Clinical Features and Treatment Progress of Invasive Mucormycosis in Patients with Hematological Malignancies.

The incidence rate of invasive mucormycosis (IM) in patients with hematological malignancies (HMs) is increasing year by year, ranging from 0.07% to 4.29%, and the mortality rate is mostly higher than 50%. With the ongoing pandemic of COVID-19, COVID-19-associated mucormycosis (CAM) also became a global health threat. Patients with high risk factors such as active HMs, relapsed/refractory leukemia, prolonged neutropenia may still develop breakthrough mucormycosis (BT-MCR) even under the prophylaxis of Mucorales-active antifungals, and such patients often have higher mortality. Rhizopus spp. is the most common genus associated with IM, followed by Mucor spp. and Lichtheimia spp. Pulmonary mucormycosis (PM) is the most common form of IM in patients with HMs, followed by rhino-orbital-cerebral mucormycosis (ROCM) and disseminated mucormycosis. The prognosis of IM patients with neutrophil recovery, localized IM and receiving early combined medical-surgical therapy is usually better. As for management of the disease, risk factors should be eliminated firstly. Liposome amphotericin B (L-AmB) combined with surgery is the initial treatment scheme of IM. Those who are intolerant to L-AmB can choose intravenous formulations or tablets of isavuconazole or posaconazole. Patients who are refractory to monotherapy can turn to combined antifungals therapy.

Gracin's Syndrome, a Rare Clinical Challenge in the Setting of Invasive Mucormycosis: A Systematic Review.

Garcin's Syndrome is a rare pathology involving multiple cranial nerves in the setting of invasive mucormycosis, usually in immunocompromised patients. Owing to its extremely high mortality rate, clinician should have a high suspicion for diagnosis. This article presents a rare case of Rhino-Orbito-Cerebral Mucormycosis with Garcin's syndrome in a 33-years old male along with a discussion of previously reported cases. The case is discussed in light of scant contemporary literature on the cited subject. A thorough search using the keywords Garcin's Syndrome, Invasive Mucormycosis, Rhino-orbital, Rhino-cerebral mucormycosis, was conducted on Pubmed/MEDLINE, Google scholar, LILACS, medRxiv and Google. A total of six reported cases found in international literature published between 2000 and 2020 were reviewed and analyzed. Garcin's Syndrome is associated with a high mortality rate. In our review, of the total seven patients, only three survived, bringing the collective mortality to 42.85%. Patients had multiple cranial nerve involvement leading to long term sequelae. Our case showed the unique finding of VIII nerve involvement. Early intervention helped in patient survival and better functional outcome. This literature review highlights the distinct clinical nature of the presentation of disease and the importance of prompt diagnosis and early management in the reversal of complications in an otherwise potentially fatal disease.

Estimation of Serum Levels of Heavy Metals in Patients with Chronic Invasive Fungal Rhinosinusitis Before the COVID-19 Era: A Pilot Study.

Objective: Various metals play role in the survival and pathogenesis of the invasive fungal disease. The objectives of this study were to compare the levels of heavy metals in patients with chronic invasive fungal rhinosinusitis (CIFR) and healthy controls, and to analyze their role in disease outcome. Methods: Twenty-three patients (15 with invasive mucormycosis and 8 with invasive aspergillosis, Group 1), and 14 healthy controls (Group 2) were recruited. Blood samples were collected from each group into ion-free tubes and analyzed for serum levels of Nickel (Ni), Copper (Cu), Zinc (Zn), Gallium (Ga), Arsenic (As), Selenium (Se), Rubidium (Rb), Strontium (Sr), Cadmium (Cd), and Lead (Pb). The final outcome of the patients during their hospital stay was categorized clinico-radiologically as improved or worsened, or death. Results: The levels of all metals were higher in Group 1 except for As and Pb. However, the differences in Cu (p=0.0026), Ga (p=0.002), Cd (p=0.0027), and Pb (p=0.0075) levels were significant. Higher levels of Zn (p=0.009), Se (p=0.020), and Rb (p=0.016) were seen in the invasive aspergillosis subgroup. Although Zn (p=0.035), As (p=0.022), and Sr (p=0.002) levels were higher in patients with improved outcome, subgroup analysis showed no differences. Conclusion: The levels of some heavy metals in CIFR significantly differ from those of the general population and also vary with the type of the disease and its outcome. These levels may not have a direct effect on the outcome of the patient, but they do play a role in the pathogenesis of the invading fungus.

