P.C.Y. Woo’s research while affiliated with National Chung Hsing University and other places

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Publications (957)


Bats as a mixing vessel for generation of novel coronaviruses: Co-circulation and co-infection of coronaviruses and other viruses
  • Literature Review

March 2025

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9 Reads

Virology

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Susanna.K.P. Lau

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Patrick.C.Y. Woo

Figure 1. Neighbor-Joining tree reconstructed using HBV/B full genome sequences (n = 331) from East Asian countries. The numbers on the branches represent the bootstrap values. Outgroup sequences (genotype C) are marked light blue for outgroup rooting. Countries are specified according to color. Abbreviations: HBV/B: Hepatitis B virus genotype B.
Figure 2. Maximum Likelihood tree reconstructed using HBV/B full genome sequences (n = 331) from East Asian countries. The numbers on the branches represent likelihood ratio test values (in the format of 0.XX). Outgroup sequences (genotype C) are marked light blue for outgroup-rooting. Countries are specified according to color. Abbreviations: HBV/B: Hepatitis B virus genotype B.
Figure 3. The Bayesian maximum clade credibility tree was reconstructed using HBV/B full genome sequences across East Asian countries (n = 150). Posterior probability (in the format of 0.XX) indicates the statistical results of branching. Countries are specified according to color. Abbreviation: HBV/B: Hepatitis B virus genotype B.
Figure 4. HBV/B and HBV/C phylogeography in East Asian countries visualized using Google Earth. Abbreviations: HBV/B: Hepatitis B virus genotype B; HBV/C: Hepatitis B virus genotype C.
Phylodynamics of hepatitis B virus genotype B in East Asia: A population genomics analysis
  • Article
  • Full-text available

January 2025

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2 Reads

Journal of Biological Methods

Background: Hepatitis B virus (HBV) genotype B (HBV/B) is the predominant strain in Taiwan and several East Asian countries. Objective: The aim of this study is to use comprehensive phylogenetic analysis tools to monitor the long-term molecular evolution dynamic of HBV genotype B population in East Asia. Methods: In this study, full genome sequences of HBV with temporal information were extracted from GenBank and analyzed using the Bayesian Markov chain Monte Carlo method to identify best-fitting coalescent models. Results: Bayesian Skygrid analysis revealed a viral effective population (phylodynamic) bottleneck for HBV/B in 2003, a pattern similar to the previously described HBV genotype C (HBV/C). Despite these similarities, the viral dynamics for HBV/B and HBV/C diverged after 2005. HBV/C exhibited a marked decrease in genetic diversity across East Asia, whereas HBV/B maintained stable genetic diversity after 2005. Phylogeographic analysis using Neighbor-Joining and Bayesian maximum clade credibility trees indicated that Taiwan was likely the geographic origin of the most recent common ancestor of HBV/B in East Asia. An early clade spread to Japan and subsequently to the West Coast of the United States of America. Another clade dispersed to China, spread widely across the region, and was reintroduced to Taiwan multiple times. In contrast, HBV/C likely originated in China and spread to Japan, Korea, and Taiwan over several decades. Conclusion: This study highlights the similarities and differences between the viral dynamics and geographical evolutionary pathways between HBV/B and HBV/C.

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Next-generation sequencing for laboratory diagnosis of infectious diseases

December 2024

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4 Reads


Automatic identification of clinically important Aspergillus species by artificial intelligence-based image recognition: proof-of-concept study

November 2024

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47 Reads

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Yueh Liu

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[...]

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Patrick C Y Woo

While morphological examination is the most widely used for Aspergillus identification in clinical laboratories, PCR–sequencing and MALDI–TOF MS are emerging technologies in more financially-competent laboratories. However, mycological expertise, molecular biologists and/or expensive equipment are needed for these. Recently, artificial intelligence (AI), especially image recognition, is being increasingly employed in medicine for fast and automated disease diagnosis. We explored the potential utility of AI in identifying Aspergillus species. In this proof-of-concept study, using 2813, 2814 and 1240 images from four clinically important Aspergillus species for training, validation and testing, respectively; the performances and accuracies of automatic Aspergillus identification using colonial images by three different convolutional neural networks were evaluated. Results demonstrated that ResNet-18 outperformed Inception-v3 and DenseNet-121 and is the best algorithm of choice because it made the fewest misidentifications (n = 8) and possessed the highest testing accuracy (99.35%). Images showing more unique morphological features were more accurately identified. AI-based image recognition using colonial images is a promising technology for Aspergillus identification. Given its short turn-around-time, minimal demand of expertise, low reagent/equipment costs and user-friendliness, it has the potential to serve as a routine laboratory diagnostic tool after the database is further expanded.


