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Please note this is a comparison between Version 1 by Maria Panagiota Almyroudi and Version 5 by Beatrix Zheng.
Mucormycosis is a rare infection caused the members of the order Mucorales. Its prevalence ranges from 0.005 to 1.7 per million people worldwide, while in India, it reaches 14 cases per 100,000 inhabitants . During the COVID-19 pandemic, a surge in mucormycosis cases has been observed, especially in India, where the Government of India portal reported 47,508 cases from 5 May 2021 to 3 August 2021. Characteristically, Samir Joshi et al. reported 160 cases of COVID-19-associated mucormycosis (CAM) from April to May 2021 in the Ear, Nose, Throat Department of BJGMC-SGH hospital in India, compared with 3–8 cases of mucormycosis detected each year from 2016 to 2020.
- mucorales
- invasive fungal infections
- SARS-CoV-2
1. Clinical Presentation
CAM was diagnosed after a median of 17.4 days (Q1:14.4, Q3:21.8, IQR 7.5 days) post COVID-19 diagnosis (Table S1) but simultaneous manifestation with acute COVID-19 is also reported. Mucormycosis may be associated with neuroinflammation of the acute phase or be integrated in the post-COVID-19 syndrome [1][123]. However, the long period that is mediated between COVID-19 positivity and CAM diagnosis may actually reflect a delay in diagnosis, that may be associated with a higher mortality [2][33].
Mucormycosis most commonly affects the head and neck region. ROCM is the commonest form globally and was also the most frequent form associated with COVID-19. ROCM was diagnosed in 8082/8218 (98.3%) CAM patients and pulmonary infection in 98/8218 (1.2%), of whom 30.6% were in Europe. (Table 12). Mucormycosis of the gastrointestinal tract was found in 5/8218 (0.06%) CAM patients, cutaneous in 11/8218 (0.13%), disseminated in 11/8218 (0.13%) and renal in 1/8218 (0.01%) (Table 12). In Europe 3/40 (7.5%) of CAM patients had ROCM, 30/40 (75%) had pulmonary mucormycosis, 4/40 (10%) mucormycosis of the gastrointestinal tract and 3/40 (7.5%) disseminated (Figure 13).
Figure 13.
Clinical presentation of patients with CAM in total and in Europe.
Table 12. Incidence of CAM among hospitalized COVID-19 patients, type of infection, invasive or non-invasive mechanical ventilation, risk factors and all-cause mortality.
| Study | Incidence of CAM (%) | Type of Infection (%) |
Cerebral Involvement /ROCM pts, n (%) |
IMV or NIV n (%) |
DM (% of CAM pts) |
Steroids Intake (% of CAM pts) |
All-Cause Mortality (%) | |
|---|---|---|---|---|---|---|---|---|
| Said Ahmed WM et al. [3] | Said Ahmed WM et al. [29] | NA | Maxillary osteomyelitis | 0/14 (0%) | NA | 64.2% DM 35.7% with temporary post-COVID-19 hyperglycemia |
NA | NA |
| Murthy R et al. [4] | Murthy R et al. [30] | NA | RO | 0/111 (0%) | NA | NA | NA | NA |
| Walia S et al. [5] | Walia S et al. [31] | NA | SN (100%), O (51.85%), C (9.44%), Cu (1.85%), P (0.18%). | 51/529 (9.6%) | NA | 97.96% | 84.85% | 9.25% |
| Vare AA et al. [6] | Vare AA et al. [32] | 1.36% | ROCM | 3/67 (5%) | 18/67 (27%) | 90% | 84% | 34% |
| Fouad YA et al. [2] | Fouad YA et al. [33] | NA | O | 0/26 (0%) | NA | 96.2% | 76.9% | 46,2% |
