Pathogenetic factors fanning the flames of COVID-19 to cause rhino-orbito-cerebral mucormycosis: An observational study

Reddy, Y Muralidhar; Yeduguri, Sreekanth; N, Vishnu swaroop Reddy; Parida, Subhendu; Kamatham, Shanti Naidu; Pidaparthi, Lalitha; Jaiswal, Shyam K; Sadhvani, Bhavana; Tourani, Vijaya; Kumar, Sunil; Challa, Sundaram; Murthy, J. M. K.

doi:10.1016/j.mycmed.2022.101252

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…IL-6 levels were also increased with mean levels similar to those observed in another study. [ 38 ] However, the levels for all stages were not significantly different. In our study, the mean level of IL-6 in patients who died was 71.3 pg/ml, which is concurrent with a similar study from South India that found levels significantly greater than 70 pg/ml in patients who died of COVID-19.…”

Section: Discussionmentioning

confidence: 93%

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India

Kumari

Ranjan

Nishant

et al. 2023

Indian Journal of Ophthalmology

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Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant ( P = 0.31). IL-6 values for all stages were similar ( P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages ( P = 0.04). IL-6 was significantly lower ( P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light ( P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

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Section: Discussionmentioning

confidence: 93%

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India

Kumari

Ranjan

Nishant

et al. 2023

Indian Journal of Ophthalmology

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“…COVID-19 patients were shown to be infected with acute invasive rhino-orbital mucormycosis, which is a highly morbid infection that primarily affects immunosuppressed individuals [ 62 ]. In another study, 31 patients with COVID-19-associated rhino-orbito-cerebral mucormycosis (CAROCM) were included, in which a higher incidence of uncontrolled diabetes and renal dysfunction was recorded, while levels of IL-6, ferritin, and D-dimer were significantly higher in CAROCM than in non-mucormycosis patients [ 63 ].…”

Section: Mucormycosis and Sars-cov-2 Comorbiditymentioning

confidence: 99%

An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight

et al. 2023

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The novel pathogenic virus was discovered in Wuhan, China (December 2019), and quickly spread throughout the world. Further analysis revealed that the pathogenic strain of virus was corona but it was distinct from other coronavirus strains, and thus it was renamed 2019-nCoV or SARS-CoV-2. This coronavirus shares many characteristics with other coronaviruses, including SARS-CoV and MERS-CoV. The clinical manifestations raised in the form of a cytokine storm trigger a complicated spectrum of pathophysiological changes that include cardiovascular, kidney, and liver problems. The lack of an effective treatment strategy has imposed a health and socio-economic burden. Even though the mortality rate of patients with this disease is lower, since it is judged to be the most contagious, it is considered more lethal. Globally, the researchers are continuously engaged to develop and identify possible preventive and therapeutic regimens for the management of disease. Notably, to combat SARS-CoV-2, various vaccine types have been developed and are currently being tested in clinical trials; these have also been used as a health emergency during a pandemic. Despite this, many old antiviral and other drugs (such as chloroquine/hydroxychloroquine, corticosteroids, and so on) are still used in various countries as emergency medicine. Plant-based products have been reported to be safe as alternative options for several infectious and non-infectious diseases, as many of them showed chemopreventive and chemotherapeutic effects in the case of tuberculosis, cancer, malaria, diabetes, cardiac problems, and others. Therefore, plant-derived products may play crucial roles in improving health for a variety of ailments by providing a variety of effective cures. Due to current therapeutic repurposing efforts against this newly discovered virus, we attempted to outline many plant-based compounds in this review to aid in the fight against SARS-CoV-2.

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“…Under stressful conditions, this is trans-located from ER to cell surface. Viral replication in the cell leads to the accumulation of excessively high number of unfolded viral structural proteins in ER leading to over expression of GRP78, at the cell surface [ 35 ]. GRP78 is also the receptor used by Mucorales, especially Rhizopus spp.…”

Section: Factors Favoring Cammentioning

confidence: 99%

“…Uncontrolled DM and newly diagnosed DM at the evaluation for CAM were reported in several series [ 19 ••, 24 ••, 34 ]. DKA and acute or chronic renal dysfunction were reported in 20% of patients with COVID-associated ROCM [ 35 ]. Corticosteroids were indicated for the treatment of hospitalized patients with COVID-19 pneumonia who required supplemental oxygen and higher levels of respiratory support [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis and Pathology of COVID-Associated Mucormycosis: What Is New and Why

Radotra

Challa

2022

Curr Fungal Infect Rep

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Purpose of Review There is global increase in the incidence of mucormycosis. However, a sudden increase in the COVID-associated mucormycosis (CAM) was noted, particularly in India, during the second wave of the COVID-19 pandemic. The interplay of factors involved in the pathogenesis is complex. In this review, the influence of pre-existing disease, exaggerated risk factors, altered milieu due to COVID-19 itself and the consequences of its treatment on the host pathogen interactions leading to the disease and morphology of the fungus will be highlighted. Recent Findings Hyperglycemia, acidosis, available free iron, lowered host defenses, and the fungal virulence factors promote the growth of Mucorales. There is a high background prevalence of diabetes mellitus (DM) in India. Uncontrolled or undiagnosed DM, COVID-19 itself, and inappropriate administration of corticosteroids in high doses and for prolonged periods result in hyperglycemia. Diabetic ketoacidosis (DKA) and metabolic acidosis due to hypoxia or renal failure contribute to acidic pH and dissociate bound iron from serum proteins. The host defenses are lowered due to COVID-19-induced immune dysregulation, hyperglycemia itself, and administration of corticosteroids and immune suppressants for the treatment of COVID-19. The altered metabolic milieu in the local microenvironment of nose and paranasal sinuses (PNS) promotes specific interaction of glucose-regulated protein-78 (GRP-78) on host cells with spore coat protein homologue (CotH 3) on Mucorales resulting in rhino-orbito-cerebral mucormycosis (ROCM) as the predominant clinical form in CAM. The pathology is extensive soft tissue involvement with angioinvasion and perineural invasion. Melanized hyphae and sporangia were seen on histopathology, which is unique to CAM. While many factors favor the growth of Mucorales in CAM, hyperglycemia, hyperferritinemia, and administration of hyperbaric oxygen result in reactive oxygen species (ROS) and inadequate humidification results in dehydration. Melanization is possibly the adaptive and protective mechanism of Mucorales to escape the unfavorable conditions due to the treatment of COVID-19. Summary High background prevalence of DM, inappropriate administration of corticosteroids and immune dysregulation due to COVID-19 favor the growth of Mucorales in CAM. Melanization of Mucorales hyphae and sporangia on histopathology probably represent adaptive and protective mechanism due to the treatment with hyperbaric oxygen with inadequate humidification as well as the metabolic alterations.

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Pathogenetic factors fanning the flames of COVID-19 to cause rhino-orbito-cerebral mucormycosis: An observational study

Cited by 6 publications

References 25 publications

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India

An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight

Pathogenesis and Pathology of COVID-Associated Mucormycosis: What Is New and Why

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