key: cord-0898216-tszsvk0e authors: Chowdhury, Melissa; Takata, Junko; Beegun, Issa; Burd, Chris; Tatla, Taranjit; Corrah, Tumena title: Image challenge: left sided facial swelling in a patient with COVID-19 date: 2021-12-08 journal: Clin Infect Pract DOI: 10.1016/j.clinpr.2021.100129 sha: 50c5f63be58fd7338e981b6b4c77e851e7c968d5 doc_id: 898216 cord_uid: tszsvk0e A 68-year-old man with diabetes presented with shortness of breath, left sided facial swelling, and nasal discharge. He had recently returned from India and PCR was positive for SARS-CoV-2 Delta variant. CT head and diffusion-weighted MRI sinuses were performed and the patient underwent endoscopic sinus surgery before being transferred to a specialist skull base centre. A 68-year-old man of Indian origin presented with a 3-day history of shortness of breath and headache after returning from Punjab, India. His past medical history included poorly controlled Type 2 diabetes (HbA1c on admission 139 mmol/mol, reference range 20-41 mmol/mol), chronic kidney disease, previous pulmonary tuberculosis, possible lung cancer that was still under investigation, and a tooth extraction a month ago in India. He had tested negative for COVID-19 prior to leaving India. On presentation, he had a heart rate of 128, respiratory rate of 34, blood pressure of 142/106, oxygen saturations 90% on 4L oxygen, and he was afebrile. He was in diabetic ketoacidosis with blood glucose of 40 mmol/L, ketones of 7 mmol/L, and pH 7.22. Initial investigations showed raised inflammatory markers (CRP 124.6 mg/L, reference range 0-5 mg/L; WBC 14.5 10^9/L, reference range 4.2-10.6 10^9/L; neutrophils 13.1 10^9/L, reference range 2.0-7.1 10^9/L; lymphocytes 0.6 10^9/L, reference range 1.1-3.6 10^9/L), acute kidney injury (urea 15.9 mmol/L, reference range 2.5-7.8 mmol/L, creatinine 144 umol/L, reference range 60-125 umol/L), raised D-dimer (7223 ng/mL FEU, reference range 0-275 ng/mL FEU), and bilateral infiltrates on the chest radiograph. He tested positive for SARS-CoV-2 Delta variant on the day of admission and was transferred to the high-dependency unit where he received dexamethasone, remdesevir, tocilizumab, and supplementary oxygen up to 60% FiO2. CT pulmonary angiography showed changes consistent with COVID-19 and a right pulmonary embolism, for which he was anticoagulated. On further questioning, he revealed a history of left sided facial swelling and left mucoid nasal discharge for approximately one month after his tooth extraction. On examination, there was swelling in the left maxillary area that was mildly tender, with no evidence of cellulitis, fluctuation or collection. There was mild swelling of the left eyelid, but it was painless with normal eye movements, acuity and pupillary reflexes. There was an upper left 6 th tooth extraction in the mouth with no palatal lesions. On flexible nasoendoscopy, there was evidence of left sided congestion, mucus discharge and septal deviation to the left. Superficial nasal swabs were taken and sent for bacterial and fungal culture. Initial CT head with contrast showed opacification of the maxillary antra, left ethmoid air cells, frontal sinuses, and sphenoid sinuses ( Figure 1 ). Following empirical therapy, he underwent endoscopic sinus surgery on day 14 involving left sided maxillary antrostomy, anterior and posterior ethmoidectomy, sphenoidotomy, and excision of the inferior turbinate ( Figure 2) . Given his recent travel to India, COVID-19 infection, and background of uncontrolled diabetes, mucormycosis infection was suspected. The diagnosis was confirmed on histology from the surgery, which showed fungal hyphae consistent with both Mucor and Aspergillus spp ( Figure 3 ), and superficial nasal swab cultures also grew Rhizopus species and Aspergillus flavus. Prior to surgery, he was empirically commenced on systemic liposomal amphotericin B (5mg/kg) on day 6, as well as betamethasone 0.1% and xylometazoline 0.1% nasal drops and saline nasal douches. The patient was transferred to our specialist infectious diseases unit on day 9. Due to the extent of disease following surgery, amphotericin B was increased to 7mg/kg and posaconazole 300mg was added. This was subsequently switched to isavuconazole 200mg, as the minimum inhibitory concentration of R. microsporus was 0.5 mg/L (sensitive) to amphotericin, 1 mg/L (sensitive) to isavuconazole, and 1 mg/L (intermediate) to posaconazole. Despite surgery and antifungal therapy his condition continued to progress. He developed chemosis, proptosis and complex ophthalmoplegia in the left eye and necrotic lesions in the upper hard palate. He also developed episodes of epistaxis, haemoptysis and melaena. Repeat MRI orbit and head with contrast on day 23 and CT skull base fine cut on day 24 showed progression of disease in the posterior soft tissues and orbital contents, bony erosive changes of the medial orbital wall, sphenoid septum and sphenoid posterior wall, and asymmetrical cortical erosion of the floor of the left middle cranial fossa and abnormal clivus marrow signal (Figures 4 & 5) . CT venogram showed no cerebral