA) proteins on the
outer membrane, it is currently classified into 18 H subtypes (H1-
H18) and 11 N subtypes (N1-N11) (Li et al., 2021). Human
transmission of avian influenza viruses usually occurs through
contact with infected poultry or their excreta, secretions, etc.,
particularly in settings such as poultry farming, slaughtering, and
handling, where the risks are heightened (Wong and Yuen, 2006).
Individuals infected with avian influenza virus may display a range
of symptoms, with severity varying among cases (Horman et al.,
2018). Common symptoms include fever, cough, runny nose,
headache, muscle and joint pain, fatigue, breathing difficulties,
chest tightness, respiratory failure, nausea, vomiting, diarrhea, etc.
Infection with this virus can lead to severe complications like
pneumonia and acute respiratory distress syndrome (ARDS),
especially in individuals with underlying health conditions or
weakened immune systems. Therefore, prompt medical attention
is essential when experiencing such symptoms, especially if severe
manifestations like breathing difficulties arise. To date, confirmed
subtypes of avian influenza A viruses that have infected humans
include H6N1, H9N2, H10N8, H5N6, H7N4, H10N3, and H5N8,
etc (Yang et al., 2022). Patients infected with H5N1, in particular,
often experience severe illness with a high mortality rate.
Currently, avian influenza virus infection cannot be diagnosed
based on clinical manifestations alone; instead, laboratory testing is
required (Geyer et al., 2022). Commonly used laboratory testing
methods include serological diagnostic methods such as
hemagglutination and hemagglutination inhibition tests,
neuraminidase inhibition test, agarose diffusion test, and enzyme-
linked immunosorbent assay. Additionally, molecular biology
diagnostic technologies such as reverse transcription PCR (RT-
PCR), fluorescent RT-PCR, and Next Generation Sequencing
(NGS) are employed. NGS technology, in particular, provides a
powerful tool for the detection and research of avian influenza
viruses (Soda et al., 2023). It allows high-throughput and deep
sequencing of viral genomes, providing detailed genomic
information, including the virus’s full genome sequence,
mutations, recombination events and gene expression levels
(Quer et al., 2022). This technology not only enables highly
sensitive and specific detection, but also aids researchers in
understanding virus evolution, transmission, and host interactions.
In recent years, human infection with avian influenza virus has
been frequently reported around the world, especially involving
subtypes H5, H7, and other (Gao, 2018;Liang, 2023;Szablewski
et al., 2023). Among these, human infections with H10 avian
influenza A virus have been reported globally, including subtypes
H10N7, H10N8, and H10N3 (Arzey et al., 2012;Chen et al., 2014).
The H10N3 subtype of avian influenza A virus has been circulating
among waterfowl and poultry in East and South Asia for decades,
with rare instances of human infection (Wisedchanwet et al., 2011).
The first recorded human cases of Avian-Origin Influenza A
(H10N3) virus occurred in Jiangsu, China, in April 2021 (Qi
et al., 2022), followed by a second case reported in Zhejiang in
June 2022 (Zhang et al., 2023).
In this study, we utilized metagenomic NGS (mNGS) and
nanopore metagenomic sequencing to document the first
recorded instance of human infection with avian influenza A
virus H10N3 in Yunnan Province. This case marks the
occurrence of H10N3 human infection in China. To elucidate the
virus’s origin, we conducted a comprehensive epidemiological
investigation, performed phylogenetic analysis, and aligned the
virus’sentiregenomesequencewith homologous sequences.
Additionally, to evaluate the virus’s adaptability and pathogenicity
in human hosts, we analyzed the amino acid mutation sites of three
H10N3 subtype AIV infections among humans.
Materials and methods
Data collection
On March 6, 2024 the patient went to Kunming Third People’s
Hospital for treatment due to persistent fever for many days. The
diagnosis revealed severe pneumonia, type I respiratory failure, and
infection with avian influenza A virus. After the diagnosis of avian
influenza A virus infection, the patient underwent investigation
through questionnaires, which included demographic information,
poultry contact history, underlying health conditions, and other
relevant data.
