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Article ; Online: Potential biomarkers for the early prediction of SARS-COV-2 disease outcome.

Mariappan, Vignesh / Manoharan, P S / R, Pajanivel / Shanmugam, Lokesh / Rao, S R / Pillai, Agieshkumar Balakrishna

2021 Volume 158, Page(s) 105057

Abstract: ... biomarker that forecasts the condition of SARS-CoV-2 patients to develop a severe form of the disease ... these may serve as an effective prognostic biomarker in COVID-19 to understand the outcome of the disease. Based ... The current pandemic due to the fast spreading of SARS-CoV-2 infection has caused severe impairment ...

Abstract	The current pandemic due to the fast spreading of SARS-CoV-2 infection has caused severe impairment in health, social, economic, scientific, and medical sectors across the globe. Owing to the not so well understood mechanism of disease pathogenesis in terms of variations in immune responses, there remains obscure why some of the patients who are infected by the novel SARS-CoV-2 develop an unpredictable clinical course that rapidly causes severe and deadly complications/manifestations. Currently, several assays are available for the confirmation of SARS-CoV-2 infection at the point of care. However, none of these assays can predict the severity of the COVID-19 disease. Thus, the identification of a prognostic biomarker that forecasts the condition of SARS-CoV-2 patients to develop a severe form of the disease could enable the clinicians for more efficient patient triage and treatment. In this regard, the present review describes the role of selected biomolecules that are crucially involved in the immune-pathogenesis of SARS-CoV-2 infection such as hyper-immune responsiveness, bradykinin storm and vascular leakage assuming these may serve as an effective prognostic biomarker in COVID-19 to understand the outcome of the disease. Based on the review, we also propose the development of a cost-effective SERS-based prognostic biosensor for the detection and quantification of biomolecules for use as a point-of-care system during a disease outbreak.
MeSH term(s)	Biomarkers ; COVID-19 ; Humans ; Pandemics ; SARS-CoV-2
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-06-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2021.105057
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Article: Potential biomarkers for the early prediction of SARS-COV-2 disease outcome

Mariappan, Vignesh / Manoharan, P.S. / R, Pajanivel / Shanmugam, Lokesh / Rao, S.R. / Pillai, Agieshkumar Balakrishna

Microbial pathogenesis. 2021 Sept., v. 158

2021

Abstract	The current pandemic due to the fast spreading of SARS-CoV-2 infection has caused severe impairment in health, social, economic, scientific, and medical sectors across the globe. Owing to the not so well understood mechanism of disease pathogenesis in terms of variations in immune responses, there remains obscure why some of the patients who are infected by the novel SARS-CoV-2 develop an unpredictable clinical course that rapidly causes severe and deadly complications/manifestations. Currently, several assays are available for the confirmation of SARS-CoV-2 infection at the point of care. However, none of these assays can predict the severity of the COVID-19 disease. Thus, the identification of a prognostic biomarker that forecasts the condition of SARS-CoV-2 patients to develop a severe form of the disease could enable the clinicians for more efficient patient triage and treatment. In this regard, the present review describes the role of selected biomolecules that are crucially involved in the immune-pathogenesis of SARS-CoV-2 infection such as hyper-immune responsiveness, bradykinin storm and vascular leakage assuming these may serve as an effective prognostic biomarker in COVID-19 to understand the outcome of the disease. Based on the review, we also propose the development of a cost-effective SERS-based prognostic biosensor for the detection and quantification of biomolecules for use as a point-of-care system during a disease outbreak.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; biomarkers ; biosensors ; bradykinin ; cost effectiveness ; disease course ; pandemic ; pathogenesis ; patients ; point-of-care systems ; prediction ; storms
Language	English
Dates of publication	2021-09
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2021.105057
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Serum AXL is a potential molecular marker for predicting COVID-19 progression.

You, Jianbin / Huang, Rong / Zhong, Ruifang / Shen, Jing / Huang, Shuhang / Chen, Jinhua / Chen, Falin / Kang, Yanli / Chen, Liangyuan

Frontiers in immunology

2024 Volume 15, Page(s) 1394429

Abstract: ... Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using ... the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased ... COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8-15 ...

