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1.
Front Cell Infect Microbiol ; 12: 850581, 2022.
Article in English | MEDLINE | ID: covidwho-1742206

ABSTRACT

Mucormycosis is an emerging infection caused by fungi of the order Mucorales that has recently gained public relevance due to the high incidence among COVID-19 patients in some countries. The reduced knowledge about Mucorales pathogenesis is due, in large part, to the historically low interest for these fungi fostered by their reluctance to be genetically manipulated. The recent introduction of more tractable genetic models together with an increasing number of available whole genome sequences and genomic analyses have improved our understanding of Mucorales biology and mucormycosis in the last ten years. This review summarizes the most significant advances in diagnosis, understanding of the innate and acquired resistance to antifungals, identification of new virulence factors and molecular mechanisms involved in the infection. The increased awareness about the disease and the recent successful genetic manipulation of previous intractable fungal models using CRISPR-Cas9 technology are expected to fuel the characterization of Mucorales pathogenesis, facilitating the development of effective treatments to fight this deadly infection.


Subject(s)
COVID-19 , Mucorales , Mucormycosis , Antifungal Agents/therapeutic use , Genomics , Humans , Mucorales/genetics , Mucormycosis/diagnosis , Mucormycosis/microbiology , Mucormycosis/pathology
2.
Diagn Cytopathol ; 50(3): 93-98, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1589136

ABSTRACT

BACKGROUND: COVID 19 has been rapidly spreading across the globe. As a result of alteration of the immune milieu by COVID 19 and its treatment, there has been a rise in opportunistic fungal infections particularly Mucormycosis in these patients. Delay in diagnosis of these fungal infections can be fatal. The usual diagnostic modalities used to detect Mucor include potassium hydroxide (KOH) mount, fungal culture, and histopathology. Since histopathology and fungal culture have a long turnaround time we are dependent on KOH mount for rapid results. Here we investigate the role of stained cytology smears in the rapid diagnosis of Mucormycosis. METHODS: A prospective observational study was conducted in a tertiary health care hospital on samples of patients clinically suspected to have Mucormycosis. We performed May Grunwald Giemsa (MGG) and Papanicolaou (PAP) stains on the remnant samples of nasal swabs/scrapings/biopsies after KOH test and fungal culture. We took 16 KOH positive and 16 KOH negative samples. We also examined 16 fresh samples from patients whose earlier samples were reported to be negative on KOH test. RESULTS: The 6/16 KOH positive samples were found to be positive on stained cytology smears and 2 were mixed infections wherein both Mucor and Aspergillus were seen. The 4/16 KOH negative samples were positive for Mucor with one sample having both Mucor and Aspergillus. The 3/16 repeat samples which were earlier negative on KOH test were positive for Mucor. CONCLUSION: Stained cytology smears if used in conjunction with KOH test can increase the overall sensitivity of detection of Mucormycosis and mixed infections.


Subject(s)
COVID-19/pathology , COVID-19/virology , Mucormycosis/pathology , Mucormycosis/virology , SARS-CoV-2/pathogenicity , Biopsy/methods , COVID-19/diagnosis , Female , Humans , Mucormycosis/diagnosis , Mycoses/diagnosis , Mycoses/pathology , Prospective Studies , Specimen Handling/methods , Vaginal Smears/methods
3.
J Med Virol ; 94(1): 99-109, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544351

ABSTRACT

A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Mucormycosis/epidemiology , Mucormycosis/mortality , SARS-CoV-2/isolation & purification , Diabetes Mellitus/pathology , Humans , Hyperglycemia/pathology , Immunocompromised Host/physiology , Mucorales/growth & development , Mucorales/isolation & purification , Mucormycosis/pathology , Retrospective Studies , Risk Factors
4.
Pan Afr Med J ; 39: 275, 2021.
Article in English | MEDLINE | ID: covidwho-1485483

ABSTRACT

Fungal osteomyelitis is a life-threatening and seldom seen opportunistic infection. It is commonly an affectation of the nose and paranasal sinuses within the orofacial region. It is an aggressive infection that needs to be addressed promptly to prevent fatal consequences. The mode of infection is via the inhalation route and infection begins initially in the nose and paranasal sinuses with subsequent invasion into the vascular tissue, eventually leading to thrombosis and necrosis of nearby hard and soft tissues. Here, we report a case of a 31-year-old male who presented with pain over the upper jaw that was sudden in onset, continuous, dull aching, radiating towards forehead and neck of the left side, aggravates on mastication and relives on its own. He had a history of uncontrolled diabetes mellitus. On further investigation, using diagnostic and Interventional aids, a final diagnosis of mucormycotic osteomyelitis of the maxilla was made.


Subject(s)
COVID-19/complications , Maxillary Diseases/diagnosis , Mucormycosis/diagnosis , Osteomyelitis/diagnosis , Adult , Diabetes Mellitus/physiopathology , Humans , Male , Maxillary Diseases/microbiology , Maxillary Diseases/pathology , Mucormycosis/pathology , Opportunistic Infections/diagnosis , Opportunistic Infections/microbiology , Opportunistic Infections/pathology , Osteomyelitis/microbiology , Osteomyelitis/pathology
6.
Mycoses ; 64(10): 1291-1297, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1367354

ABSTRACT

BACKGROUND: The enormous increase in COVID-19-associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID-19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. METHODS: We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID-19 subjects without mucormycosis (controls). RESULTS: We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc-enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc-augmented DRBC agar. A time- and concentration-dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. CONCLUSIONS: Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.


