Mucormycosis co-infection in COVID-19 patients: An update
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Abdullah S. Alkhamiss
Abstract
Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients’ co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.
1 Introduction
Mucormycosis (MCM) is described as a rare invasive fungal infection with high morbidity and mortality. Order Mucorales belong to the class Mucormycetes, subsequently to the subphylum Mucoromycotina [1]. It is associated with immunocompromised patients. However, several immunocompromised with various conditions including those with uncontrolled diabetes mellitus (DM), diabetic ketoacidosis, open wound following trauma, prolonged neutropenia, HIV or AIDS infection, iron overload or hemochromatosis, malignancies, corticosteroid therapy, organ transplant, and severe burns predispose this infection [2]. Although Mucorales belongs to nonpathologic fungus, the prevalence in immunocompetent individuals is a result of the existence of an intact immunity through neutrophils, which eliminate their spores [2,3]. Recently, severe COVID-19 infection was added as a co-factor that might cause a significant and sustained lymphopenia, leading to developing opportunistic infections, either bacterial or fungal. The first case was reported with COVID-19, which developed pulmonary cavitary lesions due to Mucorales fungi co-infection with harmful complications [3]. In fact, Mucorales fungi can invade blood vessels, which causes ischemic necrosis, and can potentially invades various systems such as the lung, central nervous system (CNS), nose, sinuses, skin, orbit, jaw bones, joints, heart, and kidney and can be classified into the following forms: pulmonary, rhino-cerebral, sino-nasal, cutaneous, oral mycosis, gastrointestinal, and disseminated [4]. This review article aimed to update the MCM information involving fungus classification, epidemiology, etiology, diagnostic tools, clinical settings, and treatment recommendations for invasive mycosis, which were found via the available original articles, original case reports, or published case series. Thus, this effort benefits to analyze and understand MCM via the available literature.
1.1 What is MCM?
MCM, previously known as zygomycosis, is the third most common invasive fungal infection after candidiasis and aspergillosis [2]. It is caused by mucoralean fungi (order Mucorales) [5]. Regarding a systematic position, the Mucorales order is considered more famous than the other zygosporic fungi orders (Entomophthorales and Mortierellales) [6]. Order Mucorales belonging to class Phycomycetes consequently to subphylum Mucoromycotina, thus phylum Mucoromycotina (Zygomycota) [7]. Mucorales containing the family Mucoraceae, which are classified into genus (species) Lichterman (formerly Absidia) (L. corymbifera), Apophysomyces (A. elegans), Mucor (circinelloides, hiemalis, racemosus, ramosissimus, rouxianus), Rhizomucor (R. pusillus, mishear), Rhizopus (R. arrhizus, microsporus, schipperae, stolonifer) (Figure 1) [8,9]. However, the order Entomophthorales contains two genera, Conidiobolus and Basidiobolus, which have been linked to human infections known as entomophthoromycosis. Mucorales are known to play a critical role in the development of MCM. In the last decade, according to molecular phylogenetic studies, the taxonomy of Mucorales has been modified widely and classified into 55 genera involving 261 species [10,11]. Thirty-eight species only have occasionally been implicated in MCM. But most of MCM infection (about 70–80%) is attributed to Mucor rouxii, L. corymbifera, R. pussillus, and R. arrhizus (formerly R. oryzae) [1,12,13,14] (Table 1).
Classification of a common fungal species involved in the induction of mucormycosis.