Abstract	Background: The severity, symptoms, and outcome of COVID-19 is thought to be closely linked to how the virus enters host cells. This process involves the key roles of angiotensin-converting enzyme 2 (ACE2) and the Tyrosine protein kinase receptor UFO (AXL) receptors. However, there is limited research on the circulating levels of ACE2 and AXL and their implications in COVID-19. Methods: A control group of 71 uninfected individuals was also included in the study. According to the Guidance for Corona Virus Disease 2019 (10th edition), a cohort of 358 COVID-19 patients were categorized into non-severe and severe cases. Serum ACE2/AXL levels in COVID-19 patients were detected by enzyme-linked immunosorbent assay (ELISA) at different time points post-COVID-19 infection, including days 0-7, 8-15, 31-179 and >180 days. Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using an iFlash 3000 Chemiluminescence Immunoassay Analyzer. The receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the biological markers, and the association between laboratory parameters and illness progression were explored. Results: Compared with the uninfected group, the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased. AXL (AUC = 0.774) demonstrated a stronger predictive ability for COVID-19 than ACE2. In the first week after infection, only the level of AXL was statistically different between severe group and non-severe group. After first week, the levels of ACE2 and AXL were different in two groups. Moreover, in severe COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8-15 before declining, whereas serum SARS-COV-2 IgG levels continued to rise, reaching a peak at day 31-180 days before decreasing. In addition, the AXL level continued to decrease and the SARS-COV-2 IgG level continued to increase in the infected group after 180 days compared to the uninfected group. Conclusions: The levels of serum ACE2 and AXL correlate with COVID-19 severity. However, AXL can also provide early warning of clinical deterioration in the first week after infection. AXL appears to be a superior potential molecular marker for predicting COVID-19 progression.
MeSH term(s)	Humans ; Axl Receptor Tyrosine Kinase ; COVID-19/blood ; COVID-19/immunology ; COVID-19/diagnosis ; Receptor Protein-Tyrosine Kinases/blood ; Receptor Protein-Tyrosine Kinases/immunology ; Male ; Proto-Oncogene Proteins/blood ; Female ; Angiotensin-Converting Enzyme 2/blood ; Biomarkers/blood ; Middle Aged ; Disease Progression ; SARS-CoV-2/immunology ; Adult ; Aged ; Antibodies, Viral/blood ; Immunoglobulin G/blood ; Severity of Illness Index ; Immunoglobulin M/blood ; ROC Curve
Chemical Substances	Axl Receptor Tyrosine Kinase ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Proto-Oncogene Proteins ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Biomarkers ; AXL protein, human ; ACE2 protein, human (EC 3.4.17.23) ; Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2024-05-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1394429
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Article ; Online: The role of neurofilament light chain in COVID‑19: A potential prognostic biomarker.

Heidari, Arash / Rezaei, Nima

Acta neurobiologiae experimentalis

2023 Volume 83, Issue 2, Page(s) 111–126

Abstract: ... biomarker could lead to escalated medical care limiting the progression of SARS‑CoV‑2‑induced ... of the disease, efforts have been made to introduce a biomarker to recognize neurological abnormalities early ... coronavirus 2 (SARS‑CoV‑2), and neurological manifestations. Given that the virus‑induced neurological ...