| Soni K et al. [7] | Soni K et al. [34] | NA | ROCM | 29/145 (20%) | NA | 86.2% | 65% | 18% |
| Metwally MI et al. [8] | Metwally MI et al. [35] | NA | Head and neck | 8/63 (12.7%) | NA | 80.9% | 82.5% | 17.5% |
| Arora U et al. [9] | Arora U et al. [36] | NA | RS (29%), RO (47.3%), ROCM (14.5%), O (1.3%), RO/palatal (5.3%), Cu (0.6%), P (1.3%), D (0.6%) | 22/148 (14.9%) | NA | 92.1% | 65.8% | NA |
| Jindal G et al. [10] | Jindal G et al. [37] | NA | ROCM | 9/15 (60%) | NA | 100% | 80% | 6.6% |
| Syed-Abdul S et al. [11] | Syed-Abdul S et al. [38] | NA | NA | NA | NA | NA | NA | NA |
| Patel A et al. [12] | Patel A et al. [3] | NA | RO (96.5%), P (3.4%) | 0/28 (0%) | NA | NA | NA | NA |
| Pruthi H et al. [13] | Pruthi H et al. [39] | NA | P | NA | 0/5 (0%) | 100% | NA | 80% |
| Bansal SB et al. [14] | Bansal SB et al. [40] | 10.8% | RO (91%), P (9%) | NA | 0/11 (0%) | 64%, 36% developed transient hyperglycemia |
100% | 18.2% |
| Dulski TM et al. [15] | Dulski TM et al. [41] | NA | RO (10%), ROCM (30%), P (30%), D (20%), GI (10%) | 3/4 (75%) | 5/10 (50%) | 80% | 90% | 60% |
| Meshram HS et al. [16] | Meshram HS et al. [42] | 4.4% | ROCM (91.8%), P (8.2%) | 11/42 (26.2%) | 0/61 (0%) | 24.6% | 44% | 26.2% |
| Aggarwal SK et al. [17] | Aggarwal SK et al. [43] | NA | ROCM | 4/13 (30.8%) | NA | 92.3% | 92.3% | 15.4% |
| Kulkarni R et al. [18] | Kulkarni R et al. [44] | 2.1% (1 centre) | ROCM | 12/102 (11.8%) | NA | 81.6% | NA | 51%. |
| Choksi T et al. [19] | Choksi T et al. [45] | NA | ROCM | 6/73 (2%) | 17/73 (23.3%) | 74% | 98% | 36% |
| Kumar S et al. [20] | Kumar S et al. [46] | NA | ROCM | 60/287 (21%) | NA | 80% | NA | NA |
| Mehta R et al. [21] | Mehta R et al. [47] | NA | ROCM | 0/17 (0%) | NA | 100% | NA | NA |
| Panwar P et al. [22] | Panwar P et al. [48] | NA | ROCM | 0/7 (0%) | NA | 100% | 42.8% | 0% |
| Patel DD et al. [23] | Patel DD et al. [49] | NA | ROCM | 21/96 (21.9%) | 6/96 (6.3%) | 71.8% | 82.3% | NA |
| Vaid N et al. [24] | Vaid N et al. [50] | NA | ROCM | NA | NA | 33.8% | 100% | 10.7% |
| Goddanti N et al. [25] | Goddanti N et al. [51] | NA | ROCM | NA | NA | 95.7% | 79% | NA |
| Yadav T et al. [26] | Yadav T et al. [52] | NA | ROCM | 25/50 (50%) | NA | 86% | 44% | NA |
| Meshram VB et al. [27] | Meshram VB et al. [53] | NA | ROCM (90.9%), P (9%) | 3/10 (30%) | 0/11 (0%) | 54.5% | 100% | 27% |
| Zirpe K et al. [28] | Zirpe K et al. [54] | NA | ROCM | 20/84 (23.8%) | NA | 64.3% | 83.3% | 15.5% |
| Alloush TK et al. [29] | Alloush TK et al. [55] | NA | ROCM | 9/14 (64.2%) | 0/14 (0%) | 92.8% | NA | 21.4% |
| Pal P et al. [30] | Pal P et al. [56] | NA | ROCM | 3/10 (30%) | ΝA | 70% | 80% | 30% |
| Danion F et al. [31] | Danion F et al. [57] | NA | P(53%), GI (18%), ROCM (12%), D (18%) | NA | 13/17 (76.5%) | 47% | 76.5% | 88% |
| Nehara HR et al. [32] | Nehara HR et al. [58] | NA | ROCM | 18/105 (17.1%) | NA | 78.1% | 66.3% | 19.05% |
| Pandiar D et al. [33] | Pandiar D et al. [59] | NA | Oral | 0/12 (0%) | NA | 66,7% | NA | NA |
| Kumar S et al. [34] | Kumar S et al. [60] | NA | NA | NA | 0/55 (0%) | 83.6% | 98.2% | 16% |
