Perturbations of immune landscape in COVID‐19 associated mucormycosis

Desai, Nidhi; Pradhan, Vandana; Chougule, Durga; Tiwari, Smrati; Mandke, Charuta; Yadav, Reetika Malik; Athvale, Amita; Kawle, Juhi; Pai, Vinayak; Pawaskar, Swapnal; Kharkar, Harshada; Bhosale, Snehal; Parab, Ankita; Ansari, S M Razaullah; Kumar, Kinnera Harish; Mhashal, Shashikant; Redkar, Neelam; Madkaikar, Manisha

doi:10.1111/myc.13546

Cited by 5 publications

(4 citation statements)

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“…If any spores survive and germinate, then hyphae trigger neutrophils chemotaxis, which kills the germinated spores through the production of pro-inflammatory cytokines, such as tumor necrosis factor-α, interferon (IFN)-γ, and interleukin (IL)-1β, and reactive oxygen metabolites, cationic peptides, perforin which attracts and activate other immune cells. [18] Due to the strong binding of platelets to mucorale spores and hyphae, they also contribute to the host's immune response during infection. As soon as the platelets bind to the pathogen and get activated, they start to destroy the hyphae by secreting the granular pro-and anti-inflammatory cytokines and chemokines having antifungal properties.…”

Section: Pathogenesismentioning

confidence: 99%

“…If any spores survive and germinate, then hyphae trigger neutrophils chemotaxis, which kills the germinated spores through the production of pro‐inflammatory cytokines, such as tumor necrosis factor‐α, interferon (IFN)‐γ, and interleukin (IL)‐1β, and reactive oxygen metabolites, cationic peptides, perforin which attracts and activate other immune cells. [ 18 ]…”

Section: Pathogenesismentioning

confidence: 99%

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An extensive review on antifungal approaches in the treatment of mucormycosis

Chaudhari,

Palkar,

Abha Mishra

et al. 2023

J Biochem & Molecular Tox

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During the period of COVID‐19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first‐line therapy (monotherapy) and combination therapy. Amphotericin B (1) and isavuconazole (2) are the drugs of choice for first‐line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole (3) and deferasirox (4) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first‐line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT‐1161 (5) and APX001A (6), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.

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Section: Pathogenesismentioning

confidence: 99%

Section: Pathogenesismentioning

confidence: 99%

An extensive review on antifungal approaches in the treatment of mucormycosis

Chaudhari,

Palkar,

Abha Mishra

et al. 2023

J Biochem & Molecular Tox

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“…The immunological status of patients who develop pulmonary mucormycosis post SARS‐CoV‐2 infection is unclear 6,8 . Few studies from India highlighted the clinical and immunological characteristics observed among CAPM patients 9,10 . In a pan‐India case–control study, several previously known host factors, such as organ transplantation, diabetes mellitus and immunosuppression, were implicated in CAPM 11,12 .…”

Section: Introductionmentioning

confidence: 99%

“…6,8 Few studies from India highlighted the clinical and immunological characteristics observed among CAPM patients. 9,10 In a pan-India case-control study, several previously known host factors, such as organ transplantation, diabetes mellitus and immunosuppression, were implicated in CAPM. 11,12 The treatment regime for COVID-19 patients (with glucocorticoids and zinc supplementation) was also identified as a risk factor, significantly associated with CAPM.…”

Section: Introductionmentioning

confidence: 99%

Immune and metabolic perturbations in COVID‐19‐associated pulmonary mucormycosis: A transcriptome analysis of innate immune cells

Dhaliwal,

Muthu,

Sharma

et al. 2023

Mycoses

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Background and ObjectivesThe mechanisms underlying COVID‐19‐associated pulmonary mucormycosis (CAPM) remain unclear. We use a transcriptomic analysis of the innate immune cells to investigate the host immune and metabolic response pathways in patients with CAPM.Patients and MethodsWe enrolled subjects with CAPM (n = 5), pulmonary mucormycosis (PM) without COVID‐19 (n = 5), COVID‐19 (without mucormycosis, n = 5), healthy controls (n = 5) without comorbid illness and negative for SARS‐CoV‐2. Peripheral blood samples from cases were collected before initiating antifungal therapy, and neutrophils and monocytes were isolated. RNA sequencing was performed using Illumina HiSeqX from monocytes and neutrophils. Raw reads were aligned with HISAT‐2 pipeline and DESeq2 was used for differential gene expression. Gene ontology (GO) and metabolic pathway analysis were performed using Shiny GO application and R packages (ggplot2, Pathview).ResultsThe derangement of core immune and metabolic responses in CAPM patients was noted. Pattern recognition receptors, dectin‐2, MCL, FcRγ receptors and CLEC‐2, were upregulated, but signalling pathways such as JAK–STAT, IL‐17 and CARD‐9 were downregulated; mTOR and MAP‐kinase signalling were elevated in monocytes from CAPM patients. The complement receptors, NETosis, and pro‐inflammatory responses, such as S100A8/A9, lipocalin and MMP9, were elevated. The major metabolic pathways of glucose metabolism—glycolysis/gluconeogenesis, pentose phosphate pathway, HIF signalling and iron metabolism‐ferroptosis were also upregulated in CAPM.ConclusionsWe identified significant alterations in the metabolic pathways possibly leading to cellular iron overload and a hyperglycaemic state. Immune responses revealed altered recognition, signalling, effector functions and a pro‐inflammatory state in monocytes and neutrophils from CAPM patients.

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