Abstract	Coronavirus disease 2019 (COVID‑19) is an unprecedented global health concern that was declared a pandemic in March 2020. Although primarily recognized by respiratory symptoms, growing evidence suggested the causal relationship between the infection with the disease agent, namely severe acute respiratory coronavirus 2 (SARS‑CoV‑2), and neurological manifestations. Given that the virus‑induced neurological involvement is associated with a poorer prognosis, persistent neurological sequelae, and a more severe form of the disease, efforts have been made to introduce a biomarker to recognize neurological abnormalities early in the course of the disease. Studies indicate a significantly higher concentration of neurofilament light chain (NFL) in cerebrospinal fluid or blood of COVID‑19 patients versus adjusted controls. It has also been reported that COVID‑19 patients suffering from the severe form of the disease had higher NFL levels than patients with mild to moderate forms. Moreover, elevated NFL levels at hospital admission in patients who did not present primarily with neurological expressions could predict the emergence of neurological symptoms during the hospital stay. The early recognition of neurological abnormalities using the NFL biomarker could lead to escalated medical care limiting the progression of SARS‑CoV‑2‑induced central nervous system pathogenesis, resulting in a significant amelioration in disease outcome. Nevertheless, NFL assessment integrated with the evaluation of other neurodegenerative biomarkers and factors indicating disease prognosis could provide a more comprehensive estimate of disease prognosis and the extent of neurological involvement.
MeSH term(s)	Humans ; Intermediate Filaments ; Prognosis ; COVID-19 ; SARS-CoV-2 ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-07-20
Publishing country	Poland
Document type	Journal Article
ZDB-ID	184409-x
ISSN	1689-0035 ; 0065-1400
ISSN (online)	1689-0035
ISSN	0065-1400
DOI	10.55782/ane-2023-011
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Article ; Online: High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19.

Salvio, Andreza Lemos / Fernandes, Renan Amphilophio / Ferreira, Helena França Alcaraz / Duarte, Larissa Araujo / Gutman, Elisa Gouvea / Raposo-Vedovi, Jessica Vasques / Filho, Carlos Henrique Ferreira Ramos / da Costa Nunes Pimentel Coelho, Wagner Luis / Passos, Giselle Fazzioni / Andraus, Maria Emília Cosenza / da Costa Gonçalves, João Paulo / Cavalcanti, Marta Guimarães / Amaro, Marisa Pimentel / Kader, Rafael / de Andrade Medronho, Roberto / Figueiredo, Cláudia Pinto / Amado-Leon, Luciane Almeida / Alves-Leon, Soniza Vieira

Molecular neurobiology

2023 Volume 61, Issue 6, Page(s) 3545–3558

Abstract: ... are early biomarkers of severity and lethality of SARS-COV-2 infection and may be important tools ... to neurological manifestations and severity during and after SARS-CoV-2 infection. The objective of this work was to investigate ... deceased" and "survivor." All subjects were positive for SARS-CoV-2 detection. NfL, total TAU, GFAP, and ...

Abstract	Few studies showed that neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tubulin-associated unit (TAU), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) may be related to neurological manifestations and severity during and after SARS-CoV-2 infection. The objective of this work was to investigate the relationship among nervous system biomarkers (NfL, TAU, GFAP, and UCH-L1), biochemical parameters, and viral loads with heterogeneous outcomes in a cohort of severe COVID-19 patients admitted in Intensive Care Unit (ICU) of a university hospital. For that, 108 subjects were recruited within the first 5 days at ICU. In parallel, 16 mild COVID-19 patients were enrolled. Severe COVID-19 group was divided between "deceased" and "survivor." All subjects were positive for SARS-CoV-2 detection. NfL, total TAU, GFAP, and UCH-L1 quantification in plasma was performed using SIMOA SR-X platform. Of 108 severe patients, 36 (33.33%) presented neurological manifestation and 41 (37.96%) died. All four biomarkers - GFAP, NfL, TAU, and UCH-L1 - were significantly higher among deceased patients in comparison to survivors (p < 0.05). Analyzing biochemical biomarkers, higher Peak Serum Ferritin, D-Dimer Peak, Gamma-glutamyltransferase, and C-Reactive Protein levels were related to death (p < 0.0001). In multivariate analysis, GFAP, NfL, TAU, UCH-L1, and Peak Serum Ferritin levels were correlated to death. Regarding SARS-CoV-2 viral load, no statistical difference was observed for any group. Thus, Ferritin, NFL, GFAP, TAU, and UCH-L1 are early biomarkers of severity and lethality of SARS-COV-2 infection and may be important tools for therapeutic decision-making in the acute phase of disease.
MeSH term(s)	Humans ; Glial Fibrillary Acidic Protein/blood ; tau Proteins/blood ; COVID-19/blood ; COVID-19/mortality ; COVID-19/diagnosis ; Ubiquitin Thiolesterase/blood ; Male ; Biomarkers/blood ; Female ; Neurofilament Proteins/blood ; Middle Aged ; Severity of Illness Index ; Aged ; Adult ; SARS-CoV-2 ; Ferritins/blood ; Viral Load
Chemical Substances	Glial Fibrillary Acidic Protein ; tau Proteins ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; Biomarkers ; Neurofilament Proteins ; neurofilament protein L ; UCHL1 protein, human ; GFAP protein, human ; Ferritins (9007-73-2)
Language	English
Publishing date	2023-11-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03803-z
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Article: Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity.

