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Article ; Online: Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size.

Fong, Carol Ho-Yan / Lu, Lu / Chen, Lin-Lei / Yeung, Man-Lung / Zhang, Anna Jinxia / Zhao, Hanjun / Yuen, Kwok-Yung / To, Kelvin Kai-Wang

iScience

2022 Volume 25, Issue 4, Page(s) 104037

Abstract: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of ... ...

Abstract	The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.
Language	English
Publishing date	2022-03-06
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104037
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effect of vaccine booster, vaccine type, and hybrid immunity on humoral and cellular immunity against SARS-CoV-2 ancestral strain and Omicron variant sublineages BA.2 and BA.5 among older adults with comorbidities

Carol Ho-Yan Fong / Xiaojuan Zhang / Lin-Lei Chen / Rosana Wing-Shan Poon / Brian Pui-Chun Chan / Yan Zhao / Carlos King-Ho Wong / Kwok-Hung Chan / Kwok-Yung Yuen / Ivan Fan-Ngai Hung / Jacqueline Kwan Yuk Yuen / Kelvin Kai-Wang To

EBioMedicine, Vol 88, Iss , Pp 104446- (2023)

a cross sectional studyResearch in context

2023

Abstract: ... Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee ...

Abstract	Summary: Background: Vaccination reduces COVID-19-related hospitalization among older adults. However, how SARS-CoV-2 infection and vaccine regimens affect vaccine-elicited immunity remain unclear. Methods: This is a cross-sectional study recruiting adults aged ≥70 years with comorbidities in Hong Kong. Demographic and clinical information were collected using a questionnaire. Neutralizing antibody (nAb) titers (against ancestral and Omicron strains) and SARS-CoV-2-specific T cell response were analyzed according to infection and vaccination status. Multivariable regression analysis was performed to assess the associations of BNT162b2 and booster doses with higher nAb titers, with adjustment for comorbidities. Findings: In July 2022, 101 patients were recruited, of whom 25 (24%) had previous infection. Overall, the geometric mean titer (GMT) of BA.5 nAb was 2.8-fold lower than that against BA.2 (P < 0.0001). The ancestral strain and BA.2 titers were higher for the 3-4-dose-BNT162 group than the 2-dose-BNT162b2 group. Non-infected individuals in the 3-4-dose-CoronaVac group had a more robust T cell response than the 2-dose-CoronaVac group (P = 0.0181), but there was no significant difference between the 2-dose-BNT162b2 and 3-4-dose-BNT162b groups. Patients who had heterologous CoronaVac-BNT162b2 prime-boost regimen had 3.22-fold higher BA.5 nAb titers than those who were primed/boosted with CoronaVac (P = 0.0207). Patients with hybrid immunity had higher Omicron nAb titers than those with vaccine-only immunity. Multivariable analysis showed that BNT162b2 and booster doses were independently associated with higher ancestral strain nAb titers. Interpretation: Our data support the use of booster doses for older adults with or without prior infection. Non-infected individuals primed with CoronaVac will benefit from heterologous mRNA vaccine booster. Funding: Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service (See acknowledgements for ...
Keywords	COVID-19 ; Vaccination ; Antibody ; T cell ; Booster ; Hybrid immunity ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid.

Zhang, Xiaojuan / Lam, Stephanie Joy-Ann / Ip, Jonathan Daniel / Fong, Carol Ho-Yan / Chu, Allen Wing-Ho / Chan, Wan-Mui / Lai, Yoyo Suet-Yiu / Tsoi, Hoi-Wah / Chan, Brian Pui-Chun / Chen, Lin-Lei / Meng, Xinjie / Yuan, Shuofeng / Zhao, Hanjun / Cheng, Vincent Chi-Chung / Yuen, Jacqueline Kwan Yuk / Yuen, Kwok-Yung / Zhou, Jie / To, Kelvin Kai-Wang

iScience

2024 Volume 27, Issue 5, Page(s) 109706

Abstract: SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. ... ...

