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Article: Neutrophil extracellular traps and thrombogenesis in COVID-19 patients.

Yaqinuddin, Ahmed

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences

2021 Volume 26, Page(s) 96

Abstract: COVID-19 has caused significant morbidity and mortality around the world. Recent reports point toward the "cytokine storm" as core of pathogenesis in SAR-CoV-2-induced acute lung injury, acute respiratory distress syndrome (ARDS), coagulopathy, and ... ...

Abstract	COVID-19 has caused significant morbidity and mortality around the world. Recent reports point toward the "cytokine storm" as core of pathogenesis in SAR-CoV-2-induced acute lung injury, acute respiratory distress syndrome (ARDS), coagulopathy, and multiorgan failure. We have presented clinical data here wherein cytokine levels in COVID-19 patients do not match typical cytokine storm seen in ARDS. Interestingly, COVID-19 patients in early disease present with hypoxemia with no significant respiratory dysfunction. In addition, it is reported that hospitalized COVID-19 patients have a high incidence of thrombotic complications, especially involving the pulmonary vasculature. We hypothesized that core to pathogenesis of COVID-19 is the dysregulation of neutrophils, which culminates in excessive release of neutrophil extracellular traps (NETs). Recently, an increasing amount of NETs have been seen in sera of severe COVID-19 patients. We have discussed here mechanisms involved which lead to thrombogenesis and vasculitis because of excessive release of NETs.
Language	English
Publishing date	2021-10-18
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2513029-8
ISSN	1735-7136 ; 1735-1995
ISSN (online)	1735-7136
ISSN	1735-1995
DOI	10.4103/jrms.JRMS_750_20
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities.

Yaqinuddin, Ahmed

Medical hypotheses

2020 Volume 144, Page(s) 110049

Abstract: Of the seven coronaviruses associated with disease in humans, SARS-CoV, MERS-CoV and SARS-CoV-2 cause considerable mortality but also share significant sequence homology, and potentially antigenic epitopes capable of inducing an immune response. The ... ...

Abstract	Of the seven coronaviruses associated with disease in humans, SARS-CoV, MERS-CoV and SARS-CoV-2 cause considerable mortality but also share significant sequence homology, and potentially antigenic epitopes capable of inducing an immune response. The degree of similarity is such that perhaps prior exposure to one virus could confer partial immunity to another. Indeed, data suggests a considerable amount of cross-reactivity and recognition by the hosts immune response between different coronavirus infections. While the ongoing COVID-19 outbreak rapidly overwhelmed medical facilities of particularly Europe and North America, accounting for 78% of global deaths, only 8% of deaths have occurred in Asia where the outbreak originated. Interestingly, Asia and the Middle East have previously experienced multiple rounds of coronavirus infections, perhaps suggesting buildup of acquired immunity to the causative SARS-CoV-2 that underlies COVID-19. This article hypothesizes that a causative factor underlying such low morbidity in these regions is perhaps (at least in part) due to acquired immunity from multiple rounds of coronavirus infections and discusses the mechanisms and recent evidence to support such assertions. Further investigations of such phenomenon would allow us to examine strategies to confer protective immunity, perhaps aiding vaccine development.
MeSH term(s)	Adaptive Immunity ; Antigens/immunology ; Apoptosis ; COVID-19/immunology ; COVID-19/mortality ; Coronavirus Infections/immunology ; Coronavirus Infections/mortality ; Cross Protection ; Cross Reactions ; Disease Outbreaks ; Epitopes, B-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/chemistry ; Humans ; Immune System ; Immunity ; Middle East Respiratory Syndrome Coronavirus ; SARS Virus ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome/immunology ; Severe Acute Respiratory Syndrome/mortality
Chemical Substances	Antigens ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte
Keywords	covid19
Language	English
Publishing date	2020-06-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.110049
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Article: Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities

Yaqinuddin, Ahmed

Med Hypotheses

Abstract	Of the seven coronaviruses associated with disease in humans, SARS-CoV, MERS-CoV and SARS-CoV-2 cause considerable mortality but also share significant sequence homology, and potentially antigenic epitopes capable of inducing an immune response. The degree of similarity is such that perhaps prior exposure to one virus could confer partial immunity to another. Indeed, data suggests a considerable amount of cross-reactivity and recognition by the hosts immune response between different coronavirus infections. While the ongoing COVID-19 outbreak rapidly overwhelmed medical facilities of particularly Europe and North America, accounting for 78% of global deaths, only 8% of deaths have occurred in Asia where the outbreak originated. Interestingly, Asia and the Middle East have previously experienced multiple rounds of coronavirus infections, perhaps suggesting buildup of acquired immunity to the causative SARS-CoV-2 that underlies COVID-19. This article hypothesizes that a causative factor underlying such low morbidity in these regions is perhaps (at least in part) due to acquired immunity from multiple rounds of coronavirus infections and discusses the mechanisms and recent evidence to support such assertions. Further investigations of such phenomenon would allow us to examine strategies to confer protective immunity, perhaps aiding vaccine development.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #642368
Database	COVID19

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Article ; Online: Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities

Yaqinuddin, Ahmed

Medical Hypotheses

2020 Volume 144, Page(s) 110049

Keywords	General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.110049
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.

Noor Eddin, Ahmed / Alfuwais, Mohammed / Noor Eddin, Reena / Alkattan, Khaled / Yaqinuddin, Ahmed

Nutrients

2024 Volume 16, Issue 5

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options ... ...

Abstract	Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients. These changes are often correlated with disease progression and patient outcome, suggesting that GBA modulation may have therapeutic potential. Indeed, targeting the gut microbiota has been shown to be neuroprotective in several animal models, alleviating motor symptoms and mitigating disease progression. However, the translation of these findings to human patients is challenging due to the complexity of ALS pathology and the varying diversity of gut microbiota. This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction. It delineates three main mechanisms by which dysbiosis contributes to ALS pathology: compromised intestinal barrier integrity, metabolic dysfunction, and immune dysregulation. It also examines preclinical evidence on the therapeutic potential of gut-microbiota-modulating agents (categorized as prebiotics, probiotics, and postbiotics) in ALS.
MeSH term(s)	Animals ; Humans ; Amyotrophic Lateral Sclerosis/pathology ; Dysbiosis/etiology ; Gastrointestinal Microbiome/physiology ; Microbiota ; Disease Progression
Language	English
Publishing date	2024-02-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu16050590
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach.

Omer, Mohamed H / Shafqat, Areez / Ahmad, Omar / Nadri, Juzer / AlKattan, Khaled / Yaqinuddin, Ahmed

Journal of clinical medicine

2024 Volume 13, Issue 8

Abstract: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of ... ...

Abstract	Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of proteinuria is the most common method of monitoring treatment response and progression. However, present treatments for LN-corticosteroids and immunosuppressants-target inflammation, not proteinuria. Furthermore, subclinical renal inflammation can persist despite improving proteinuria. Serial kidney biopsies-the gold standard for disease monitoring-are also not feasible due to their inherent risk of complications. Biomarkers that reflect the underlying renal inflammatory process and better predict LN progression and treatment response are urgently needed. Urinary biomarkers are particularly relevant as they can be measured non-invasively and may better reflect the compartmentalized renal response in LN, unlike serum studies that are non-specific to the kidney. The past decade has overseen a boom in applying cutting-edge technologies to dissect the pathogenesis of diseases at the molecular and cellular levels. Using these technologies in LN is beginning to reveal novel disease biomarkers and therapeutic targets for LN, potentially improving patient outcomes if successfully translated to clinical practice.
Language	English
Publishing date	2024-04-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13082339
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19.

Kashir, Junaid / Yaqinuddin, Ahmed

Medical hypotheses

2020 Volume 141, Page(s) 109786

Abstract: Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation ... ...

