Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Progressive multifocal leukoencephalopathy in a patient with B-cell chronic lymphocytic leukemia after COVID-19 vaccination, complicated with COVID-19 and mucormycosis: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. CASE PRESENTATION: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. CONCLUSION: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis.

Oral mucormycosis associated with COVID-19 and diabetes mellitus: Case report and literature review / Mucormicosis oral asociada a COVID-19 y diabetes mellitus: descripción de un caso.

Mucormycosis is an invasive opportunistic fungal infection with high mortality, mainly detected in people with COVID-19, especially those with underlying diseases such as diabetes mellitus. Mucormycosis prevalence is 0.005 to 1.7 cases per million inhabitants, and it has been increasing in countries like India and Pakistan. This mycosis can affect different organs, and clinical manifestations reflect the transmission mechanism. Frequent forms are rhino-orbital-cerebral and pulmonary. This disease should be suspected in patients with necrotic injuries on mucous membranes or skin. We present a case of a patient with diabetes mellitus and diagnosed with oral mucormycosis associated with COVID-19.

La mucormicosis es una infección fúngica oportunista e invasiva, con una elevada tasa de mortalidad. Se ha detectado principalmente en pacientes con COVID-19, especialmente en personas con enfermedades concomitantes como la diabetes mellitus. La prevalencia de las mucormicosis es de 0,005 a 1,7 casos por millón de habitantes y ha ido en aumento en países como India y Pakistán; puede afectar diferentes órganos y su forma clínica refleja el mecanismo de transmisión. Entre las formas frecuentes están la rino-orbital-cerebral y la pulmonar, por ello, debe sospecharse mucormicosis en los pacientes con lesiones necróticas en mucosas o piel. Se presenta el caso de un paciente con antecedentes de diabetes mellitus que fue diagnosticado con mucormicosis oral asociada a la COVID-19.

Bell's palsy: a case report of unusual presentation in a patient with rhino-orbital cerebral mucormycosis.

BACKGROUND: Mucormycosis is a fungal infection caused by the Mucorales order of fungi. This fungus is commonly found in soil and can cause disease in immunocompromised patients. On the other hand, Bell's palsy is an idiopathic condition that results in the sudden onset of unilateral facial muscle weakness, affecting the facial nerve. CASE PRESENTATION: A 51-year-old Persian housewife with a history of poorly controlled diabetes mellitus presented with a splitting headache that had been ongoing for 1 week and an inability to close her left eye or make facial expressions on the left side of her face. The patient's vital signs were normal, but physical examination revealed a yellow-grey scar on the left side of her hard palate and Bell's palsy on the left side. A neurological examination showed that she could move both eyes but could not close her left eye, move up her left eyebrow, or smile. Further investigations were performed, including laboratory tests, radiologic imaging, and functional endoscopic sinus surgery. The patient underwent three rounds of debridement for bony erosion in the medial and posterior walls of the left maxillary sinus and the hard palate. Pathological examination confirmed mucormycosis infection in the hard palate and mucosa. CONCLUSION: Fungal infection must be considered a potential diagnosis for immunocompromised adults who exhibit symptoms of Bell's palsy.

Mixed Aspergillosis and Mucormycosis Infections in Patients with COVID-19: Case Series and Literature Review.

BACKGROUND: Mucormycosis and aspergillosis are angioinvasive infections mainly occurring in immunocompromised patients. However, mixed infection with mucormycosis and aspergillosis in post-COVID-19 patients is rare. In this report, we will report four cases and comprehensively review the published literature on COVID-19 associated mixed infection of aspergillosis and mucormycosis. METHOD: Besides four of our cases, we searched for published articles using PubMed/MEDLINE, Scopus, and Web of Science databases from the beginning of 2020 until October 2023. RESULT: During the COVID-19 pandemic, we analyzed 52 cases (4 from our research and 48 from other studies). The most common underlying disease (59.6%) was diabetes mellitus. However, 19.2% of COVID-19 patients had no underlying condition. Interestingly, rhino-orbital-cerebral mucormycosis featured prominently in India and Iran, while other countries primarily reported a higher prevalence of pulmonary cases. CONCLUSION: In conclusion, this study highlights the presence of mixed aspergillosis and mucormycosis in COVID-19 patients who previously had common underlying diseases or even a healthy immune system. Therefore, managing COVID-19 patients should involve screening serum and respiratory samples using biomarkers to detect superinfections.