| Bilgic A et al. [35] | Bilgic A et al. [61] | 2.5% | ROCM | NA | 6/38 (16%) | 50% | 100% | 5% |
| Guemas E et al. [36] | Guemas E et al. [62] | 7.1% | P | NA | NA | 20% | 90% | 50% |
| Kumar SG et al. [37] | Kumar SG et al. [63] | NA | ROCM | 44/101 (43.6%) | NA | 94% | 80.1% | 17.8% |
| Mani S et al. [38] | Mani S et al. [64] | NA | ROCM | 4/89 (4.5%) | NA | 96% | 92% | 3.4% |
| Dravid A et al. [39] | Dravid A et al. [65] | NA | ROCM (98.3%), D (1.7%) | 26/58 (44.8%) | 3/59 (5.1%) | 89.8% | 100% | 25.4% |
| Naruka S et al. [40] | Naruka S et al. [66] | NA | ROCM | 9/79 (11.4%) | NA | 100% | NA | 18.18% |
| Jain K et al. [41] | Jain K et al. [67] | NA | ROCM | 3/95 (3.2%) | NA | 77% | 100% | 5.2% |
| Bhanuprasad K et al. [42] | Bhanuprasad K et al. [68] | NA | ROCM | 39 (29.5%) | 3/132 (2.3%) | 97.7% | 55.3% | 9.8% |
| Desai EJ et al. [43] | Desai EJ et al. [69] | NA | ROCM | 0/100 (0%) | NA | 80% | NA | 20% |
| Nasir\n et al. [44] | Nasir\n et al. [70] | 0.35% | P (60%), ROCM (40%) | 4/4 (100%) | 3/10 (30%) | 70% | 80% | 70% |
| Gupta \s et al. [45] | Gupta \s et al. [71] | NA | ROCM | 4/56 (7.1%) | NA | 85% | 66% | 16% |
| Joshi S et al. [46] | Joshi S et al. [4] | NA | ROCM | 22/178 (12.4%) | 5/178 (2.8%) | 74.2% | 52.8% | 15% |
| Pradhan P et al. [47] | Pradhan P et al. [72] | NA | ROCM | 10/46 (21.7%) | NA | 95.65% | 89.1% | 19.5% |
| Mehta RNM et al. [48] | Mehta RNM et al. [73] | NA | ROCM | 33/215 (15.3%) | NA | 91% | 88% | 12.1% |
| Riad A et al. [49] | Riad A et al. [74] | NA | ROCM | 7/7 (100%) | NA | 85.7% | 100% | 0% |
| Guzmán-Castro S et al. [50] | Guzmán-Castro S et al. [75] | 0.04% | ROCM (83.3%), P(16.6%) | 5/5 (100%) | 2/6 (33.3%) | 83.3% | 100% | 83.3% |
| Seidel D et al. [51] | Seidel D et al. [76] | 2 centres: 0.67%, 0.58% ICU: 1.47%, 1.78% |
P(84.6%), ROCM (7.7%), GI (7.7%) | 1/1 (100%) | 11/13 (84.6%) | 23.07% | 84.6% | 53.8% |
| Gupta R et al. [52] | Gupta R et al. [77] | NA | ROCM | 25/115 (21.7%) | 13/115 (11.3%) | 85.2% | 100% | 21.7% |
| Alfishawy M et al. [53] | Alfishawy M et al. [78] | NA | ROCM (95.2%), P (4.8%) | 5/20 (25%) | NA | 90% | 100% | 33.3% |
| Dave TV et al. [54] | Dave TV et al. [79] | NA | ROCM | 19/58 (33%) | NA | 74% | NA | 34% |
| Selarka L et al. [55] | Selarka L et al. [80] | 1.8% | ROCM | 9/47 (19.1%) | 20/47 (42.6%) | 76.6% | 100% | 23.4% |
| Avatef Fazeli M et al. [56] | Avatef Fazeli M et al. [81] | NA | ROCM | 0/12 (0%) | 1/12 (8.3%) | 83.33% | 75% | 66.7% |
| Mishra Y et al. [57] | Mishra Y et al. [82] | 3.36% | ROCM | 0/32 (0%) | NA | 87.5% | 93% | 12.5% |
| Sen M et al. [58] | Sen M et al. [83] | NA | ROCM | 539/2826 (19.1%) | 114/1602 (7.1) | 78% | 87% | 14% |
| Pakdel F et al. [59] | Pakdel F et al. [84] | NA | ROCM | 7/15 (46%) | 1/15 (6.7%) | 86% | 46.6% | 47% |
| Y M. Reddy et al. [60] | Y M. Reddy et al. [85] | NA | RO | 0/6 (0%) | NA | 100% | 66.7% | 100% |
| R. Arora et al. [61] | R. Arora et al. [86] | NA | ROCM | 6/60 (10%) | NA | 98.3% | 63.3% | NA |
| D.P Gupta et al. [62] | D.P Gupta et al. [87] | NA | ROCM | NA | NA | 100% | NA | 5.7% |
| M.Gautam et al. [63] | M.Gautam et al. [88] | NA | ROCM | NA | NA | 100% | 66.7% | 0% |
