Utility of MGG and Papanicolaou stained smears in the detection of Mucormycosis in nasal swab/scraping/biopsy samples of COVID 19 patients.

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.

Case Report: Rhino-orbital Mucormycosis Related to COVID-19: A Case Series Exploring Risk Factors.

There has been a surge of rhino-orbital mucormycosis cases in India in the wake of the second wave of the COVID-19 pandemic. It has been widely suggested that dysglycemia resulting from diabetes which is a common comorbidity in COVID-19 patients, and indiscriminate steroid use has resulted in this surge. We report a series of 13 cases of rhino-orbital mucormycosis in COVID-19 patients admitted to our center between mid-April and early June 2021. The cases showed a male preponderance, two patients had loss of vision, and four of them showed intracranial extension of disease. Twelve patients had received steroids and 12 had preexisting or newly diagnosed diabetes, both steroid use and diabetes being the most common identified risk factors. Considering other possible risk factors, immunosuppressed state, antiviral or ayurvedic (Indian traditional) medications, and oxygen therapy were not associated with a definite risk of mucormycosis, because they were not present uniformly in the patients. We propose that COVID-19 itself, through molecular mechanisms, predisposes to mucormycosis, with other factors such as dysglycemia or steroid use increasing the risk.

COVID-19-associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic's second wave in India.

Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19-induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19-associated mucormycosis in India.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Coronavirus disease 2019 associated mucormycosis meandering its way into the orbit: a pictorial review.

BACKGROUND: There has been a recent deluge of coronavirus disease 2019 associated mucormycosis in our country. It affects the paranasal sinuses; however, it has a rapid extrasinus progression (the orbit being most common), which can be fatal if not detected early. It may meander into the orbit through various foramina without frank bone destruction. METHODS: This paper reviews the various gateways of the spread of coronavirus disease 2019 associated mucormycosis to the orbit, even before advent of bone destruction or ocular symptoms. Plausible pathways of invasion and subtle imaging findings are depicted, to enable an early diagnosis. RESULTS: Relevant anatomy and imaging examples have been illustrated to familiarise the surgeons with various routes of coronavirus disease 2019 associated mucormycosis spread to the orbit. Emphasis is laid on searching for subtle imaging findings for the detection of early orbital invasion. CONCLUSION: Early detection and extension of coronavirus disease 2019 associated mucormycosis is facilitated by knowledge of its gateways of spread, which aids the surgeon in prognostication and planning of the surgical approach.

Rampant Increase in Cases of Mucormycosis in India and Pakistan: A Serious Cause for Concern during the Ongoing COVID-19 Pandemic.

COVID-19 is a global health crisis that continues to pose new challenges all around the world. Amidst the growing pandemic, a spike in the number of mucormycosis cases in India and Pakistan has been reported in COVID-19 patients and in those who have recovered from COVID-19. This increase in cases may be related to the overuse of steroids and zinc, the use of industrial oxygen, unsterilized medical equipment, frequent intubation, a weakened immune system, and pre-existing comorbidities such as diabetes. As a result, it is critical to take steps to handle the current increase in mucormycosis cases. Therefore, this article aims to highlight the existence of mucormycosis amidst the COVID-19 pandemic in India and Pakistan, focusing on possible causes and implications, and suggests important plans of action to be taken during this pandemic.

Absence of Case of Mucormycosis (March 2020-May 2021) under strict protocol driven management care in a COVID-19 specific tertiary care intensive care unit.

AIMS: With a sudden increase in cases of mucormycosis seen in Covid -19 patients, we conducted a retrospective analysis of all admitted patients in a tertiary care covid-19 hospital looking at incidence of mucormycosis. METHODS: Intensive care unit daily rounds data stored in an electronic format was retrieved by one of the consultants, looking for incidence of mucormycosis, diabetes mellitus, adherence to protocol for steroid use, glycemic control and use of monoclonal antibodies. Also, patients follow up data base of post covid Outpatients Department was searched for cases of mucormycosis. RESULTS: A total of 5248 patients were admitted between March 2020 to May 2021, of which 1027 were in ICU and 4221 in wards. Of the 1027 patients admitted in Intensive care unit, 915 received steroids and 417 had diabetes as existing co-morbidity. No case of mucormycosis was reported during the stay in the hospital and during immediate outpatient department follow up. The low dose steroids were administered as per state government protocol for treating COVID 19, a nurse driven strict glycemic control regime (blood glucose level was maintained between 140 and 180 mg/dl through the admission in ICU and was achieved consistently in 842 (82%) patients, followed along with minimal use of other immunomodulatory like monoclonal antibodies. CONCLUSION: A strict adherence to protocol of low dose steroids coupled with strict glycemic control helped in eliminating the risk and incidence of mucormycosis in a tertiary care dedicated covid-19 hospital.

Diabetes, COVID 19 and mucormycosis: Clinical spectrum and outcome in a tertiary care medical center in Western India.