Mucormycosis mimicking portal hypertensive haemorrhage as a complication of alcoholic liver cirrhosis: a case report.

Mucor is a rare cause of gastrointestinal ulcers. This case describes a case of mucormycosis that occurred in a patient with liver cirrhosis who was hospitalized to accept a splenectomy for traumatic splenic rupture. During the perioperative period, the patient developed upper gastrointestinal bleeding(UGIB), which was diagnosed as mucormycosis-related gastric ulcer according to gastroscopy. Patients with liver cirrhosis often get UGIB for Portal hypertension, but they also can develop UGIB for multiple other reasons, including infectious ulcers for immunosuppression. The case emphasizes the importance of excluding fungal-induced ulcer haemorrhage before diagnosing Portal hypertensive-induced variceal haemorrhage in patients with liver cirrhosis.

Angioinvasive gastrointestinal mucormycosis with duodenal necrosis and perforation in a patient with visceral myopathy.

A 55-year-old woman with a past medical history of visceral myopathy with multiple resultant abdominal surgeries, colectomy caused by severe pseudo-obstruction, and end-stage renal disease on hemodialysis presented with complaints of nausea, abdominal distention, vomiting, and diarrhea for five days. Small-bowel obstruction was identified on CT. She subsequently developed acute gastrointestinal bleeding, anemia, and hemodynamic instability. Extensive gastric ulceration with frank hemorrhage prompted urgent subtotal gastrectomy with multiple intraoperative findings, including a necrotic distal duodenum. Surgical pathology showed invasive fungal infection of the duodenum with perforation, morphologically compatible with invasive mucormycosis. The patient was started on intravenous liposomal amphotericin B, but despite best efforts, the patient ultimately succumbed to this invasive fungal infection in addition to sepsis and multi-organ failure.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Mucormycosis-induced hypercalcemia: a case report.

Hypercalcemia is a vital laboratory marker because it can show underlying severe diseases like cancer and infections. Of all the causes of hypercalcemia, primary hyperparathyroidism, and malignancies are the most common, but granulomatous diseases, such as certain fungal infections, can also be the cause. Here we describe the case of a 29-year-old woman, an insulin-dependent diabetic, found unconscious and tachypneic at home. In the emergency room, the medical team diagnosed diabetic ketoacidosis (DKA) and acute kidney injury (AKI). During hospitalization, despite resolving acidemia, persistent hypercalcemia attracted attention. Laboratory tests showed decreased parathyroid hormone (PTH) levels, confirming non-PTH-dependent hypercalcemia. Computed tomography (CT) of the chest and abdomen demonstrated no alterations, but an upper digestive endoscopy revealed an ulcerated and infiltrative lesion in the stomach. A biopsy showed a granulomatous infiltrate due to mucormycosis infection. The patient received liposomal amphotericin B for 30 days and isavuconazonium for two months. Serum calcium levels improved during treatment. Inquiry of the etiology of hypercalcemia should begin with the PTH assay; high levels are consistent with hyperparathyroidism; low levels, with calcium or vitamin D intoxication, malignancies, prolonged immobilization, and granulomatous diseases. In the latter cases, the overproduction of 1-alpha-hydroxylase by the granulomatous tissue increases the conversion of 25(OH)vitamin D into 1-25(OH)vitamin D, which causes the intestinal absorption of calcium. We have described the first hypercalcemia related to mucormycosis infection in a young diabetic patient, although case presentations associate other fungal infections with elevated serum calcium.

Maxillary mucormycosis and aspergillosis in post-COVID-19 patients in Mexico: A case series.

BACKGROUND: Fungal infections, during or as a consequence of SARS-CoV-2 infection, associated with uncontrolled diabetes mellitus and indiscriminate use of corticosteroids have been reported. In the jaw, mostly mucormycosis has been diagnosed in hospitals. METHODS: A retrospective, cross-sectional, descriptive study of the clinical, imaging, and histopathologic characteristics of maxillary invasive fungal infection in post-COVID-19 patients diagnosed in a private non-hospital oral pathology service in Mexico during 2020-2022 was conducted. RESULTS: We found 20 cases of maxillary invasive fungal infections in post-COVID-19 patients, 75% including a diagnosis of mucormycosis and 25% diagnosed as probable aspergillosis. The most common signs and symptoms were exposed necrotic bone followed by tooth mobility, discharge, and pain. On imaging, unilateral maxillary sinus involvement was observed in 6 cases (30%), and bilateral maxillary sinus involvement was observed in 3 cases (15%). CONCLUSIONS: It is essential to consider the association of osteonecrosis of the jaw in post-COVID-19 patients, with aspergillosis, not only mucormycosis, for early diagnosis and appropriate treatment.