| R.M.Mehta et al. [64] | R.M.Mehta et al. [89] | NA | P | NA | 4/5 (80%) | 80% | 100% | 80% |
| Y.M.Reddy et al. [65] | Y.M.Reddy et al. [90] | NA | ROCM | NA | NA | 100% | 80.6% | 35.5% |
| S.P.Singh et al. [66] | S.P.Singh et al. [91] | NA | RO | 0/6 (0%) | 0/6 (0%) | 100% | 66.7% | 16.7% |
| M.Hada et al. [67] | M.Hada et al. [92] | NA | ROCM | 54/270 (20%) | NA | 92.2% | 72% | NA |
| M. Kumar H et al. [68] | M. Kumar H et al. [93] | NA | ROCM (85.7%), P (14.3%) | 15/24 (62.5%) | 6/28 (21.4%) | 75% | 70.4% | 73.9% |
| S. Bhandari et al. [69] | S. Bhandari et al. [94] | NA | NA | NA | NA | 86.8% | 84.3% | NA |
| M Chouhan et al. [70] | M Chouhan et al. [95] | NA | ROCM | 9/41 (21.9%) | NA | 97.6% | 87.8% | 9.8% |
| Y. Singh et al. [71] | Y. Singh et al. [96] | NA | ROCM (92.3%), P (7.7%) | 2/12 (16.7%) | 10/13 (76.9%) | 61.5% | 84.6% | 69.2% |
| S M Desai et al. [72] | S M Desai et al. [97] | NA | ROCM | 3/50 (6%) | NA | 82% | 84% | 30% |
| A. Kumari et al. [73] | A. Kumari et al. [98] | NA | ROCM | 4/20 (20%) | NA | 80% | 80% | 30% |
| S. Mitra et al. [74] | S. Mitra et al. [99] | NA | ROCM | NA | NA | 100% | 78.1% | NA |
| A Ramaswami et al. [75] | A Ramaswami et al. [100] | NA | ROCM | 17/70 (24.3%) | NA | 70% | 70% | NA |
| A.R. Joshi et al. [76] | A.R. Joshi et al. [101] | NA | ROCM | 7/25 (28%) | 12/25 (48%) | 88% | 100% | 56% |
| A. Patel et al. [77] | A. Patel et al. [102] | 7 centers: 0.27% (general wards) | ROCM (86.1%), P (8.6%), renal (0.5%), other (e.g., Cu, GI) (2.7%), D (2.1%) | 44/161 (27.3%) | NA | 60.4% | 78.1% | 44.1% |
| S Sharma et al. [78] | S Sharma et al. [103] | NA | ROCM | 2/23 (8.7%) | NA | 91.3% | 100% | NA |
| R. Kant et al. [79] | R. Kant et al. [104] | NA | ROCM (96%), P (4%) | 11/96 (11.5%) | NA | 95% | 81% | 13% |
| C. Eker et al. [80] | C. Eker et al. [105] | NA | ROCM | 9/15 (60%) | NA | 100% | NA | 33.3% |
| A.K. Pandit et al. [81] | A.K. Pandit et al. [106] | NA | ROCM | 30/56 (53.6%) | NA | 85.7% | 53.6% | 30.6% |
| S.F. Youssif et al. [82] | S.F. Youssif et al. [107] | 7.6% | ROCM | 32/33 (97%) | NA | 63.6% | NA | 90.9% |
| A. Sekaran, et al. [83] | A. Sekaran, et al. [108] | NA | ROCM | 6/30 (20%) | 8/30 (26.7%) | 100% | 90% | 16.7% |
| R. R. Shabana et al. [84] | R. R. Shabana et al. [109] | NA | ROCM | 4/30 (13.3%) | 1/30 (3.3%) | 90% | 66.6% | 20% |
| A. K Patel et al. [85] | A. K Patel et al. [110] | NA | ROCM (92.2%), P (7.8%) | 5/59 (8.5%) | NA | 75% | 90.6% | 4.7% |
| H. D.D. Martins et al. [86] | H. D.D. Martins et al. [111] | NA | ROCM | 0/6 (0%) | NA | 83.3% | NA | 16.7% |
| S. Iqtadar et al. [87] | S. Iqtadar et al. [112] | NA | ROCM | NA | 0/7 (0%) | 71.4% | 100% | 14.3% |
| A. Al Balushi et al. [88] | A. Al Balushi et al. [113] | NA | ROCM | 3/10 (30%) | 6/10 (60%) | 100% | 30% | 60% |
| R. Soman et al. [89] | R. Soman et al. [114] | NA | ROCM (78.6%), P (21.4%) | 5/22 (22.7%) | NA | NA | NA | 25% |
C: Cerebral, Cu: Cutaneous, DM: Diabetes Mellitus, D: Disseminated, GI: gastrointestinal, IMV: Invasive Mechanical Ventilation, NA: Not Available, NIV: Non-invasive ventilation, O: Orbital, P: Pulmonary, RO: Rhino Orbital, ROCM: Rhino-Orbital-Cerebral Mucormycosis, RS: Rhino-sinus, SN: Sinonasal.