Disseminated mucormycosis in a patient with severe COVID-19 on venovenous extracorporeal membrane oxygenation: A case report.

Background: Since the global outbreak of coronavirus disease 2019 (COVID-19), there have been several reports of mucormycosis as a secondary complication. However, the disseminated type of mucormycosis is extremely rare. Case: A 58-year-old male patient with COVID-19 started receiving venovenous extracorporeal membrane oxygenation because of severe respiratory failure. During hospitalization, intra-abdominal hemorrhage occurred and an emergency laparotomy was performed. Subsequently, the patient suffered septic shock, and part of the small intestines and the abdominal wall became necrotic. Finally, the patient died. At autopsy, he was diagnosed with disseminated mucormycosis. Conclusion: Disseminated mucormycosis should be considered in patients with COVID-19 with refractory sepsis unresponsive to broad-spectrum antimicrobial therapy.

Epidemic in pandemic: Fungal sinusitis in COVID-19.

Objective: To describe the clinical pattern of invasive fungal sinusitis in COVID-19 and post-COVID-19 cases. Methods: All patients affected by COVID-19 or having a history of COVID-19 infection with an invasive fungal lesion (mucormycosis/aspergillosis) of the paranasal sinuses, orbit, palate, brain, lung, skin/cheek, and dental has been evaluated for possible description in tertiary care hospital in May 2021. Results: Twenty-four patients presented with clinical signs and symptoms of fungal infection with a history of COVID-19. Paranasal sinuses were involved in all patients. Palatal involvement was seen in seven cases. Intraorbital extension was seen in 13 cases. Intracerebral involvement was seen in three cases. Comorbid type 2 diabetes was seen in 20 patients. The use of steroids was noticed in 16 cases. Our observation revealed that uncontrolled diabetes, overuse of steroids, increased ferritin levels, and low hemoglobin percentage are the main factors aggravating mucormycosis.

New-onset hyperglycaemia and prolonged systemic corticosteroids therapy in mild COVID-19 patients as major risk factors for invasive mucormycosis: a preliminary study.

Background and Purpose: Rapid surge of invasive mucormycosis has surprised the Indian healthcare system amidst the coronavirus disease-19 (COVID-19) pandemic. Hence, there is an urgent need to find the risk factors for the sudden rise in cases of invasive mucormycosis among COVID-19 patients. This study aimed to find crucial risk factors for the sudden surge of invasive mucormycosis in India. Materials and Methods: This case-control study included 77 cases of COVID-19 associated mucormycosis (CAM) who matched the controls (45 controls) in terms of age , gender, and COVID-19 disease severity. The control group included subjects that matched controls without mucormycosis confirmed by reverse transcription-polymerase chain reaction at our tertiary care center during April-May 2021. Probable predisposing factors, such as duration of diabetes mellitus (DM), history of recent hospitalization, duration of hospital stay, mode of the received oxygen supplementation, and use of steroids, zinc, vitamin c, and any other specific drugs were collected and compared between the two groups. Moreover, the laboratory parameters, like glycated hemoglobin (HbA1c), highly sensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were analyzed to find out the significant association with CAM. Results: DM (Odds ratio=7.7, 95% CI 3.30-18.12; P=<0.0001) and high glycated hemoglobin level (HbA1c>7.5 gm %) (odds ratio=6.2, 95% CI 1.4-26.7; P=0.014) were significant risk factors for the development of invasive mucormycosis among the COVID-19 cases. A higher number of mild COVID-19 cases developed CAM, compared to the moderate to severe cases (59.7% vs 40.3%). Use of systemic corticosteroids (odd ratio=5 with 95% CI 1.5-16.9; P=0.007) was found to be a risk factor for invasive mucormycosis only in mild COVID-19 cases. Use of oxygen, zinc, and vitamin C supplementation, and proprietary medicine did not lead to a significant risk of invasive mucormycosis in cases, compared to controls. Cases with invasive mucormycosis had a higher level of inflammatory markers (hs-CRP and ESR, P=<0.001 and 0.002, respectively), compared to the controls. Conclusion: Uncontrolled and new-onset DM and the use of systemic corticosteroids in mild cases were significantly associated with a higher risk of invasive mucormycosis in COVID-19 cases. There should be a strong recommendation against the use of systemic corticosteroids in mild COVID-19 cases.