Mucormycosis of the Mandible and Tongue: A Systematic Scoping Review.

AIM: Mucormycosis is a rare human infection associated with Mucorales, a group of filamentous moulds found in different environmental niches. Its oral manifestations may occur in the mandible and tongue despite being rare. We aimed to systematically review the data on clinical manifestations, risk factors, diagnostic approaches, treatment options, and outcomes of mandibular and tongue mucormycosis. METHODS: An electronic search of articles published between January 1975 and November 2022 in PubMed, Web of Science, and EMBASE databases was performed. A total of 22 articles met the inclusion criteria and reported 27 cases of oral mucormycosis in total. RESULTS: Fourteen patients had mandibular mucormycosis signs unrelated to COVID-19 infection, 6 had SARS-CoV-2-related mandibular mucormycosis, and 6 had manifestations in the tongue. All published case reports during the COVID-19 pandemic were from India. Patient ages ranged from 4 months old to 82 years, and most patients had important comorbidities, such as blood dyscrasias related to immune deficiency and uncontrolled type 2 diabetes mellitus. The signs and symptoms of mandibular and tongue mucormycosis varied from dental pain, loose teeth, and nonhealing sockets to dysphagia and paraesthesia of the lip. Some patients also reported trismus, draining sinus tract, and facial pain. The diagnosis of oral mucormycosis was based on a combination of clinical, radiographic, and histopathologic findings by demonstrating fungal hyphae in tissue specimens. In most cases, mucormycosis was managed with systemic amphotericin B, strict glycaemic control, and aggressive surgical debridement of infected tissue, minimising the progression of the fungal infection and thus improving the survival rate. In some cases, combined antifungal therapy, antibiotic therapy, and chlorhexidine mouthwashes were used successfully. CONCLUSIONS: Recognition of the signs and symptoms by oral care providers is pertinent for the early diagnosis and treatment of tongue and mandibular mucormycosis, and providers should be aware of the possibility of this opportunistic fungal infection in patients with COVID-19. A multidisciplinary approach is recommended for the management of this lethal infection.

Survival benefit of exenteration in COVID-19-associated rhino-orbital mucormycosis.

PURPOSE: There has been a sudden increase in the number of rhino-orbital mucormycosis cases, primarily affecting patients recovering from COVID-19 infection. The local health authorities have declared the current situation an epidemic. In this study, we assess the role of exenteration in preventing disease progression and improving survival in patients with rhino-orbital mucormycosis. METHODS: The patients undergoing exenteration were grouped into the exenteration arm and those denying exenteration were grouped into the nonexenteration arm. The patients were followed at 1 month and 3 months. The 6-month survival data were collected telephonically. Continuous data were presented as Mean ± SD/Median (IQR) depending on the normality distribution of data, whereas the frequency with percentages was used to present the categorical variables. Kaplan-Meier survival curves were created to estimate the difference in survival of patients with exenteration in rhino-orbital mucormycosis versus those without exenteration. RESULTS: A total of 14 patients were recruited for our study based on the inclusion and exclusion criteria. All the patients were qualified for exenteration; however, only eight patients underwent exenteration and six patients did not consent to exenteration. At the end of 3 months in the exenteration group, four (50%) patients died. Two patients died within a week of exenteration, whereas two patients died after 2 weeks of exenteration. The deaths in the first week were attributed to septic shock and the deaths happening beyond 2 weeks were attributed to severe meningitis. The Kaplan-Meier survival analysis showed the cumulative probability of being alive at 1 month in the exenteration arm to be 85%, and it decreased to 67% by 53 days and subsequently remained stable until the end of 3 months. CONCLUSION: The Kaplan-Meier survival analysis did not show a survival benefit of exenteration at 3 months and 6 months in COVID-associated rhino-orbital mucormycosis.