Clinical manifestations of head and neck mucormycosis include headache, loosening of teeth, black necrotic turbinate, facial pain, facial palsy, peri-orbital or facial swelling, skin induration and blackish discoloration [8][35]. Symptoms attributed to nasal and oral cavity invasion include epistaxis, bloody nasal discharge and palate destruction. Orbital extension may lead to destruction of the ophthalmic artery and optic nerves resulting in ptosis of the eyelid, proptosis, vision disturbances and blindness. In a large retrospective study from India, 519/2716 (19%) patients with CAM presented with vision loss [58][83]. Cavernous sinus involvement occurs due to extension from the orbit and manifests as diplopia and ophthalmoplegia [90][8].
Cerebral involvement was noted in 1400/7388 (18.9%) patients with COVID-19 associated ROCM, reported in 72 studies (Table 2). Cerebral involvement may manifest as cavernous sinus thrombosis, fungal abscess, meningitis and cerebrovascular disease [48][73]. Rahul Kulkarni et al. noted that 45/49 (91.8%) of patients with cerebral involvement presented with ischemic stroke, which concerned large artery infracts, followed by intracranial hemorrhage in 3/49 (6.1%) and sub-arachnoid hemorrhage in 1/49 (2.0%) [18][44].
Ninety-eight patients with pulmonary mucormycosis are described in the literature (57 in India, 30 in Europe, 6 in Pakistan, 3 in USA, 1 in Egypt and 1 in Mexico) (Table S3). Ten studies contained data on ventilatory support, with invasive or non-invasive mechanical ventilation reported in 26/45 (57.8%) of patients with COVID-19-associated pulmonary mucormycosis. In 7 studies where CAPA was sought, 19/43 (44.2%) patients with pulmonary mucormycosis were found with positive microbiological testing for Aspergillus. Symptoms of pulmonary mucormycosis in non-ventilated patients include fever, dyspnea, cough, chest pain and hemoptysis [91][124]. Pruthi et al. reported five cases of pulmonary mucormycosis associated with COVID-19 that were complicated by pulmonary artery pseudoaneurysm [13][39]. In mechanically ventilated patients, identification of an agent of mucormycosis from respiratory specimens in combination with compatible radiographic findings support the diagnosis.
Symptoms of mucormycosis of the gastrointestinal tract are non-specific and consist of abdominal pain and distension, diarrhea and gastrointestinal bleed [91][124], while disseminated mucormycosis may affect any organ, but mainly the brain and lungs, and is a result of bloodstream invasion in severely immunocompromised patients [91][124].
2. Diagnosis
Early recognition of CAM is crucial, as delay in therapy is associated with higher mortality [16][42]. A high index of suspicion should be maintained when clinical symptoms and radiological features appear in a patient with predisposing factors. According to criteria proposed by the European Confederation of Medical Mycology and the Mycoses Study Group Education and Research Consortium [92][6], the diagnosis of mucormycosis is based on clinical and imaging characteristics and confirmed with direct microscopy, histopathologic analysis and culture of samples obtained with biopsy.
