Deficient Phagocytosis in Circulating Monocytes from Patients with COVID-19-Associated Mucormycosis

Sinha, Bishnu Prasad; Mehta, Priyanka; Hoque, Md. Asmaul; Bandopadhyay, Purbita; Nandi, Ayandip; Saha, Ipsita; Mitra, Anita Nandi; Mondal, Asish; Bhattacharjee, Boudhayan; Chamilos, Georgios; Pandey, Rajesh; Basu, Kaushik; Ganguly, Dipyaman

doi:10.1128/mbio.00590-23

Cited by 2 publications

(3 citation statements)

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“…Complement cascade features in the pathophysiology of COVID‐19 and mucormycosis, and links the innate and adaptive immune responses 49 . The cofactor F1 and complement receptors CR1 and CR3 were upregulated in both monocytes and neutrophils in CAPM versus control cohort and may enhance phagocytosis 9 . Interestingly, the complement inhibitors, clusterin and CD59 were upregulated in the monocytes and neutrophils from the CAPM cohort.…”

Section: Discussionmentioning

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%

“…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%

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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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Section: Discussionmentioning

confidence: 99%