Figure 1. Computed tomography (CT) and ultrasonographic scan of Case 1. (A and B) Plain CT scan of the abdomen on day 5 after admission, showing multiple round lesions with hypoattenuation and untidy margin in both lobes of the liver and spleen, with the largest one measuring 32 mm × 16 mm (arrow) in the segment VI of the liver. (C and F) Contrast enhanced CT scan of the abdomen on day 7 after admission, showing peripheral rim enhancement around the low-density lesions in both lobes of the liver in the arterial phase (C and D) and portal venous phase (E and F). (G) Ultrasonographic scan of the liver on day 9 after admission, showing multiple hypoechoic lesions (arrow) in the right lobe of the liver, with the largest one measuring 33 mm × 25 mm. (H) Ultrasonographic scan of the liver on day 48 after admission, showing reduction in size and number of the hypoechoic lesions (arrowhead) in the right lobe of the liver.
Figure 2. Computed tomography (CT) and ultrasonographic scan of Case 2 on day 2 after admission. (A) Contrast enhanced CT scan of the abdomen, showing multiple well-demarcated water-attenuation lesions (arrows) with peripheral transient abnormal perfusion and blurred margins in some of the lesions. (B) Contrast enhanced CT scan of the abdomen, showing the enlarged gall bladder with transient abnormal perfusion (arrowheads) in the adjacent lobe of the liver. (C) Ultrasonographic scan of the liver, showing multiple anechoic unilocular fluid-filled spaces with imperceptible walls and posterior acoustic enhancement, with the largest one measuring 35 mm × 33 mm (arrows) in the caudate lobe of the liver. (D) Ultrasonographic scan of the liver, showing an echogenic focus casting an acoustic shadow (arrowhead) and a large amorphous collection of sludge not casting an acoustic shadow (dotted arrows) within the gallbladder.
Klebsiella pneumoniae liver abscess diagnosed by mNGS
Rapid diagnosis of culture-negative Klebsiella pneumoniae liver abscesses by next-generation sequencing: A case series

November 2024

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11 Reads

Diagnosis of Klebsiella pneumoniae (Kp) pyogenic liver abscesses is usually achieved by imaging and isolation of the bacterium. However, when blood and other cultures were negative, laboratory diagnosis of Kp liver abscess may be challenging. Herein we report two patients with culture-negative Kp liver abscess with atypical presentations diagnosed by metagenomic next-generation sequencing (mNGS). For the first non-diabetic patient, computed tomography examination of the abdomen showed multiple round low-density foci with untidy margin in the liver, which mimicked hydatid cysts; while the second patient presented with acute cholecystitis/cholangitis. mNGS analysis of the blood sample from the first patient revealed 144 sequence reads of Kp; and that of the second revealed 153 sequence reads of Kp as well as other latent or non-pathogenic microorganisms. Both patients responded promptly to antibiotics treatment. mNGS is a useful tool for laboratory diagnosis of culture-negative Kp liver abscess.


Clinical and radiological assessment of the index patient. Panel A: Clinical photo on admission, showing subcutaneous nodules on left chest wall and crusting due to healing herpes zoster. Panel B: Thoracic computerized tomography (CT) on admission, showing multiple patchy infiltrates and consolidation with air bronchograms in both lungs and bilateral pleural effusion. Panel C: Mediastinum window of thoracic CT on admission, showing multiple subcutaneous nodules of low density in the left chest wall (arrow). Panel D: Thoracic CT two weeks after commencement of antifungal therapy, showing resolving lung infiltrates and consolidation, and residual pleural effusion. Panel E: Mediastinum window of thoracic CT two weeks after commencement of antifungal therapy, showing shrinking of the subcutaneous nodules in left chest wall (arrow)
Temporal and geographical distribution of T. marneffei infections in renal transplant recipients. Panel A: Number of reported cases of T. marneffei infections in renal transplant recipients from 1990 to 2023. Panel B: Global distribution of reported cases of T. marneffei infections in renal transplant recipients. The number of patients is depicted in different grades of purple color
Comparison of time taken for diagnosis of T. marneffei infection by mNGS and culture. Panel A: The 4 cases diagnosed by both mNGS and culture. Panel B: The 6 cases diagnosed by mNGS and the 7 cases diagnosed only by culture
Emergence and Rapid Diagnosis of Talaromyces marneffei Infections in Renal Transplant Recipients by Next-Generation Sequencing