Diagnosis is challenging, as appropriate specimens are obtained through invasive procedures and specific stains are needed to identify Mucorales. Direct microscopy with potassium hydroxide (KOH) mount is usually used for the rapid diagnosis of mucormycosis, as results are delayed with culture and histopathology. Direct microscopy reveals wide, non-septate, ribbon-like hyaline hyphae, with irregular right-angled branching that are characteristic of Mucorales [93][125]. Ιnfarcts, angioinvasion and perineural invasion are usually present in the histological analysis. Preceding antifungal therapy may alter morphological characteristics of the fungus, while specimens’ processing must be carefully undertaken to keep hyphae intact [94][2]. Even when fungal hyphae are recognized in histopathological analysis, cultures may be negative in 50% of cases, due to the fragility of fungal hyphae [93][125]. Characteristically, among 2175 patients with CAM, direct microscopy with KOH/calcofluor white was performed in 89% (1931), and culture in 19% (432), of cases [58][83].
Molecular techniques are promising, as rapid detection is needed and cultures are time-consuming and may be false-negative [91][124]. However, results should be cautiously evaluated due to ubiquitous nature of Mucorales. PCR was performed in five studies in the literature (two French, two from India and one from Egypt) and concerned 174 patients, of which 31 were positive (Table S4). In the French study [31][57], PCR was positive in 15/17 (88%) patients with CAM in serum (n = 14), BAL (n = 7), tissues (n = 3) and peritoneal fluid (n = 1) [31][57]. It is of interest that, in another French study [36][62], Mucorales was detected with PCR in respiratory samples of 10 COVID-19 patients, of which 80% simultaneously tested positive for Aspergillus. This cluster of cases was possibly attributed to environmental exposure, due to construction work near the hospital [36][62].
Few studies in the literature report on the species isolated, reflecting the difficulties encountered with culture-based identification and the infrequent use of PCR. Rhizopus sp. were the most common species isolated (Table S3). In a study including 203 cases of mucormycosis with positive cultures during the second wave of the pandemic in India, Rhizopus oryzae, followed by R. microspores, were most frequently identified [95][126].
Mixed infections with Aspergillus and Candida are detected both in pulmonary and rhino-orbital-cerebral form. Eighteen studies in the literature (12 from India, 3 from Europe, 2 from Pakistan and 1 from Egypt) refer to Aspergillus possible co-infection, with Aspergillus being isolated in 89/863 (10.3%) CAM patients (Table S4). Danion et al., reported 5 mixed fungal infections with Aspergillus in 17 (29%) CAM cases, of which 2 exhibited pulmonary involvement, 1 ROCM, 1 disseminated and 1 GI disease. All patients were mechanically ventilated and COVID-19-associated pulmonary aspergillosis (CAPA) was diagnosed at a median of 2 days before CAM. Four out of five patients with CAM and CAPA received L-Amphotericin B (one was diagnosed after death) and 5/5 died [31][57]. In Toulouse, France, eight cases of concomitant infection with Mucor and Aspergillus were detected in the ICU and were attributed to construction work that was undertaken near the hospital. All patients had pulmonary involvement, 3/8 were treated with L-Amphotericin B, 4/8 with a combination of L-Amphotericin B and Posaconazole and/or isavuconazole and 1/8 with isavuconazole. Four out of eight (50%) patients died [36][62]. Aspergillus fumigatus, Aspergillus niger and Aspergillus nidulans have been isolated [44][70], while mixed mold infections with Candida are also described in the literature [40][41][66,67]. Nidhya Ganesan et al. reported that among 60 biopsy samples from suspected rhino-maxillary/rhino-orbital mucormycosis post COVID-19, mucorales was isolated in 58 (96.67%) samples, aspergillus along with mucorales in 12 (20%) and a combination of mucorales and candida in 8 (13.33%) [96][24].
Neither 1,3-beta-D-glucan assay and galactomannan are positive in mucormycosis but can aid in the diagnosis of invasive pulmonary aspergillosis, which is recognized as a severe superinfection of COVID-19 pneumonia resulting in higher mortality. A positive serum or BAL galactomannan in a patient with compatible clinical presentation and imaging findings is indicative of invasive aspergillosis [97][127]. BAL galactomannan was measured in the study of R.H. Mehta et al. and was found positive (≥1) in 4/5 cases of COVID-19-associated pulmonary mucormycosis. In two cases, Aspergillus fumigatus was isolated in fungal culture, while in three cases, Aspergillus was identified in histopathological analysis [64][89]. Ultimately, mixed infection should be actively searched and isavuconazole is a potential empirical choice if mixed infection is suspected.