Update synonyms of medically important Mucorales species regarding to recent taxonomy [21]
| Current nomenclature | Former names/synonyms |
|---|---|
| Lichtheimia ramosa | Absidia ramosa, Mycocladus ramosus |
| Lichtheimia corymbifera | Absidia corymbifera, Mycocladus corymbifer |
| Lichtheimia ornata | Absidia ornata |
| Mucor circinelloides | Rhizomucor regularior, Rhizomucor variabilis |
| Mucor ardhlaengiktus | Mucor ellipsoideus, Mucor circinelloides |
| Mucor griseocyanus | Mucor circinelloides |
| Mucor janssenii | Mucor circinelloides |
| Mucor irregularis | Rhizomucor variabilis |
| Mucor lusitanicus | Mucor circinelloides |
| Rhizopus microsporus | Rhizopus azygosporus, Rhizopus chinensis, Rhizopus oligosporus, Rhizopus rhizopodiformis, Rhizopus tuberosus |
| Rhizopus arrhizus | Rhizopus oryzae |
1.2 Major epidemiological and clinical manifestations of MCM infection in patients with COVID-19
Currently, 213 cases have been confirmed as COVID-19–associated mucormycosis (CAM) in many countries like India (129 cases, 59.7%), followed by Egypt (44 cases, 20.37%), Turkey (12 cases, 5.6%), the United States (9 cases, 4.16%), Iran (4 cases, 1.8%), the Netherlands (4 cases, 1.8%), France (3 cases, 1.3%), Brazil (1 case, 0.4%), the UK (2 cases, 0.9%), Italy (1 case, 0.4%), Mexico (1 case, 0.4%), Spain (2 cases, 0.9%), and Austria (1 case, 0.4%). The data are presented in Table 2 and summarized in Table 3. The most common isolated Mucorales included Rhizopus spp., Mucor spp., Lichtheimia, and Aspergillus spp. Of note, most of them have rhino-orbito-cerebral MCM (100 cases, 45.3%), followed by rhino-orbital MCM (68 cases, 30.5%). Pulmonary MCM was observed in 24 cases (10.8%). However, sino-orbital was observed in 14 patients (6.3%), and gastrointestinal MCM was observed in 8 patients (4.0%). In addition, palatal ulcer MCM was observed in one case, abdominal MCM in two cases, musculoskeletal MCM in one case, maxillofacial MCM in two cases, and cutaneous MCM in one case. Regarding risk factors, the majority of patients with CAM have diabetes mellitus (93 cases, 42.7%), diabetes ketoacidosis (18 cases, 8%), hypertension (46 cases, 20.4%), or other comorbidities (8 cases, 3.6%). Patients who have received glucocorticoids were 67 cases (31.0%). A majority of patients were treated with amphotericin B as a primary antifungal agent with surgical debridement. Of these, 57 cases (27.3%) were deceased, 13 cases (6.0%) lost to follow-up, and 143 cases (66.6%) were alive. Data related to MCM and COVID-19 in the KSA and most Middle East countries are still limited.
Summary of mucormycosis (MCM) co-infected with COVID-19
| Number of cases | Country | Clinical presentation of MCM | Site of infection | Species | Underlying host risk factor | Diagnostics | Antifungal therapy | Outcome | Reference |
|---|---|---|---|---|---|---|---|---|---|
| 1 | USA | Rhino-orbital | Nasal sinus, orbit | NA | DKA, HTN, asthma | CT scan, histopathological and microbiological | Liposomal Amphotericin B | Improved | [94] |
| 2 | USA | Rhino-orbital-cerebral | Nasal sinus, orbit, CNS | NA | DM, DKA, received corticosteroids | CT scan, histopathological, and microbiological | Not mentioned | Died (n = 1), unchanged (n = 1) | [93] |
| 1 | UK | Pulmonary | Lung | NA | HTN, obesity, hypothyroidism | Q PCR, histochemical and immunohistochemistry examination | Not mentioned | Autopsy report | [109] |
| 1 | USA | Pulmonary | Lung | Rhizopus species | Not mentioned | CT scan, cultural examination | Amphotericin B | Died | [95] |
| 11 | India | Rhino-orbital-cerebral | Nasal sinus, orbit CNS majority | NA | DM, HTN | Cultural and histopathological examination CT scan | Amphotericin B | Died (n = 2), LFU (n = 5), improved (n = 4) | [106] |
| 1 | USA | Rhino-orbital | Nasal sinus, orbit | NA | DM, DKA | Histopathological and microbiological examination | Echinocandins and amphotericin B | Improved | [97] |
| 10 | India | Rhino-orbital-cerebral | Nasal sinus, orbit 1 = CNS | Rhizopus spp. | DM, DKT, received corticosteroid | Radiological and microbiological examination | Liposomal amphotericin B, dexamethasone | Died (n = 4), improved (n = 2), survived (n = 4) | [104] |
| 1 | USA | Pulmonary | Lung | Rhizopus azygosporus | Non mentioned | CT scan, histopathological Microbiological examination | Echinocandins and amphotericin B | Died | [99] |