Outbreak of Mucormycosis in Coronavirus Disease Patients, Pune, India.

We provide an overview of the epidemiology and clinical course of mucormycosis in the coronavirus disease (COVID-19) pandemic era. We conducted a retrospective chart review of 178 patients with clinical or diagnostic, endoscopically or histopathologically confirmed rhino-sino-orbital or cerebral mucormycosis after COVID-19 treatment during the second wave of COVID-19 in Pune, India. Median time to symptom onset from COVID-19 detection was 28 days. Moderate or severe COVID-19 was seen in 73% of patients and diabetes in 74.2%. A total of 52.8% received steroids. Eschar over or inside the nose was seen in 75%, but baseline clinical and laboratory parameters were mostly unremarkable. Bone penetration was present in ≈90% of cases, 30% had soft-tissue swelling of the pterygopalatine fossa and 7% had cavernous sinus thrombosis, and 60% had multifocal mucormycosis. Of the 178 study cases, 151 (85%) underwent surgical debridement. Twenty-six (15%) died, and 16 (62%) of those had multifocal mucormycosis.

Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis.

INTRODUCTION: Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and invasive mucormycosis (IM) are two of the most common mold infections. A better understanding of patient comorbidities and risk factors that predispose IMI may help clinicians to refine the difficult diagnostic and treatment process. METHODS: A systematic literature review (SLR) was conducted (January 2008-October 2019) for studies reporting comorbidities/risk factors of patients with IA or IM (Phase I), followed by an analysis on the Optum® US EHR database of prominent risk factor cohorts based on SLR findings and expert opinion (Phase II). From the four identified patient cohorts: 1) patients undergoing solid organ transplant (SOT) and patients with 2) hematologic cancers, 3) diabetes, or 4) lung disease, rates of IA, IM, or concurrent IA and IM; patient comorbidities; and Charlson Comorbidity Index (CCI) scores were reported. RESULTS: The SLR included 88 studies, and 46 were used to select comorbidities/risk factors cohorts in IA and IM patients. The most important comorbidities/risk factors in IA and IM patients were diabetes, lung disease, hematological malignances, and SOT. In the Optum database (N=101,340,454 patients), IA rates were highest in lung transplant (10.81%) patients and IM rates were highest in intestine transplant (0.83%) patients, lung transplant (0.43%), and hematopoietic stem cell transplant (0.49%). CCI scores were elevated in all mold infection groups compared to the total Optum cohort. CONCLUSION: The current study describes patient comorbidity and risk factors associated with IA and IM. These data can be used to refine clinical decision-making regarding when to suspect mold infections. Future research should focus on identifying whether patients respond differently to various antifungal treatments to determine if strategic recommendations should be made for certain patient groups.

Case series of four secondary mucormycosis infections in COVID-19 patients, the Netherlands, December 2020 to May 2021.

We describe four secondary fungal infections caused by Mucorales species in COVID-19 patients. Three COVID-19 associated mucormycosis (CAM) occurred in ICU, one outside ICU. All were men aged > 50 years, three died. Clinical presentations included pulmonary, rhino-orbital cerebral and disseminated infection. Infections occurred in patients with and without diabetes mellitus. CAM is an emerging disease and our observations underscore the need to be aware of invasive mucormycosis, including in COVID-19 patients without (poorly controlled) diabetes mellitus and outside ICU.