venous system involvement. To clear diseased tissue, he required aggressive open surgery to debride the soft and bony tissues of the left hemi-face. He was therefore transferred to a specialist skull base surgical centre on day 31 where he underwent an extended maxillectomy and skull base clearance on day 37. Intraoperative findings were of a necrosed left maxilla, pterygoid muscles and periorbita, as well as necrotic dead bone when drilling the bony floor of the left middle cranial fossa. The foramen rotundum was full of necrotic tissue. Unfortunately, the patient deteriorated from a COVID pneumonitis perspective and required invasive ventilation in intensive care, where he passed away from COVID pneumonitis on day 47 of his illness. Mucormycosis is a rare and serious fungal infection caused by moulds of the order Mucorales, with Rhizopus, Mucor and Rhizomucor the most commonly implicated genera in human infections. Whilst found throughout the environment, it particularly causes disease in those who are immunocompromised or with diabetes mellitus. (1) One of the most devastating manifestations is severe rhino-orbital-cerebral infection, as demonstrated in our case, and overall mortality ranges from 25 to 62 percent despite antimicrobials or surgical intervention. (2) It is therefore vital to have a high index of suspicion in those with suggestive signs or symptoms and initiate appropriate management promptly, including controlling risk factors such as hyperglycaemia and immunosuppression, along with use of antifungals such as amphotericin B, posaconazole or isavuconazole. Due to how rapidly mucormycosis can destroy tissue, urgent referral for aggressive surgical debridement is a crucial step. As demonstrated by our case, serial imaging with CT and diffusion-weighted MRI is vital to characterise soft tissue and bony spread in mucormycosis (3) , which in turn can aid prognostication and early referral to specialist centres. There is currently renewed interest in mucormycosis due to its association with COVID-19. An autopsy series of ten patients who died from COVID-19 found one case of disseminated mucormycosis, (4) and there have been descriptions of the link between COVID-19 infection and other fungal infections such as invasive aspergillosis. (5) In particular, there has been an explosion of cases in India in the current COVID-19 wave, with catastrophic consequences on the local health system infrastructure. (6) The relationship between COVID-19 and mucormycosis is at present poorly understood. (7, 8) In an Indian case series of 187 patients, COVID-19-related hypoxaemia and improper glucocorticoid use were independently associated with mucormycosis. (9) In India, there is widespread use of steroids for even mild cases, which may potentiate both an immunosuppressed state and poor diabetic control. COVID-19 itself may exacerbate hyperglycaemic states, with the link between COVID-19 and diabetic ketoacidosis being well described previously. (10) Furthermore, given that hospitals in India have been overwhelmed in this last wave of COVID-19, healthcare-associated mucormycosis remains a possibility, such as potentially contaminated ventilation systems. (11) In addition, there may be possible risks associated with particular variants -in particular, the Delta COVID-19 variant (B.1.617.1), currently the predominant strain in both India and the UK. (12) We present a case of COVID-19 infection and associated mucormycosis. Our case demonstrates the devastating consequences of this condition, along with the complicating effects of concomitant COVID-19 infection. As the UK enters a new phase of the COVID-19 pandemic, it is crucial for UK clinicians to remain vigilant of the possibility of the link between COVID-19 and mucormycosis to ensure life-saving treatment can be rapidly instituted for this incredibly aggressive disease. Zygomycosis: An emerging fungal infection with new options for management Epidemiology and outcome of zygomycosis: A review of 929 reported cases Magnetic resonance imaging in rhino-orbital-cerebral mucormycosis Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. The Lancet Microbe Epidemiology of invasive pulmonary aspergillosis among COVID-19 intubated patients: a prospective study Mucormycosis: time to address this deadly fungal infection. The Lancet Microbe The surge in Covid related mucormycosis When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis Early Release -Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations Outbreaks of Mucorales and the Species Involved Covid-19: Delta variant is now UK's most dominant strain and spreading through schools We gratefully acknowledge Dr Manjiri Deshmukh at the Department of Histopathology, Northwick Park Hospital, for helping to coordinate photographs of specimens; and Mr Peter Clarke and Miss Aphrodite Iacovidou at the Department of ENT Surgery, Charing Cross Hospital, for their valuable contributions to this case. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Verbal and written consent gained from subject of case report. None declared for all authors.