Abstract	SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. However, there was no significant difference in virus replication between EG.5.1 and XBB.1.9.1 in human nasal organoids and TMPRSS2/ACE2 over-expressing A549 cells. No significant difference was observed in competitive fitness and cytokine/chemokine response between EG.5.1 and XBB.1.9.1. Both EG.5.1 and XBB.1.9.1 replicated more robustly in the nasal organoid from a younger adult than that from an older adult. Our findings suggest that enhanced immune escape contributes to the dominance of EG.5.1 over earlier sublineages. The combination of population serum susceptibility testing and viral fitness evaluation with nasal organoids may hold promise in risk assessment of upcoming variants. Utilization of serum specimens and nasal organoid derived from older adults provides a targeted risk assessment for this vulnerable population.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109706
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Article ; Online: Effect of vaccine booster, vaccine type, and hybrid immunity on humoral and cellular immunity against SARS-CoV-2 ancestral strain and Omicron variant sublineages BA.2 and BA.5 among older adults with comorbidities: a cross sectional study.

Fong, Carol Ho-Yan / Zhang, Xiaojuan / Chen, Lin-Lei / Poon, Rosana Wing-Shan / Chan, Brian Pui-Chun / Zhao, Yan / Wong, Carlos King-Ho / Chan, Kwok-Hung / Yuen, Kwok-Yung / Hung, Ivan Fan-Ngai / Yuen, Jacqueline Kwan Yuk / To, Kelvin Kai-Wang

EBioMedicine

2023 Volume 88, Page(s) 104446

Abstract: ... Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee ...

Abstract	Background: Vaccination reduces COVID-19-related hospitalization among older adults. However, how SARS-CoV-2 infection and vaccine regimens affect vaccine-elicited immunity remain unclear. Methods: This is a cross-sectional study recruiting adults aged ≥70 years with comorbidities in Hong Kong. Demographic and clinical information were collected using a questionnaire. Neutralizing antibody (nAb) titers (against ancestral and Omicron strains) and SARS-CoV-2-specific T cell response were analyzed according to infection and vaccination status. Multivariable regression analysis was performed to assess the associations of BNT162b2 and booster doses with higher nAb titers, with adjustment for comorbidities. Findings: In July 2022, 101 patients were recruited, of whom 25 (24%) had previous infection. Overall, the geometric mean titer (GMT) of BA.5 nAb was 2.8-fold lower than that against BA.2 (P < 0.0001). The ancestral strain and BA.2 titers were higher for the 3-4-dose-BNT162 group than the 2-dose-BNT162b2 group. Non-infected individuals in the 3-4-dose-CoronaVac group had a more robust T cell response than the 2-dose-CoronaVac group (P = 0.0181), but there was no significant difference between the 2-dose-BNT162b2 and 3-4-dose-BNT162b groups. Patients who had heterologous CoronaVac-BNT162b2 prime-boost regimen had 3.22-fold higher BA.5 nAb titers than those who were primed/boosted with CoronaVac (P = 0.0207). Patients with hybrid immunity had higher Omicron nAb titers than those with vaccine-only immunity. Multivariable analysis showed that BNT162b2 and booster doses were independently associated with higher ancestral strain nAb titers. Interpretation: Our data support the use of booster doses for older adults with or without prior infection. Non-infected individuals primed with CoronaVac will benefit from heterologous mRNA vaccine booster. Funding: Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service (See acknowledgements for full list).
MeSH term(s)	Humans ; Aged ; Cross-Sectional Studies ; SARS-CoV-2 ; BNT162 Vaccine ; COVID-19/epidemiology ; COVID-19/prevention & control ; Vaccines ; Immunity, Cellular ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	sinovac COVID-19 vaccine ; BNT162 Vaccine ; Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-01-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104446
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Humoral and cellular immunity against different SARS-CoV-2 variants in patients with chronic kidney disease.

