CT Findings of COVID-19–associated Pulmonary Mucormycosis: A Case Series and Literature Review

Abstract

Introduction

There has been an unprecedented spike in COVID-19–associated mucormycosis (CAM), with most patients showing rhino-orbital involvement, whereas limited data are available on COVID-19–associated pulmonary mucormycosis (CAPM). Pulmonary mucormycosis is rare and has a high mortality rate (1). COVID-19 pneumonia makes it further challenging to identify pulmonary mucormycosis at radiologic imaging. Herein, we describe the imaging findings of three confirmed cases of CAPM and supplement it with a systematic review of the literature.

Materials and Methods

In this retrospective study (approved by the institute ethics committee), we describe the imaging and clinical features of three microbiologically confirmed cases of CAPM. We performed a systematic review of the PubMed and Embase databases, using the search terms (“COVID” OR “SARS-CoV” OR “coronavirus”) AND (mucor* OR “zygomycosis”) until June 14th, 2021, to identify published cases of CAPM (diagnosed as per current recommendations) (2). We included them for analysis if individual patient and imaging data were provided.

Results

At our center, we diagnosed three cases of CAPM (Figure). Two of the three patients had no risk factor other than COVID-19. One case was of a man with diabetes with both rhino-orbital involvement and pulmonary mucormycosis. Two patients survived. We identified 180 cases of CAM in the literature during the review period and included only those 88 cases (14 CAPM and 74 nonpulmonary CAM) for which individual patient details were available (3–28). Of the 14 CAPM cases reported (three from the United States, two from the United Kingdom, three from the Netherlands, two from India, and one each from Italy, Austria, Chile, and France) (12,29–38), CT details were unavailable in one (12). After exclusions, we report the CT features of these 13 cases along with the three index cases reported by us (n = 16) (Table).

Patient 1: A 45-year-old diabetic man, positive for SARS-CoV-2, presented with loss of vision in left eye and facial swelling on the 12th day of illness. (A) Coronal CT section of paranasal sinuses and orbits shows soft tissue in the left maxillary sinus (asterisk) causing blockage of osteomeatal complex. There is fat stranding in left orbit with increased bulk of left medial and inferior rectus muscles (arrows) suggesting orbital extension. (B) Axial CT chest sections show thick-walled cavitatory lesion in right lower lobe (black arrow) and large area of consolidation in left upper lobe (white arrow). Patchy ground-glass opacities (GGOs) with septal thickening were noted in bilateral lungs (dashed black arrow) consistent with underlying COVID-19 pneumonia. (C) Lactophenol cotton blue mount (10×) of culture of endotracheal aspirate depicted long smooth-walled sporangiophores, globose sporangia (black arrows), and subglobose to ellipsoidal sporangiospores with striations suggesting it to be Rhizopus arrhizus. Patient died 25 days after the onset of illness due to massive hemoptysis.

Patient 2: A 36-year-old woman, positive for COVID-19 infection, had persistent hypoxia despite being on oxygen therapy and systemic corticosteroids. Chest CT was performed on day 24 of illness. (D,E) Axial sections of CT (lung window and corresponding mediastinal window) show multiple thin- to thick-walled cavities (black arrows in D; white arrows in E) in bilateral lungs, many of them showing air-fluid levels. Loculated right hydropneumothorax (⋆) with left pleural effusion was seen. (F) KOH wet mount preparation from endotracheal aspirate revealed aseptate, ribbon-like fungal hyphae (40×). Patient was started on amphotericin B and subsequently improved.

Patient 3: A 45-year-man with no known comorbid illness, positive for SARS-CoV-2, underwent chest CT on day 25 of illness, due to persistent fever and dyspnea. (G) Coronal section of chest CT shows patchy GGOs and consolidation with septal thickening in right lung (curved arrows) consistent with underlying COVID-19 pneumonia. Note the mild right pneumothorax (dashed arrow). (H) Coronal CT chest section performed 7 days later shows cavitatory lesion in left lung with few septae within. Pneumothorax and COVID-19 pneumonia changes have resolved. (I) Direct microscopy (KOH mount) of endotracheal aspirate (40×) shows aseptate, ribbon-like broad hyphae. Patient improved on amphotericin B treatment and was discharged.

Clinical Characteristics, Imaging, Treatment, and Outcome of CAPM versus CAM

The most frequent CT findings were consolidation and cavitation seen in 11 (69%) patients. Pleural effusion was seen in seven (47%) patients, pneumothorax and nodules in three (19%) patients, and the “reverse halo” and pulmonary embolism were seen in two (13%) patients.

We compared CAPM with nonpulmonary CAM identified from our review (Table). The risk factor profile was significantly different in both groups. No risk factors other than COVID-19 and its treatment were identified in 47% of CAPM. Although diabetes mellitus was common in CAPM (29%), it was significantly less than in nonpulmonary CAM (82%). Patients with CAPM were more often undergoing mechanical ventilation than were patients with nonpulmonary CAM (71% vs 40%; P = .02). CAPM was diagnosed after a median of 20 days (range, 9–29 days) after the onset of COVID-19 symptoms. Surgery was performed only in 12% of patients with CAPM, whereas 82% of patients with nonpulmonary CAM (mostly rhino-orbital) underwent surgery. Amphotericin-B was not instituted in 18% and 3% of the CAPM and nonpulmonary CAM cases, respectively (P = .02). CAPM had higher mortality than did nonpulmonary CAM cases (71% vs 42%; P = .03). Notably, three CAPM cases were not suspected antemortem (30,34,38).

Discussion

Mucormycosis has been shown to occur in fewer than 1% of hospitalized patients with COVID-19, and pulmonary mucormycosis accounts for 9% of CAM (39,40). Although CT findings of pulmonary mucormycosis have been described previously (41,42), CAPM has not been systematically explored. In a study reporting pulmonary mucormycosis among hematologic malignancies (before the COVID-19 pandemic), consolidation (55%), and nodules (35%) were the primary initial findings, whereas central necrosis, cavity, and air crescent sign appeared later (41). We found consolidation and cavitation to be the predominant findings (69%) in our study, possibly reflecting delayed identification of cases of CAPM. The imaging findings of CAPM may overlap with COVID-19–associated pulmonary aspergillosis and cavitating bacterial pneumonias, making the differentiation difficult. Sometimes even coinfections are seen (29,31).

There were few limitations in our study. We included only confirmed cases of CAPM and it may not reflect the entire spectrum, because many patients with high suspicion remain unproven or die before reaching the hospital. Second, we did not evaluate serial CT findings. Third, many published reports did not explicitly catalog the CT findings of CAPM. We summarized the data from a small number of patients with CAPM, and larger studies are required.

In conclusion, COVID-19–associated pulmonary mucormycosis (CAPM) has higher mortality than does nonpulmonary CAPM, and the most frequent CT findings of CAPM are consolidation and cavitation.