Genomic analysis and genome assembly
Multiple amplification products were obtained using influenza
A virus genotyping gene targeted amplification kit (BaiyiTech,
Hangzhou). The amplified products were purified using ampure
XP beads nucleic acid magnetic bead Purification Kit (Beckman,
USA) and the library was constructed. The library was constructed
by ligation method with the kit sqk-nbd114.24 (Nanopore, UK).
After the library was constructed, it was added to the flo-min 114
sequencing chip (Nanopore, UK), and high-throughput sequencing
Dai et al. 10.3389/fcimb.2024.1433661
Frontiers in Cellular and Infection Microbiology frontiersin.org02
was performed on the gridion X5 third-generation sequencer. All
experimental procedures were meticulously performed in strict
accordance with the instructions provided by the respective kits
and the requirements for the nanopore third-generation high-
throughput sequencing.
Phylogenetic analysis
The nucleotide sequences obtained were analyzed in the
Genbank and GISAID databases (www.gisaid.org)using
Nucleotide Basic Local Alignment Search Tool (BLAST) software
of NCBI to initially determine the virus subtypes. Similar HA and
NA nucleotide sequences were downloaded for phylogenetic
analysis. The nucleotide and amino acid sequences were aligned
using MAFFT (v7.310), and the phylogenetic trees was constructed
based on the neighbor-joining method using MEGA-X.
Ethics statement
The patient and his family members signed consent forms
approving the investigation, sample collection and its publication.
The procedures were in accordance with the Helsinki declaration of
1975, as revised in 1983. This study was approved by the Medical
Ethics Committee at Kunming hird People’sHospital(No.
KSLL20230711009) and adhered to the guidelines established in
the Declaration of Helsinki. To protect patients’personal
information, including names and ID numbers, it was encrypted
before use.
Results
A previously healthy 51-year-old male experienced recurrent
fever for a week, reaching a maximum temperature of 39°C,
accompanied by symptoms of cough, expectoration, chest
tightness, and shortness of breath. Despite seeking medical
attention at the local community health service center, his
symptoms did not significantly improve. Consequently, he was
transferred to the Department of Respiratory and Critical Care
Medicine at the Third People’s Hospital of Kunming City in
Yunnan Province, Southwest China, on March 6, 2024.
Upon admission (7 days after the onset of illness), the patient
presented with a temperature of 39℃, a pulse rate of 110 beats per
minute, a respiratory rate of 28 breaths per minute, oxygen
saturation of 78%, and blood pressure measuring 105/70 mmHg
(Table 1). Laboratory tests revealed a low white blood cell count,
elevated neutrophil percentage, decreased platelet count, and
elevated levels of infectious markers. Additionally, a throat swab
specimen tested positive for influenza A virus nucleic acid by PCR
(Table 2). Chest computed tomography (CT) revealed multiple
patchy and increased density shadows in both lungs, characterized
by unclear boundaries and uneven density (Figure 1). The initial
diagnosis upon admission included severe pneumonia, type I
respiratory failure, and influenza attributed to influenza A virus.
The patient was administered oseltamivir (150mg, twice daily)
and methylprednisolone (80mg, once daily) and corresponding
antibiotics for treatment. Subsequent sputum culture results
revealed infection with Candida albicans and Staphylococcus
epidermidis and Acinetobacter joni and Carbapenem-resistant
Enterobacter cloacae, prompting the administration of appropriate
antibiotics (Table 1). The patient’s fever subsided on March 17th
(18 days after illness onset), and on March 19th (20 days after illness
onset), the nucleic acid test for influenza A virus returned negative
results for the first time. Subsequent test results on March 21st (22
days after illness onset) indicated normalization of the patient’s
white blood cell count, along with a decrease or return to normal
levels of infection markers. However, the patient exhibited
prolonged prothrombin time. Chest computed tomography scans
showed a reduction in lesions compared to previous scans
(Figure 1). The lung lesions were noticeably absorbed, and there
was no chest tightness or dyspnea. The patient was discharged on
April 17th, and home oxygen therapy was recommended.
Although the nucleic acid detection of influenza A virus
confirmed the patient’s infection with influenza A virus, it could
TABLE 1 Patient’s characteristics and clinical symptoms.