Yap, Desmond Yat-Hin / Fong, Carol Ho-Yan / Zhang, Xiaojuan / Ip, Jonathan Daniel / Chan, Wan-Mui / Chu, Allen Wing-Ho / Chen, Lin-Lei / Zhao, Yan / Chan, Brian Pui-Chun / Luk, Kristine Shik / Cheng, Vincent Chi-Chung / Chan, Tak-Mao / To, Kelvin Kai-Wang

Scientific reports

2023 Volume 13, Issue 1, Page(s) 19932

Abstract: Chronic kidney disease (CKD) patients are at higher risk of severe COVID-19. Humoral and cellular immunity from prior infection or vaccination are important for protection, but the neutralizing antibody (nAb) response against SARS-CoV-2 variants is ... ...

Abstract	Chronic kidney disease (CKD) patients are at higher risk of severe COVID-19. Humoral and cellular immunity from prior infection or vaccination are important for protection, but the neutralizing antibody (nAb) response against SARS-CoV-2 variants is impaired. We investigated the variant-specific nAb and T cell immunity among CKD patients. Adult CKD patients were recruited between August and October 2022. nAb against the SARS-CoV-2 (ancestral strains and four Omicron sublineages) and T cell response were measured using the live virus neutralization assay and interferon-gamma release assay (IGRA). The correlation between nAb/T-cell response and subsequent infection after recruitment were also determined. Among the 88 recruited patients, 95.5% had prior infection or had completed the primary vaccine series. However, only 77.3% had detectable nAb against at least one SARS-CoV-2 strains, 59.1% tested positive in IGRA, and 52.3% had detectable nAb and tested positive in the IGRA. The nAb geometic mean titers (GMTs) against XBB.1, BA.5 and BA.2.3.20 were significantly lower than those against BA.2 and ancestral strain. Prior SARS-CoV-2 infection was associated with elevated nAb and T cell response. More kidney transplant recipients (KTRs) showed absent nAb and T cell response (36.8% vs. 10.1%), despite a higher prevalence of vaccine booster in this population (94.7% vs. 50.7%). Lower levels of nAb titer and T cell response were significantly associated with subsequent infection. A considerable proportion of CKD patients, especially KTRs, showed absence of humoral and cellular protective immunity against SARS-CoV-2. Strategies to improve immunogenicity in this population are urgently needed.
MeSH term(s)	Adult ; Humans ; SARS-CoV-2 ; COVID-19 ; Immunity, Cellular ; Antibodies, Neutralizing ; Renal Insufficiency, Chronic ; Vaccination ; Vaccines ; Antibodies, Viral ; Immunity, Humoral
Chemical Substances	Antibodies, Neutralizing ; Vaccines ; Antibodies, Viral
Language	English
Publishing date	2023-11-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-47130-8
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Article ; Online: Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size

Carol Ho-Yan Fong / Lu Lu / Lin-Lei Chen / Man-Lung Yeung / Anna Jinxia Zhang / Hanjun Zhao / Kwok-Yung Yuen / Kelvin Kai-Wang To

iScience, Vol 25, Iss 4, Pp 104037- (2022)

2022

Abstract: Summary: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral ... ...

Abstract	Summary: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.
Keywords	Biological sciences ; Immunology ; Microbiology ; Science ; Q
Subject code	612
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Determination of seroprevalence and kinetics of humoral response using mpox virus A29 protein.

Cai, Jian-Piao / Chu, Wing-Ming / Tam, Anthony Raymond / Wang, Kun / Han, Yuting / Chen, Lin-Lei / Zhang, Xiaojuan / Choi, Charlotte Yee-Ki / Cheng, Vincent Chi-Chung / Chan, Kwok-Hung / Chen, Zhiwei / Hung, Ivan Fan-Ngai / Fong, Carol Ho-Yan / To, Kelvin Kai-Wang

Communications medicine

2023 Volume 3, Issue 1, Page(s) 168

Abstract: Background: Mpox virus (MPXV), previously known as monkeypox virus, has spread globally in 2022. An accurate and convenient antibody test is essential for the determination of seroprevalence and for studying immune response after natural infection or ... ...