Schwarz, Yair / Percik, Ruth / Oberman, Bernice / Yaffe, Dana / Zimlichman, Eyal / Tirosh, Amir

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2021 Volume 27, Issue 2, Page(s) 101–109

Abstract: ... tool for disease severity in the early presentation of COVID-19. ... to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 ... Objective: Precise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients ...

Abstract	Objective: Precise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death. Methods: This retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization. Results: Of a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death. Conclusion: FT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.
MeSH term(s)	COVID-19 ; Euthyroid Sick Syndromes ; Humans ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index
Language	English
Publishing date	2021-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.1016/j.eprac.2021.01.001
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Article: Potential targets for preclinical diagnostics of acute kidney injury in covid-19 patients (review of literature).

Maltseva, L D / Lakomova, D Y / Zakharova, N B / Gurova, T S / Morozova, O L

Klinicheskaia laboratornaia diagnostika

2021 Volume 66, Issue 10, Page(s) 586–592

Abstract: ... Disease 2019). Screening of medical literature for selection of AKI preclinical biomarkers was considered ... outcome will be improved due to the identification of high-sensitive specific biomarkers. ... of the biomarkers based on urine proteome and metabolome screening. Perspective ways in the preclinical diagnostics ...

Title translation	Потенциальные мишени для ранней диагностики острого повреждения почек у пациентов с COVID-19 (обзор литературы).
Abstract	An relevance of the topic was defined by the high occurrence, unfavorable prognosis, lack of diagnostic techniques for early stages of acute kidney injury (AKI) disclosed in patients with COVID-19 (Coronavirus Disease 2019). Screening of medical literature for selection of AKI preclinical biomarkers was considered as main aim of this review. More than 200 publications from Russian Science Citation Index (RSCI), Scopus, The Cochrane Library, and MEDLINE were reviewed. Such risk factors as hypoxemia, increased intrathoracic pressure associated with Acute Respiratory Distress Syndrome (ARDS), hypertension (HT) involving endothelial dysfunction, and Diabetes mellitus were considered to be associated with AKI. There were explicated cytopathic and immune-mediated (cytokine-induced) mechanisms of COVID-19 associated AKI pathogenesis. Multiple methodological approaches were defined for detection and identification of the biomarkers based on urine proteome and metabolome screening. Perspective ways in the preclinical diagnostics of AKI such as detection of the markers of injury of the hypoxia-sensitive proximal canaliculi and the ATP metabolites that reflect first stages of the energy metabolism disorder in the epithelium lining canaliculi were identified in this study. The instantaneous and non-invasive investigation of different markers was regarded as possible method of the prognostication. The accuracy of the diagnosis on the initial stages of AKI, substantiate for preventive start of therapy, and make projections on the disease`s outcome will be improved due to the identification of high-sensitive specific biomarkers.
MeSH term(s)	Acute Kidney Injury/diagnosis ; Biomarkers ; COVID-19 ; Humans ; Prognosis ; SARS-CoV-2
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-10-19
Publishing country	Russia (Federation)
Document type	Journal Article ; Review
ZDB-ID	1155086-7
ISSN	0869-2084
ISSN	0869-2084
DOI	10.51620/0869-2084-2021-66-10-586-592
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Article ; Online: Potential biomarkers for the early prediction of SARS-COV-2 disease outcome.

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Article: Potential biomarkers for the early prediction of SARS-COV-2 disease outcome

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Article ; Online: Serum AXL is a potential molecular marker for predicting COVID-19 progression.

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Article ; Online: The role of neurofilament light chain in COVID‑19: A potential prognostic biomarker.

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Article ; Online: High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19.

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Article: Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity.

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Article: Potential targets for preclinical diagnostics of acute kidney injury in covid-19 patients (review of literature).

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