Characteristic/
Symptom
Value
Age (years) 51
Sex Male
Date of illness onset 29 Feb 2024
Date of admission 6 Mar 2024
Date of discharge 17 Apr 2024
Signs or symptoms
Fever Yes
Body temperature
(°C)
39.0
Cough Yes
Sputum production Yes
Dizzy Yes
Weakness Yes
Chest tightness Yes
Bacterial culture Staphylococcus epidermidis, Acinetobacter joni,
Carbapenem-resistant Enterobacter cloacae
Fungi culture Candida albicans
Glucocorticoid
therapy
Yes
Antibiotic therapy Meropenem, omacycline, voriconazole,
levofloxacin, amikacin
Antiviral therapy Oseltamivir
Anticoagulant
therapy
Low molecular weight heparin calcium
Oxygen therapy Noninvasive ventilator positive pressure ventilation
Dai et al. 10.3389/fcimb.2024.1433661
Frontiers in Cellular and Infection Microbiology frontiersin.org03
not determine the specific subtype. A sputum sample collected from
the patient on March 8 was confirmed as H10N3 subtype by mNGS
and PCR in the Third People’s Hospital of Kunming City and the
Kunming City Center for Disease Control and Prevention (CDC).
However, epidemiological investigations revealed that the patient
had a history of raising various birds, including chickens, ducks,
geese, pigeons, peacocks, and ostriches. Notably, more than 20
chickens and geese died in the week preceding the onset of his
illness, and he had a history of slaughtering these birds. However,
the virus has not been detected in the environment or in poultry
carcasses. No avian influenza A virus infection was detected in his
close contacts.
To obtain the complete genome sequence of the virus and
clarify its molecular characteristics, the Kunming City CDC
conducted nanopore sequencing (Nanopore, GridION X5) on the
samples, resulting in the acquisition of the whole genome
information of the samples (GISAID#EPIISL19067870), named
A/Yunnan/A/2024(H10N3). Online analysis using BLASTN
software on the GISAID website revealed that all eight gene
segments of the H10N3 virus strain in our case originated from
Eurasian avian influenza viruses. Analysis of the evolutionary trees
of the Haemagglutinin (HA) and neuraminidase (NA) genes
suggested that the patient’s strain is a cross-species infection of
the H10N3 virus, which has been prevalent in poultry in China in
recent years (Figure 2). Homologous comparison in GenBank with
BLAST revealed a high similarity between Yunnan strain’s HA gene
(98.64%) and NA gene (99.43%) with A/Zhejiang/1412/2022
(H10N3) virus (Table 3). Further analysis of amino acid mutation
sites revealed a mutation at the 226th amino acid residue in the
receptor binding site of the HA protein, where the amino acid
changed from Q to L. Additionally, key mutations were identified,
including D701N of PB2 protein, S409N of PA protein, and S31N of
M2 protein (Table 4).
TABLE 2 Laboratory Test Results.
Indicators
Day 7
(6
Mar)
Day 22
(21
Mar)
Normal
range
White Blood Cell (×10
9
cells/L) 2.12 8.58 3.50–9.50
Neutrophil (×10
9
cells/L) 1.80 7.19 1.80–6.30
Neutrophil percentage (%) 84.90 83.90 40.00–75.00
Lymphocyte (×10
9
cells/L) 0.26 0.74 1.10–3.20
Lymphocyte percentage (%) 12.30 8.60 20.00–50.00
Blood platelet (×10
9
cells/L) 79 223 125–350
Prothrombin time (s) 15.9 16.6 14.0–16.0
Hypersensitive C-reactive protein
(mg/L) 249.41 21.93 0.00–6.00
Lnterleukin-6 (pg/mL) 78.99 8.26 0.00–7.00
Procalcitonin (ng/mL) 14.040 0.248 <0.500
pO
2
(mmHg) 32.00 68.40 80.00–100.00
pCO
2
(mmHg) 32.00 52.10 35.00–45.00
Nucleic acid testing for influenza
A virus Positive Negative Negative
FIGURE 1
Computed tomography of lung. (A, B) Results on March 6, 2024 showed that multiple patchy and patchy increased density shadows were seen in
both lungs, with unclear boundary and uneven density; (C, D) Results on March 23, 2024 showed a reduction in lesions compared to previous scans.