Abstract	Background: Mpox virus (MPXV), previously known as monkeypox virus, has spread globally in 2022. An accurate and convenient antibody test is essential for the determination of seroprevalence and for studying immune response after natural infection or vaccination. Most seroprevalence or vaccine studies used either live MPXV (or vaccinia virus [VACV]) or inactivated MPXV (or VACV) culture lysate for serological assays, but MPXV culture can only be performed in biosafety level 3 (BSL-3) facilities. Here, we developed and evaluated an enzyme immunoassay (EIA) based on the MPXV A29 surface envelope protein. Methods: We compared the specificity of the MPXV A29, VACV A27, and VACV lysate EIA using serum specimens collected prior to the global spread of MPXV. Next, we performed these EIAs for serum specimens collected from two mpox patients and an MVA-BN vaccine recipient. We also assessed the kinetics of plasmblast and MPXV A29-specific B-cell response. Results: Using sera collected from different age groups in Hong Kong, we found that most individuals, including those born before 1981 who have received the smallpox vaccine, tested negative using the MPXV A29 protein. MPXV A29-specific antibody could be detected in the serum of mpox patients and an MVA-BN recipient. In a mpox patient, the frequency of plasmablast and MPXV A29-specific B cell peaked on day 8 post-symptom onset and gradually decreased. Finally, we demonstrated that antibodies against the A29 protein can be used for immunofluorescence staining of MPXV-infected cells. Conclusions: MPXV A29 protein is suitable for studying the immune response against MPXV infection.
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-023-00403-9
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Article ; Online: A small animal model of chronic hepatitis E infection using immunocompromised rats.

Sridhar, Siddharth / Wu, Shusheng / Situ, Jianwen / Shun, Estie Hon-Kiu / Li, Zhiyu / Zhang, Anna Jin-Xia / Hui, Kyle / Fong, Carol Ho-Yan / Poon, Vincent Kwok-Man / Chew, Nicholas Foo-Siong / Yip, Cyril Chik-Yan / Chan, Wan-Mui / Cai, Jian-Piao / Yuen, Kwok-Yung

JHEP reports : innovation in hepatology

2022 Volume 4, Issue 10, Page(s) 100546

Abstract: Background & aims: HEV variants such as swine genotypes within : Methods: In this animal model infection study, rats were immunosuppressed with a drug combination (prednisolone, tacrolimus, and mycophenolate mofetil) commonly taken by transplant ... ...

Abstract	Background & aims: HEV variants such as swine genotypes within Methods: In this animal model infection study, rats were immunosuppressed with a drug combination (prednisolone, tacrolimus, and mycophenolate mofetil) commonly taken by transplant recipients. Rats were challenged with human- and rat-derived HEV-C1 strains or a human-derived HEV-A strain. Viral load, liver function, liver histology, humoural, and cellular immune responses were monitored. Results: A high-dose (HD) immunosuppressive regimen consistently prolonged human- and rat-derived HEV-C1 infection in rats (up to 12 weeks post infection) compared with transient infections in low-dose (LD) immunosuppressant-treated and immunocompetent (IC) rats. Mean HEV-C1 viral loads in stool, serum, and liver tissue were higher in HD regimen-treated rats than in LD or IC rats ( Conclusions: We developed a scalable immunosuppressed rat model of chronic hepatitis E that closely mimics this infection phenotype in transplant recipients. Lay summary: Convenient small animal models are required for the study of chronic hepatitis E in humans. We developed an animal model of chronic hepatitis E by suppressing immune responses of rats with drugs commonly taken by humans as organ transplant rejection prophylaxis. This model closely mimicked features of chronic hepatitis E in humans.
Language	English
Publishing date	2022-08-10
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-5559
ISSN (online)	2589-5559
DOI	10.1016/j.jhepr.2022.100546
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Article ; Online: SARS-CoV-2 IgG seropositivity after the severe Omicron wave of COVID-19 in Hong Kong.