October 2024

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15 Reads

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1 Citation

Mycopathologia

In the last few years, next-generation sequencing (NGS) has emerged as a technology for laboratory diagnosis of many culture-negative infections and slow-growing microorganisms. In this study, we describe the use of metagenomic NGS (mNGS) for rapid diagnosis of T. marneffei infection in a 37-year-old renal transplant recipient who presented with chronic pneumonia syndrome. Bronchoalveolar lavage for mNGS was positive for T. marneffei sequence reads. Prolonged incubation of the bronchoalveolar lavage revealed T. marneffei colonies after 6 days of incubation. Analysis of 23 cases of T. marneffei infections in renal transplant recipients from the literature revealed that the number of cases ranged from 1 to 4 cases per five years from 1990 to 2020; but increased rapidly to 9 cases from 2021 to 2023, with 7 of them diagnosed by NGS. Twenty of the 23 cases were from T. marneffei-endemic areas [southern part of mainland China (n = 9); Hong Kong (n = 4); northeastern India (n = 2); Indonesia (n = 1) and Taiwan (n = 4)]. For the 3 patients from non-T. marneffei-endemic areas [United Kingdom (n = 2) and Australia (n = 1)], they had travel histories to China and Vietnam respectively. The time taken for diagnosis by mNGS [median 1 (range 1 to 2) day] was significantly shorter than that for fungal culture [median 6 (range 3 to 15) days] (P = 0.002). mNGS is useful for picking up more cases of T. marneffei infections in renal transplant recipients as well as providing a rapid diagnosis. Talaromycosis is an emerging fungal infection in renal transplant recipients.


Thoracic computed tomography scan of Case 2 and 3 before and after specific antibiotic treatment
Panel A: Case 2, day 9 after admission, showing diffuse interstitial infiltrates and ground-glass nodules in both lungs; Panel B: Case 2, day 40 after admission, showing clearance of infiltrates and nodules; Panel C: Case 3, day 5 after admission, showing infiltrates in the posterior segment of the upper lobe of the right lung; Panel D: Case 3, day 64 after admission, showing clearance infiltrates.
Clinical-radiological assessment of Case 4, 5 and 6
Panel A: eschar on lower back of Case 4; Panel B: eschar on abdominal wall of Case 5; Panel C: eschar on lower back of Case 6; Panel D: color doppler flow imaging for the left leg of Case 6, showing a 2.66 cm × 0.681 cm hypoechoic clot in the intermuscular vein lumen of the left leg (arrow), non-compressibility of the vein, and no spontaneous venous flow in the local intermuscular veins.
Results of blood tests for patients in the present study
Results of mNGS analysis for patients in the present study
Results of rickettsia serology tests for patients in the present study
Usefulness of next-generation sequencing for laboratory diagnosis of rickettsiosis

October 2024

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15 Reads

Rickettsiosis includes a diversity of culture-negative non-specific systemic infections. Laboratory diagnosis of rickettsiosis is often not easy. In this 12-month study, six patients with a variety of rickettsia infections of the spotted fever group, typhus group and scrub typhus were diagnosed directly or indirectly by metagenomic next-generation sequencing (mNGS). The patient with Japanese spotted fever was rapidly made when mNGS analysis of the patient’s blood revealed Rickettsia japonica sequences. For the two patients with Rickettsia felis chest infections, the bacterium was detected in the bronchoalveolar lavage of one case and lung biopsy of the other. Both patients had underlying malignancies, carcinoma of the breast and carcinoma of the lung respectively, and were on chemotherapy with immunosuppressive effect. For the remaining three patients who presented over a period of 13 weeks, all had fever, headache and the typical eschar. They also had increased serum transaminases and responded promptly to doxycycline. However, the Weil-Felix test results of all three patients were negative. Since we considered the three cases typical of rickettsiosis, we submitted their serum samples for mNGS analysis. Results showed that Orientia tsutsugamushi sequences were present in the serum of one case. In view of the positive mNGS results, we repeated the Weil-Felix test for the residual sera of all three patients and it revealed that those of the other two cases showed OX-19 titers of 1:640 and 1:160 respectively, inferring that these two patients probably had rickettsiosis of the typhus group. As for the patient positive for O. tsutsugamushi sequences, we also detected IgM for O. tsutsugamushi in the serum, which double confirmed that it was a case of scrub typhus. mNGS is an important molecular tool and can complement serology for laboratory diagnosis of rickettsiosis.