Dai et al. 10.3389/fcimb.2024.1433661
Frontiers in Cellular and Infection Microbiology frontiersin.org04
Discussion
Avian influenza virus is typically known for its strong
host species preference and limited transmission to other species
(Kim et al., 2021). However, due to the 8-segment nature of the viral
genome and the RNA error replication mechanism, frequent
recombination and mutation of the virus can occur, potentially
enabling it to survive and spread in other species (Kim et al., 2021).
As a result, various strains of avian influenza viruses have been
identified in marine mammals, terrestrial poultry, horses, dogs,
pigs, and notably, humans (Lloren et al., 2017;Kim et al., 2021;
Kok et al., 2023).
The patient in Yunnan not only exhibited infection with the
H10N3 subtype of influenza A virus but also presented with a mixed
infection involving drug-resistance bacteria and fungi, making the
condition complex. It’s worth noting that severe pneumonia
patients infected with avian influenza often experience concurrent
or secondary bacterial and fungal infections (Chow et al., 2019).
Therefore, it is recommended to conduct repeated sputum culture,
respiratory tract aspirate culture, or mNGS detection in clinical
settings to identify the types of bacteria or fungi present, as well as
their susceptibility or resistance patterns. This approach enables
clinicians to make informed decisions regarding antibiotic selection
and guide appropriate clinical treatment strategies.
The clinical manifestations of avian influenza A virus infection
vary depending on the virus subtypes involved. For instance,
infection with H5N1 and H7N9 subtypes can lead to severe
pneumonia and related complications in patients. Conversely,
certain subtypes such as H7 and H9 may only induce
conjunctivitis or mild respiratory symptoms (Liu et al., 2013).
It’s important for healthcare providers to be aware of these
differences in clinical presentation when diagnosing and
managing cases of avian influenza virus infection. As of now,
only two cases of human infection with the H10N3 subtype have
been reported. The symptoms observed in the patient infected
with H10N3 in this case closely resemble those documented in
the two previously known cases of H10N3 infection. Notably,
all cases resulted in severe pneumonia in the affected patients
(Qi et al., 2022;Zhang et al., 2023).
However, the molecular features of these cases are different, and
our case has some different mutations. The Q226L mutation makes
the virus more adept at binding to human a-2,6-sialic acid
receptors, significantly increasing the likelihood of human
infection (Shi et al., 2014). The mutation D701N in the PB2
protein has been shown to enhance the replication activity of
avian influenza RNA polymerase within the human body.
This mutation also increases the adaptability and pathogenicity
of the virus to the human host, potentially serving as a crucial
factor in avian influenza viruses crossing the host species barrier
(Li et al., 2005). The presence of the S409N mutation in the PA
protein suggests the potential for infectivity in humans and may
contribute to increased pathogenicity of this particular virus strain
(Finkelstein et al., 2007). The S31N mutation in the M2 protein has
been associated with resistance to adamantanes, a class of antiviral
drugs (Pielak et al., 2009). This mutations in the protein of
the Yunnan H10N3 virus strain underscores the potential for
increased threat posed by H10N3 in humans. Therefore, it is
imperative to closely monitor the dynamics of this subtype.
The case of human infection with H10N3 avian influenza A
virus highlighted in this study involved close contact with live birds,
particularly through the handling and slaughtering of dead birds.
Although there is no direct evidence, it is likely that this exposure
B
A
FIGURE 2
Phylogenetic trees of H10N3 strains based on nucleotide sequence.
(A) Phylogenetic tree of HA; (B) Phylogenetic tree of NA. The
Phylogenetic trees were downloaded from the GISAID database
(https://gisaid.org) using the neighbor-joining method in MEGA X.
The diamond indicates the H10N3 strain in this study, and the
octagon indicates the H10N3 strain from the first case in Jiangsu.
Dai et al. 10.3389/fcimb.2024.1433661
Frontiers in Cellular and Infection Microbiology frontiersin.org05
eventually resulted in the patient contracting avian influenza and
experiencing severe illness. This underscores the importance of
paying special attention to instances of unexpected bird deaths
and promptly reporting such cases. Moreover, it emphasizes the
necessity of establishing a comprehensive avian influenza
surveillance system, not only within Yunnan but also globally,
to continuously and vigilantly monitor the H10N3 virus strain
and its potential impact on human health.
