Role of Coagulation Profile in Predicting Disease Severity Among Patients of COVID-19

The Coronavirus Disease-2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed 1.2 million people globally since December 2019. Although the host factors underpinning COVID-19 pathology are not fully understood, type I interferon (IFN-I) response is considered crucial for SARS-CoV-2 pathogenesis. Perturbations in IFN-I signaling and associated interferon-inducible genes (ISG) are among the primary disease severity indicators in COVID-19. Consequently, IFN-I therapy, either alone or in- combination with existing antiviral or anti-inflammatory drugs, is tested in many ongoing clinical trials to reduce COVID-19 mortality. Since signaling by the IFN-I family of molecules regulates host immune response to other infectious and non-infectious diseases, any imbalance in this family of cytokines would impact the clinical outcome of COVID-19, as well as other co-existing diseases. Therefore, it is imperative to evaluate the beneficial-versus-detrimental effects of IFN-I immunotherapy for COVID-19 patients with divergent disease severity and other co-existing conditions. This review article summarizes the role of IFN-I signaling in infectious and non-infectious diseases of humans. It highlights the precautionary measures to be considered before administering IFN-I to COVID-19 patients having other co-existing disorders. Finally, suggestions are proposed to improve IFN-I immunotherapy to COVID-19.

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THE ROLE OF MYELOPEROXIDASE AND NEUTROPHIL EXTRACELLULAR TRAPS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.009 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S4-S4

Author(s):

Belal Chami ◽

Gulfam Ahmad ◽

Angie Schroder ◽

Patrick San Gabriel ◽

Paul Witting

Keyword(s):

Disease Severity ◽

Hypochlorous Acid ◽

Tissue Injury ◽

Activity Index ◽

Critical Role ◽

Neutrophil Migration ◽

Sodium Sulphate ◽

Host Tissue ◽

Neutrophil Extracellular Trap

Abstract Neutrophils are short-lived immune cells that represent the major cell type recruited to the inflamed bowel releasing their azurophilic granules containing enzymes myeloperoxidase (MPO). Fecal and serum MPO levels has previously been shown to correlate to disease severity in IBD patients. MPO, in the presence of H2O2 and free Cl- undergoes a halogenation cycle, yielding the two-electron oxidant, hypochlorous acid (HOCl) - a potent bactericidal agent. However, chronic intestinal exposure to MPO/HOCl due to perpetual inflammation may cause secondary host-tissue injury and cell death. Neutrophil Extracellular Trap (NET)osis is a specialised form of neutrophil death where MPO is entrapped in a DNA scaffold and continues to elicit HOCl activity and may further contribute to host-tissue injury. We investigated the presence of NETs in surgically excised ileum samples from CD and healthy patients using advanced confocal microscopic techniques and found MPO, Neutrophil Elastase (NE) and Citrullinated Histone h3 (CitH3) - critical components of NET formation, individually positively correlate to the severity of histopathological intestinal injury. Furthermore, multiplex Opal™ IHC performed using LMS880 Airyscan-moduled microscopy with z-stacking revealed colocalization of NE, MPO, CitH3 and DAPI indicating the extensive presence of NETs in severely affected CD tissue. Using two pharmacological inhibitors of MPO in a dextran sodium sulphate (DSS) model of murine colitis, we demonstrated the pathological role of MPO in experimental colitis. MPO inhibitors, TEMPOL and AZD3241 delivered via daily i.p significantly rescued the course of colitis by abrogating clinical indices including body weight loss, disease activity index, inhibiting serum peroxidation, and preserving colon length, while significantly mitigating histoarchitectural damage associated with DSS-induced colitis. We also showed that MPO inhibition decreased neutrophil migration to the gut, suggesting MPO may play a role in perpetuating the inflammatory cell by further recruiting cells to the inflamed gut. Collectively, we have shown for the first time that MPO is not only an important clinical marker of disease severity but may also play a critical role in perpetuating host-tissue damage and inflammation.

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Is Bisphosphonate-Related Osteonecrosis of the Jaw an Infection? A Histological and Microbiological Ten-Year Summary

International Journal of Dentistry ◽

10.1155/2014/452737 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

A. M. Hinson ◽

C. W. Smith ◽

E. R. Siegel ◽

B. C. Stack

Keyword(s):

Systematic Review ◽

Disease Severity ◽

Large Scale ◽

Clinical Signs ◽

Signs And Symptoms ◽

Osteonecrosis Of The Jaw ◽

Multifactorial Disease ◽

Clinical Signs And Symptoms ◽

Surgical Treatments

The role of infection in the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is poorly understood. Large-scale epidemiological descriptions of the histology and microbiology of BRONJ are not found in the literature. Herein, we present a systematic review of BRONJ histology and microbiology (including demographics, immunocompromised associations, clinical signs and symptoms, disease severity, antibiotic and surgical treatments, and recovery status) validating that infection should still be considered a prime component in the multifactorial disease.

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