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.

Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India.

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.

COVID-19-associated mucormycosis: An updated systematic review of literature.

In its wake, the COVID-19 pandemic has ushered in a surge in the number of cases of mucormycosis. Most cases are temporally linked to COVID-19; hence, the entity is described as COVID-19-associated mucormycosis (CAM). The present systematic review was undertaken to provide an up-to-date summary of the hitherto available literature on CAM. PubMed, Scopus and Google Scholar databases were systematically searched using appropriate keywords till 14 May 2021, to identify case reports/case series pertaining to mucormycosis in patients with COVID-19. Relevant data extracted included demographic characteristics, comorbidity profile, clinical category of mucormycosis, glucocorticoid use, treatment offered and patient outcome. We identified 30 case reports/case series, pooling data retrieved from 99 patients with CAM. Most cases were reported from India (72%). The majority of the patients was male (78%) and had diabetes mellitus (85%). A prior history of COVID-19 was present in 37% patients with mucormycosis developing after an initial recovery. The median time interval between COVID-19 diagnosis and the first evidence of mucormycosis infection or CAM diagnosis was 15 days. Glucocorticoid use was reported in 85% of cases. Rhino-orbital mucormycosis was most common (42%), followed by rhino-orbito-cerebral mucormycosis (24%). Pulmonary mucormycosis was observed in 10 patients (10%). The mortality rate was 34%; the use of adjunct surgery, which was undertaken in 81% of patients, was associated with better clinical outcomes (p < .001). In conclusion, CAM is an emerging problem necessitating increased vigilance in COVID-19 patients, even those who have recovered. CAM portends a poor prognosis and warrants early diagnosis and treatment.

Mucormycosis with orbital compartment syndrome in a patient with COVID-19.

During the current pandemic of COVID-19, a myriad of manifestations and complications has emerged and are being reported on. We are discovering patients with COVID-19 are at increased risk of acute cardiac injury, arrythmias, thromboembolic complications (pulmonary embolism and acute stroke), and secondary infection to name a few. I describe a novel case of COVID-19 in a previously healthy 33-year-old female who presented for altered mental status and proptosis. She was ultimately diagnosed with mucormycosis and orbital compartment syndrome, in addition to COVID-19. Early identification of these high morbidity conditions is key to allow for optimal treatment and improved outcomes.

[Trichodysplasia spinulosa. Report of one case]. / Tricodisplasia espinulosa asociada a síndrome mielodisplásico e inmunosupresión.

Trichodysplasia spinulosa is a rare disease that occurs in the setting of immunosuppression, associated with tolerogenic therapy used in allograft recipients or patients with hematologic malignancies. Clinically, it is characterized by a centrofacial cutaneous eruption of erythematous papules with a central keratinous spicule, often associated with variable degrees of alopecia. Histologic findings are characteristic, and electron microscopy reveals the presence of trichodysplasia spinulosa associated polyomavirus. We report a 47-year-old woman with idiopathic autoimmune pancytopenia refractory to diverse immunosuppressant regimens, with clinical and pathologic findings compatible with the disease, in whom complementary studies were required to exclude other differential diagnoses.

Tricodisplasia espinulosa asociada a síndrome mielodisplásico e inmunosupresión / Trichodysplasia spinulosa: report of one case

Trichodysplasia spinulosa is a rare disease that occurs in the setting of immunosuppression, associated with tolerogenic therapy used in allograft recipients or patients with hematologic malignancies. Clinically, it is characterized by a centrofacial cutaneous eruption of erythematous papules with a central keratinous spicule, often associated with variable degrees of alopecia. Histologic findings are characteristic, and electron microscopy reveals the presence of trichodysplasia spinulosa associated polyomavirus. We report a 47-year-old woman with idiopathic autoimmune pancytopenia refractory to diverse immunosuppressant regimens, with clinical and pathologic findings compatible with the disease, in whom complementary studies were required to exclude other differential diagnoses.

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis.

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies.

Isolated case of Ebola hemorrhagic fever with mucormycosis complications, Kinshasa, Democratic Republic of the Congo.

A patient with undiagnosed Ebola (EBO) hemorrhagic fever (EHF) was transferred from Kikwit to a private clinic in Kinshasa, Democratic Republic of the Congo. A diagnosis of EHF was suspected on clinical grounds and was confirmed by detection of EBO virus-specific IgM and IgG in serum of the patient. During the course of the disease, although she had no known predisposing factors, the patient developed a periorbital mucormycosis abscess on eyelid tissue that was biopsied during surgical drainage; the abscess was histologically confirmed. Presence of EBO antigen was also detected by specific immunohistochemistry on the biopsied tissue. The patient survived the EBO infection but had severe sequelae associated with the mucormycosis. Standard barrier-nursing precautions were taken upon admission and upgraded when EHF was suspected; there was no secondary transmission of the disease.