TABLE 3 Sequence similarity comparison, A/Yunnan/A/2024(H10N3) compared with A/Zhejiang/1412/2022(H10N3) (ZJ1412) and A/Jiangsu/428/2021
(H10N3) (JS428).
Description Query cover Per.Ident ACC.LEN Description Query cover Per.Ident ACC.LEN
PB2 NP
ZJ1412 97% 99.12% 2280 ZJ1412 96% 99.47% 1497
JS428 99% 96.67% 2280 JS428 100% 96.19% 1497
PB1 NA
ZJ1412 98% 99.65% 2274 ZJ1412 98% 99.43% 1410
JS428 99% 95.78% 2274 JS428 100% 98.01% 1410
PA MP
ZJ1412 97% 99.44% 2151 ZJ1412 95% 99.49% 982
JS428 96% 97.21% 2151 JS428 95% 97.56% 982
HA NS
ZJ1412 99% 98.64% 1686 ZJ1412 97% 99.39% 838
JS428 100% 97.27% 1686 JS428 94% 96.66% 838
TABLE 4 Mutations in A/Yunnan/A/2024(H10N3) and JS428 and ZJ1412, by gene.
Biological function Mutation Yunnan
/A
Jiangsu
/428
Zhejiang
/1412
HA Receptor binding sites Q226L L Q Q
G228S G S G
R229I R I R
Cleavage site PEIIQGR↓G PEIIQGR↓G PEIIQGR↓G
NA Antiviral resistance E119V E E E
Q136K Q Q Q
I222M I I I
R292K R R R
R371K R R R
PB2 Mammalian adaptation Q591K Q K Q
E627K E E E
D701N N D N
PB1 Increased transmission in ferret I368V V V V
PA Host signature V100A V V V
S409N N N N
M2 Antiviral resistance S31N N N N
NS1 Increased virulence in mice D92E D D D
P42S P S S
Dai et al. 10.3389/fcimb.2024.1433661
Frontiers in Cellular and Infection Microbiology frontiersin.org06
Data availability statement
The datasets presented in this study can be found in online
repositories. The names of the repository/repositories and accession
number(s) can be found in the article/supplementary material.
Ethics statement
The studies involving humans were approved by Medical Ethics
Committee at Kunming Third People’s Hospital. The studies were
conducted in accordance with the local legislation and institutional
requirements. The human samples used in this study were acquired
from a by- product of routine care or industry. Written informed
consent for participation was not required from the participants or
the participants’legal guardians/next of kin in accordance with the
national legislation and institutional requirements. Written informed
consent was obtained from the individual(s) for the publication of
any potentially identifiable images or data included in this article.
Author contributions
JD: Conceptualization, Data curation, Supervision, Writing –
original draft, Writing –review & editing. JZ: Conceptualization,
Formal analysis, Software, Supervision, Writing –original draft,
Writing –review & editing. JX: Conceptualization, Resources,
Supervision, Writing –original draft, Writing –review & editing.
PZ: Data curation, Formal analysis, Methodology, Writing –review &
editing. YD: Data curation, Resources, Software, Visualization,
Writing –review & editing. QL: Conceptualization, Data curation,
Formal analysis, Methodology, Project administration, Writing –
review & editing. MH: Investigation, Methodology, Project
administration, Supervision, Writing –review & editing. XX:
Investigation, Methodology, Resources, Writing –review & editing.
QJ: Formal analysis, Investigation, Methodology, Writing –review &
editing. YL: Conceptualization, Methodology, Supervision, Writing –
original draft, Writing –review & editing. GL: Conceptualization,
Supervision, Writing –original draft, Writing –review & editing.
Funding
The author(s) declare financial support was received for the
research, authorship, and/or publication of this article. This
research was supported by Kunming Science and Technology
Bureau (2023-1-NS-007), Kunming Health Commission,
Kunming infectious disease precise diagnosis and treatment
center 2023-SW(JI)-28. This research was also supported by “The
Project of Health Science and Technology Talents Ten Hundred
Thousand’in Kunming”2021-SW(DAITOU)-06.
Acknowledgments
The authors thank the study subject and collaborating clinicians
for their participation and contribution to the work.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
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