Genetic Manipulation in Mucorales and New Developments to Study Mucormycosis.

The study of the Mucoralean fungi physiology is a neglected field that the lack of effective genetic tools has hampered in the past. However, the emerging fungal infection caused by these fungi, known as mucormycosis, has prompted many researchers to study the pathogenic potential of Mucorales. The main reasons for this current attraction to study mucormycosis are its high lethality, the lack of effective antifungal drugs, and its recent increased incidence. The most contemporary example of the emergence character of mucormycosis is the epidemics declared in several Asian countries as a direct consequence of the COVID-19 pandemic. Fortunately, this pressure to understand mucormycosis and develop new treatment strategies has encouraged the blossoming of new genetic techniques and methodologies. This review describes the history of genetic manipulation in Mucorales, highlighting the development of methods and how they allowed the main genetic studies in these fungi. Moreover, we have emphasized the recent development of new genetic models to study mucormycosis, a landmark in the field that will configure future research related to this disease.

PULMONARY ARTERY PSEUDOANEURYSM (PAP) AND MASSIVE HEMOPTYSIS AS A COMPLICATION OF MUCORMYCOSIS AND COVID-19 PNEUMONIA

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: PAP is a rare entity that can occur secondary to infection, malignancy, or trauma. Mucormycosis in the setting of Covid-19 pneumonia has been increasingly recognized but PAP has only recently been reported in this setting. CASE PRESENTATION: A 44 year-old man with type 2 diabetes, non-ischemic cardiomyopathy, hypothyroidism, and ulcerative colitis presented with dyspnea and cough in July 2021. He was diagnosed with Covid-19 pneumonia and initially treated with molnupiravir. Eight days later he presented to the emergency room with worsening dyspnea, hypoxemia and diabetic ketoacidosis. He required 3L of oxygen and was intubated for airway protection. CT chest revealed mild bilateral patchy opacities and dexamethasone was started. Unfortunately, persistent fevers and worsening respiratory status ensued and repeat chest CT on hospital day (HD) 8 showed a new large left upper lobe (LUL) cavitary lesion. Cultures ultimately grew Rhizopus microsporus and he was started on amphotericin then isavuconazole after acute kidney injury developed. Dexamethasone was discontinued and interval imaging after ten days showed dramatic growth of the cavitary lesion (9 x 6 x 3 cm) with new extension through the chest wall, infiltrating the intercostal spaces and pectoralis muscle. Due to ventilator dependency a tracheostomy was performed on HD 24. Despite anti-fungal therapy the cavitary lesion persisted, with evidence of osseous destruction of the third and fourth ribs, as well as new fluid collections within the cavity and hilar extension. On HD 46 he was transferred to our institution for Thoracic Surgery and Interventional Radiology (IR) evaluations. Percutaneous drain placement followed by pneumonectomy vs. staged cavernostomy was considered;however, on HD 50, the patient suddenly developed massive hemoptysis. CTA of the chest showed a 1.6 x 1.5 cm PAP with active hemorrhage from the LUL anterior segmental artery with dispersion into the cavity. Urgent coil and glue embolization was successfully performed by IR. Ultimately, thoracic surgical intervention was deemed too high risk and thus he was medically managed with a regimen of isavuconazole, amphotericin, and terbinafine. Hemoptysis did not recur and he was eventually discharged from the hospital and liberated from both mechanical ventilation and tracheostomy. Chest CT 6 months from the initial diagnosis has shown stable to mildly decreased size of the cavitary lesion. DISCUSSION: This is the first case to our knowledge of PAP as a complication of Covid-19 and Mucor superinfection in the United States. Five cases of this combination have been recently reported in other countries. Risk factors for Mucor infection after Covid appear to be uncontrolled diabetes, DKA, and steroid administration. CONCLUSIONS: A high index of suspicion should be maintained in patients with these risk factors, as PAP can present as massive hemoptysis and is often fatal. Reference #1: Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries [ 2022 Jan 25]. Lancet Microbe. 2022;10.1016/S2666-5247(21)00237-8. doi:10.1016/S2666-5247(21)00237-8 Reference #2: Pruthi H, Muthu V, Bhujade H, et al. Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature. Mycopathologia. 2022;187(1):31-37. doi:10.1007/s11046-021-00610-9 Reference #3: Coffey MJ, Fantone J 3rd, Stirling MC, Lynch JP 3rd. Pseudoaneurysm of pulmonary artery in mucormycosis. Radiographic characteristics and management. Am Rev Respir Dis. 1992;145(6):1487-1490. doi:10.1164/ajrccm/145.6.1487 DISCLOSURES: No relevant relationships by Kevin Patel No relevant relationships by Clifford Sung

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.