Abstract	Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 h to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ~100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.
MeSH term(s)	Betacoronavirus/genetics ; Betacoronavirus/isolation & purification ; COVID-19 ; COVID-19 Testing ; COVID-19 Vaccines ; Clinical Laboratory Techniques/economics ; Clinical Laboratory Techniques/methods ; Coronavirus Infections/diagnosis ; Coronavirus Infections/economics ; Coronavirus Infections/virology ; DNA Primers ; Early Diagnosis ; Humans ; Molecular Diagnostic Techniques/economics ; Molecular Diagnostic Techniques/methods ; Nucleic Acid Amplification Techniques/economics ; Nucleic Acid Amplification Techniques/methods ; Pandemics/economics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/economics ; Pneumonia, Viral/virology ; RNA, Viral/analysis ; Real-Time Polymerase Chain Reaction/economics ; SARS-CoV-2 ; Sensitivity and Specificity ; Time Factors
Chemical Substances	COVID-19 Vaccines ; Covid-19 aAPC vaccine ; DNA Primers ; RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-04-25
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.109786
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Article ; Online: Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: Targeting a potential IL-1β/neutrophil extracellular traps feedback loop.

Yaqinuddin, Ahmed / Kashir, Junaid

Medical hypotheses

2020 Volume 143, Page(s) 109906

Abstract: Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5-10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute ... ...

Abstract	Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5-10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, coagulopathy and multiorgan failure is not known. SARS-CoV-2 is an envelope virus with S (spike), M (membrane), N (nucleocapsid) and E (envelop) proteins. In a closely related coronavirus (SARS-CoV), the transmembrane E protein exerts an important role in membrane-ionic transport through viroporins, deletion of which reduced levels of IL-1β and a remarkably reduced lung edema compared to wild type. IL-1β is generated by macrophages upon activation of intracellular NLRP3 (NOD-like, leucine rich repeat domains, and pyrin domain-containing protein 3), part of the functional NLRP3 inflammasome complex that detects pathogenic microorganisms and stressors, while neutrophils are enhanced by increasing levels of IL-1β. Expiring neutrophils undergo "NETosis", producing thread-like extracellular structures termed neutrophil extracellular traps (NETs), which protect against mild infections and microbes. However, uncontrolled NET production can cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), coagulopathy, multiple organ failure, and autoimmune disease. Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19. Considering such assertions, we propose potential drug candidates that could be used to alleviate such pathologies. Considering that recent efforts to ascertain effective treatments of COVID-19 in severe patients has been less than successful, investigating novel avenues of treating this virus are essential.
MeSH term(s)	Acute Lung Injury/drug therapy ; Acute Lung Injury/etiology ; Acute Lung Injury/immunology ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Extracellular Traps/drug effects ; Extracellular Traps/immunology ; Feedback, Physiological ; Humans ; Inflammasomes/immunology ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/immunology ; Models, Biological ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; SARS-CoV-2
Chemical Substances	Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human
Keywords	covid19
Language	English
Publishing date	2020-05-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.109906
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Article ; Online: Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents.

Yaqinuddin, Ahmed / Kashir, Junaid

Medical hypotheses

2020 Volume 140, Page(s) 109777

Abstract: Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate ...

Abstract	Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8
Keywords	covid19
Language	English
Publishing date	2020-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.109777
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Article: Tackling the glial scar in spinal cord regeneration: new discoveries and future directions.

Shafqat, Areez / Albalkhi, Ibrahem / Magableh, Hamzah M / Saleh, Tariq / Alkattan, Khaled / Yaqinuddin, Ahmed

Frontiers in cellular neuroscience

2023 Volume 17, Page(s) 1180825

Abstract: Axonal regeneration and functional recovery are poor after spinal cord injury (SCI), typified by the formation of an injury scar. While this scar was traditionally believed to be primarily responsible for axonal regeneration failure, current knowledge ... ...

Abstract	Axonal regeneration and functional recovery are poor after spinal cord injury (SCI), typified by the formation of an injury scar. While this scar was traditionally believed to be primarily responsible for axonal regeneration failure, current knowledge takes a more holistic approach that considers the intrinsic growth capacity of axons. Targeting the SCI scar has also not reproducibly yielded nearly the same efficacy in animal models compared to these neuron-directed approaches. These results suggest that the major reason behind central nervous system (CNS) regeneration failure is not the injury scar but a failure to stimulate axon growth adequately. These findings raise questions about whether targeting neuroinflammation and glial scarring still constitute viable translational avenues. We provide a comprehensive review of the dual role of neuroinflammation and scarring after SCI and how future research can produce therapeutic strategies targeting the hurdles to axonal regeneration posed by these processes without compromising neuroprotection.
Language	English
Publishing date	2023-05-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1180825
Database	MEDical Literature Analysis and Retrieval System OnLINE

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