Subject(s)
COVID-19/epidemiology , Mucormycosis/epidemiology , Rhizopus oryzae/growth & development , Zinc Compounds/adverse effects , Zinc Compounds/metabolism , COVID-19/pathology , Case-Control Studies , Female , Humans , India/epidemiology , Male , Middle Aged , Mucormycosis/mortality , Mucormycosis/pathology , Rhizopus oryzae/isolation & purification , SARS-CoV-2/isolation & purification , Zinc Compounds/therapeutic use
8.
Mycoses ; 64(10): 1238-1252, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1314088

ABSTRACT

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.


Subject(s)
Antifungal Agents/therapeutic use , COVID-19/complications , Coinfection , Mucormycosis/drug therapy , Mucormycosis/mortality , Respiratory Distress Syndrome/mortality , Adolescent , Adult , Aged , Amphotericin B/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , Caspofungin/therapeutic use , Comorbidity , Cross-Sectional Studies , Diabetes Complications/microbiology , Diabetes Complications/mortality , Diabetes Mellitus/pathology , Drug Therapy, Combination , Female , Humans , Iran , Male , Middle Aged , Mucormycosis/pathology , Respiratory Distress Syndrome/microbiology , Respiratory Distress Syndrome/pathology , Triazoles/therapeutic use , Young Adult
9.
Diabetes Metab Syndr ; 15(4): 102196, 2021.
Article in English | MEDLINE | ID: covidwho-1293738

ABSTRACT

AIMS: Diabetes Mellitus predisposes patients to invasive fungal infections. There has been a recent surge of Mucormycosis with COVID 19 infection particularly in patients with diabetes. This study aims to study the clinical spectrum of CAM (COVID -associated Mucormycosis) with diabetes and subsequent outcomes. MATERIAL AND METHODS: This was a descriptive study conducted at a single COVID Care Centre in India in patients with COVID Associated Mucormycosis from April 12, 2021 to May 31, 2021. RESULTS: Among 953 hospitalized patients with COVID 19 infection, 32 patients had CAM with an incidence of 3.36%. In patients with CAM, 87.5% had Diabetes Mellitus as the most common co-morbidity. The majority of the patients had poor glycemic control with a mean HbA1c of 9.06%. Out of the total study population, 93% had prior exposure to high dose corticosteroids. During the study period, 12.5% patients of CAM did not survive. CONCLUSION: Mucormycosis is an angioinvasive fungal infection with high mortality. The disease has surged in COVID 19 pandemic due to uncontrolled diabetes and improper corticosteroid use.


Subject(s)
COVID-19/complications , Diabetes Mellitus/physiopathology , Hospitalization/statistics & numerical data , Mucormycosis/mortality , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Diabetes Mellitus/virology , Female , Humans , India/epidemiology , Male , Middle Aged , Mucormycosis/epidemiology , Mucormycosis/pathology , Mucormycosis/virology , Prognosis , Risk Factors , Survival Rate
10.
Diabetes Metab Syndr ; 15(4): 102146, 2021.
Article in English | MEDLINE | ID: covidwho-1240285

ABSTRACT

BACKGROUND AND AIMS: There are increasing case reports of rhino-orbital mucormycosis in people with coronavirus disease 2019 (COVID-19), especially from India. Diabetes mellitus (DM) is an independent risk factor for both severe COVID-19 and mucormycosis. We aim to conduct a systematic review of literature to find out the patient's characteristics having mucormycosis and COVID-19. METHODS: We searched the electronic database of PubMed and Google Scholar from inception until May 13, 2021 using keywords. We retrieved all the granular details of case reports/series of patients with mucormycosis, and COVID-19 reported world-wide. Subsequently we analyzed the patient characteristics, associated comorbidities, location of mucormycosis, use of steroids and its outcome in people with COVID-19. RESULTS: Overall, 101 cases of mucormycosis in people with COVID-19 have been reported, of which 82 cases were from India and 19 from the rest of the world. Mucormycosis was predominantly seen in males (78.9%), both in people who were active (59.4%) or recovered (40.6%) from COVID-19. Pre-existing diabetes mellitus (DM) was present in 80% of cases, while concomitant diabetic ketoacidosis (DKA) was present in 14.9%. Corticosteroid intake for the treatment of COVID-19 was recorded in 76.3% of cases. Mucormycosis involving nose and sinuses (88.9%) was most common followed by rhino-orbital (56.7%). Mortality was noted in 30.7% of the cases. CONCLUSION: An unholy trinity of diabetes, rampant use of corticosteroid in a background of COVID-19 appears to increase mucormycosis. All efforts should be made to maintain optimal glucose and only judicious use of corticosteroids in patients with COVID-19.


Subject(s)
COVID-19/complications , Mucormycosis/epidemiology , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Humans , India/epidemiology , Mucormycosis/pathology , Mucormycosis/virology , Prognosis , Risk Factors
11.
Lancet Microbe ; 1(6): e245-e253, 2020 10.
Article in English | MEDLINE | ID: covidwho-1065709

ABSTRACT

BACKGROUND: Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19. METHODS: In this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients. FINDINGS: The median age at death of our cohort of ten patients was 73 years (IQR 52-79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients. INTERPRETATION: Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19. FUNDING: Imperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.


Subject(s)
COVID-19 , Mucormycosis , Pancreatitis , Pericarditis , Thrombosis , Acute Disease , COVID-19/epidemiology , Humans , Infarction/pathology , Lung/pathology , Mucormycosis/pathology , Pancreatitis/pathology , Pericarditis/pathology , SARS-CoV-2 , Thrombosis/pathology , United Kingdom/epidemiology , Viral Tropism
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