Antimicrobial activity of ceftazidime-avibactam and ceftolozane-tazobactam against the additional 32 ESBL-producing and 101 CPE strains.
Antimicrobial activity of ceftazidime-avibactam and ceftolozane-tazobactam against the additional 101 CPE strains according to the carbapenemase gene present.
Antibiotic Susceptibility of Aerobic and Facultative Anaerobic Gram-Negative Rods in Hong Kong and Implications on Usefulness of Ceftazidime-Avibactam and Ceftolozane-Tazobactam

August 2024

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33 Reads

Antibiotics

Due to the increasing resistance of aerobic and facultative anaerobic Gram-negative rods, ceftazidime-avibactam and ceftolozane-tazobactam have been launched in the market in the last few years. In this study, we analyzed the susceptibility pattern of the major aerobic and facultative anaerobic Gram-negative rods in Hong Kong for ceftazidime-avibactam, ceftolozane-tazobactam, four other broad-spectrum antibiotics commonly used in Hong Kong and colistin. For 300 isolates collected from January to December 2021, non-ESBL-producing Enterobacterales, ESBL-producing Enterobacterales and Pseudomonas aeruginosa were highly susceptible to ceftazidime-avibactam (all 100%) and ceftolozane-tazobactam (98.7%, 99.7% and 94.3%). For 32 archived ESBL-producing Klebsiella pneumoniae isolates collected between January 2014 and March 2023, all were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam. For 101 archived carbapenemase-producing Enterobacterales, their susceptibilities to ceftazidime-avibactam and ceftolozane-tazobactam varied depending on the type of carbapenemase produced. Both had high activities against OXA-producing strains (97.1% and 76.5%, respectively) but were 100% resistant for NDM-producing and NDM+OXA-producing strains. All KPC-producing strains were susceptible to ceftazidime-avibactam but resistant to ceftolozane-tazobactam. Ceftazidime-avibactam and ceftolozane-tazobactam are good alternatives for the management of infections caused by ESBL-producing Enterobacterales and selective strains of carbapenemase-producing Enterobacterales in Hong Kong.


Citations (69)


... Nineteen studies [18, 19, 21, 23-29, 32, 33, 35-37, 39-41] assessed the performance of qPCR in respiratory tract samples like BALF, ETA, sputum, and others. Five studies [20,22,31,34,38] evaluated BDG in serum or BALF, two studies [17,30] used nested PCR, one study [44] employed ddPCR, and three studies [34,42,43] used mNGS. Nine studies were conducted in France [19, 21-23, 25, 26, 28, 38, 40], four studies in China [34,[42][43][44], and Belgium [19,22], Japan [18,20], Australia [33,41], India [29,37] and Spain [30,39] contributed with two studies each. ...

Reference:

Diagnostic tests performance in detecting Pneumocystis jirovecii: A systematic review and meta-analysis
Rapid Diagnosis of Pneumocystis jirovecii Pneumonia and Respiratory Tract Colonization by Next-Generation Sequencing

Mycopathologia

... Some authors report the key role of bats in development of emergent infections as natural reservoirs for numerous microorganisms (Han et al., 2015;Donnik et al., 2021). Most emergent infections with bats as natural reservoirs are viral, such as SARS, MERS, Ebola hemorrhagic fever, diseases caused by the Nipah virus and Hendra henipavirus, and COVID-19 (Caron et al., 2018;Gazal et al., 2022;Li et al., 2023). Most studies on the bat microbiome concentrate therefore on their virome and individual viruses, while the works on bacteria and fungi inhabiting the microbial communities of these animals are scarce. ...

Bats—The Magnificent Virus Player: SARS, MERS, COVID-19 and Beyond

... Additionally, soluble ACE2 (sACE2) proteins have been explored as antiviral inhibitors ( 22 -27 ), offering the advantages of broadly blocking antibody-escape variants of SARS-CoV-2 such as Delta and Omicron. However, it has been observed that low doses of sACE2 can facilitate SARS-CoV-2 infection ( 28 ), although this finding is still under debate ( 29 , 30 ). An outstanding question is whether soluble ACE2 or ACE2 mimetics can serve as viral receptors when associated with the cell membrane. ...

Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system
  • Citing Article
  • November 2023

Cell

... There are countless therapeutic options for their treatment, and in clinical practice, an empirical regimen of oral or parenteral antimicrobials is followed [93]. Nevertheless, systemic side effects and drug resistance remain considerable limitations in treating respiratory infections [94]. The administration of antimicrobials by the pulmonary route can overcome these challenges. ...

Antimicrobial surveillance: A 20-year history of the SMART approach to addressing global antimicrobial resistance into the future
  • Citing Article
  • October 2023

International Journal of Antimicrobial Agents

... The shift from saprophytic to yeast from further complicates the host response as different antigens are presented by the fungus (42). Recent reports also indicate that human bronchial epithelial cells can act as reservoirs for T. marneffei, with intracellular yeast hiding within these cells, making them immunological privileged sites for the fungus to evade the immunosurveillance activity (43). Additionally, regulating the expression of programmed death-ligand 1 (PD-L1) or CD274 by stellate macrophages (Kupffer cells) is noted as another strategy for T. marneffei to circumvent immune recognition (40). ...

Differential innate immune responses of human macrophages and bronchial epithelial cells against Talaromyces marneffei

... Nocardia kroppenstedtii is known for causing severe invasive infections that can be life-threatening. Since its initial identifcation in 2014, only six cases have been reported in [12,[17][18][19][20] (Table 2). Tis case also marks the frst time that MALDI-TOF has been successfully used in diagnosing Nocardia kroppenstedtii. ...

Rapid diagnosis of fatal Nocardia kroppenstedtii bacteremic pneumonia and empyema thoracis by next-generation sequencing: a case report

... The feline coronavirus (FCoV) belongs to the order Nidovirales, family coronaviridae, and genus Alphacoronavirus-1 [1]. The viral genome consists of a single molecule of single-strand RNA ranging from 29 to 30 kilobases in size. ...

ICTV Virus Taxonomy Profile: Coronaviridae 2023

Journal of General Virology

... Similarly, a previous study reported that the carbapenem resistance among Enterobacterales was rare in Hong Kong. 26 Though K. pneumoniae strains carrying the carbapenemase gene bla KPC-2 , the polymyxin resistance gene mcr-8.1 and tigecycline resistance gene tmexC1-tmexD1-toprJ1 have been isolated. It is worth mentioning that 76 strains (32.7%) carried the ESBL encoding genes and most of them were collected from QMH hospital during 2016-2017. ...

Carbapenem resistance among Gram-negative isolates collected from patients in ICU and non-ICU hospital wards in Hong Kong: SMART 2017-2020
  • Citing Article
  • April 2023

Journal of Global Antimicrobial Resistance

... In the last few years, next-generation sequencing (NGS) has emerged as a technology for laboratory diagnosis of many culture-negative infections [7,8]. We have recently reported its application in confirming the first case of listeria meningitis in a patient with autoantibody PLOS NEGLECTED TROPICAL DISEASES against interferon gamma and a patient with fatal Nocardia kroppenstedtii bacteremic pneumonia and empyema thoracis as well as understanding the spectrum of Q fever, fungal infections, Whipple's disease and culture-negative meningitis and encephalitis [8][9][10][11][12][13]. In this study, we report the usefulness of NGS for the laboratory diagnosis of the relatively less common rickettsiosis as well as re-confirming the diagnosis of scrub typhus and other rickettsia infections with false-negative Weil-Felix test results. ...

Emergence of Tropheryma whipplei detection in respiratory samples by next-generation sequencing: Pathogen or innocent bystander?

Journal of Infection

... Kalidium cuspidatum is one kind of predominant plant in saline-alkaline lands, at the inner drought area in northwest China. During an ongoing research project on the collection of beneficial bacteria from the rhizosphere soil of halophyte Sun et al. 2022;Shang et al. 2022;Feng et al. 2022;Zhang et al. 2020), an IAA-producing strain was isolated from the rhizosphere soil of K. cuspidatum. In this study, we determine its accurate taxonomic position using a polytaxonomic approach including genomic analysis. ...

Ignatzschineria rhizosphaerae sp. nov. Isolated from Rhizosphere Soil of the Halophyte Kalidium cuspidatum
  • Citing Article
  • September 2022

Current Microbiology