Poon, Rosana Wing-Shan / Chan, Brian Pui-Chun / Chan, Wan-Mui / Fong, Carol Ho-Yan / Zhang, Xiaojuan / Lu, Lu / Chen, Lin-Lei / Lam, Joy-Yan / Cheng, Vincent Chi-Chung / Wong, Samson S Y / Kok, Kin-Hang / Yuen, Kwok-Yung / To, Kelvin Kai-Wang

Emerging microbes & infections

2022 Volume 11, Issue 1, Page(s) 2116–2119

Abstract: The SARS-CoV-2 Omicron variant has led to a major wave of COVID-19 in Hong Kong between January and May 2022. Here, we used seroprevalence to estimate the combined incidence of vaccination and SARS-CoV-2 infection, including subclinical infection which ... ...

Abstract	The SARS-CoV-2 Omicron variant has led to a major wave of COVID-19 in Hong Kong between January and May 2022. Here, we used seroprevalence to estimate the combined incidence of vaccination and SARS-CoV-2 infection, including subclinical infection which were not diagnosed at the acute stage. The overall seropositive rate of IgG against receptor binding domain (anti-RBD IgG) increased from 52.2% in December 2021 to 89.3% in May 2022. The level of anti-RBD IgG was lowest in the 0-9 and ≥80 year-old age groups in May 2022. The seropositive rate of antibody against ORF8, which reflects the rate of prior infection, was 23.4% in May 2022. Our data suggest that although most individuals were either vaccinated or infected after the fifth wave, children and older adults remain most vulnerable. Public health measures should target these age groups in order to ameliorate the healthcare consequences of upcoming waves.
MeSH term(s)	Aged ; Aged, 80 and over ; Antibodies, Viral ; COVID-19/epidemiology ; Child ; Hong Kong/epidemiology ; Humans ; Immunoglobulin G ; SARS-CoV-2 ; Seroepidemiologic Studies
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2022-08-09
Publishing country	United States
Document type	Letter
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2022.2106899
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Article: Correlation between Commercial Anti-RBD IgG Titer and Neutralization Titer against SARS-CoV-2 Beta Variant.

Poon, Rosana Wing-Shan / Lu, Lu / Fong, Carol Ho-Yan / Ip, Tak-Chuen / Chen, Lin-Lei / Zhang, Ricky Rui-Qi / Yip, Cyril Chik-Yan / Cheng, Vincent Chi-Chung / Chan, Kwok-Hung / Yuen, Kwok-Yung / To, Kelvin Kai-Wang

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 12

Abstract: Objectives: The emergence of SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of vaccines and are associated with a rebound in the number of COVID-19 cases globally. These variants contain mutations at the spike (S) protein ... ...

Abstract	Objectives: The emergence of SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of vaccines and are associated with a rebound in the number of COVID-19 cases globally. These variants contain mutations at the spike (S) protein receptor binding site (RBD), which affect antibody binding. Current commercially available antibody assays were developed before the VOCs emerged. It is unclear whether the levels of these commercially available antibody assays can predict the neutralizing antibody titers against the VOCs. In this study, we sought to determine the correlation between the binding antibody concentration and microneutralization antibody titer against the beta variant. Methods: This study included 58 COVID-19 patients. The concentrations of IgG against the SARS-CoV-2 spike protein RBD and nucleocapsid (N) protein were measured using the Abbott SARS-CoV-2 IgG II Quant assay and the SARS-CoV-2 IgG assay, respectively. The neutralization antibody titer against the wild type lineage A SARS-CoV-2 and against the beta variant (B.1.351) was determined using a conventional live virus neutralization test. Results: The geometric mean MN titer (GMT) against the beta variant was significantly lower than that against the wild type lineage A virus (5.6 vs. 47.3, Conclusions: Currently available commercial antibody assays may not predict the level of neutralizing antibodies against the variants. A new generation of antibody tests specific for variants are required.
Language	English
Publishing date	2021-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11122216
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