| 1 | USA | Cutaneous | Skin | Rhizopus microsporus | DM, heart transplantation, received corticosteroid | CT scan cultural and microbiological examination | Amphotericin B, Caspofungin | Died | [100] |
| 23 | India | Rhino-orbital-cerebral | All-nasal sinus 10 = orbit 2 = CNS | NA | DM HTN received corticosteroid | MRI, CT scan | Surgical debridement, amphotericin B | LFU (n = 2), survived (n = 21) | [108] |
| 1 | Italy | Pulmonary | Nasal sinus lung | Rhizopus spp. | HTN | CT scan examination and histopathological examination | Amphotericin B | Died | [3] |
| 1 | France | Pulmonary | Lung | Rhizopus microsporus | Lymphoma, hematopoietic stem cell transplantation | Fungal qPCR CT scan | Liposomal amphotericin B | Died | [114] |
| 1 | India | Sino-orbital | Nasal sinus, orbit | Rhizopus oryzae | Received corticosteroid | MRI, histopathological examination | Surgery debridement, fluconazole, amphotericin B | Improved | [112] |
| 2 | Iran | Rhino-orbito-cerebral | 2 = nasal sinus 2 = orbit 1 = CNS | NA | 1 = DM, received corticosteroid | Histopathology CT scan | Endoscopic sinus debridement, amphotericin B | Died (n = 1), improved (n = 1) | [116] |
| 6 | India | Rhino-orbital-cerebral | All = nasal sinus, All = orbit 5 = CNS | NA | DM, received corticosteroid | Cultural, and histopathological examination, MRI | liposomal amphotericin B, posaconazole, surgical debridement | Improved | [103] |
| 1 | Mexico | Rhino-orbital | Nasal sinus, orbit | NA | DKA | Cultural examination, CT scan | Surgery debridement | Died | [118] |
| 1 | Austria | Pulmonary | Lung | Rhizopus microsporus | Leukemia | CT scan examination and histopathological examination | Voriconazole | Died | [119] |
| 1 | India | Rhino-orbital | Nasal sinus, orbit | NA | Not mentioned | MRI CT scan | Vancomycin, amphotericin B | Died | [110] |
| 1 | India | Pulmonary | Lung | Rhizopus microsporus | DM, HTN | CT scan, microbiological examination | Amphotericin B | Improved | [109] |
| 1 | Iran | Rhino-orbital | Nasal sinus, orbit | NA | NOD, received corticosteroid | Histopathological examination, CT scan | Unknown | Improved | [115] |
| 1 | India | Rhino-sinuses | Nasal sinus, orbit | NA | DM, | MRI, histopathological examination | Endoscopic sinus surgery, amphotericin B | Improved | [113] |
| 1 | India | Rhino-orbital–cerebral | Nasal sinus, orbit, CNS | NA | DM, NDD | CT scan, MRI, histopathological examination | Amphotericin B | Improved | [102] |
| 1 | USA | Pulmonary | Lung | Rhizopus arrhizus | DM, received corticosteroid | CT scan, histopathological, and microbiological examination | Not mentioned | Improved | [98] |
| 10 | India | Rhino-orbital | All = nasal sinus 2 = orbit 1- bone | NA | DM | Histopathological examination, CT scan, and MRI | Amphotericin B | Died (n = 1), survived (n = 3), improved (n = 5), LFU (n = 1) | [105] |
| 11 | India | Rhino-orbital-cerebral | Nasal sinus, orbit, CNS majority | NA | DM, HTN | Cultural and histopathological examination, CT scan | Amphotericin B | Died (n = 2), LFU (n = 5), improved (n = 4) | [106] |
| 1 | USA | Rhino-orbital -cerebral | Nasal sinus, CNS | Rhizopus species | DM, asthma, HTN, hyperlipidemia | CT scan, histopathological and microbiological examination | Endoscopic surgical debridement, vancomycin, cefepime, liposomal amphotericin B | Died | [96] |
| 1 | Brazil | Gastrointestinal | Gastrointestinal | NA | HTN | Esophagogastroduod, CT scan, histopathological examination | Unknown | Died | [101] |
| 1 | Turkey | Rhino-orbito-cerebral | Nasal sinus, orbit CNS | NA | DKA. received corticosteroid | Cultural examination, CT scan | Surgery debridement, amphotericin B | Died | [117] |
| 1 | Brazil | Palatal ulcer | Ulcerated, lesion with, coagulative, necrosis, hemorrhage, and abundant neutrophils | NA | DM | Histopathological examination, cultural examination, CT scan | Surgery debridement, amphotericin B | Survived | [117] |
| 1 | India | Rhino‑orbital | Periorbital pain followed by sudden onset of vision loss in the left eye | NA | DM | Histopathologic identification, cultural examination, CT scan | Surgery debridement, amphotericin B | Survived | [118] |
| 31 | India | Rhino‑orbital | Orbital cellulitis, ophthalmoplegia | NA | DM received corticosteroid (n = 19) | Cultural examination, CT scan | Surgery debridement, amphotericin B | Survived (n = 28), died (n = 3) | [119] |
| 1 | Iran | Rhino-orbital | Variable | NA | DM received corticosteroid | Histopathological examination | Combined antifungal, surgery debridement | Died | [120] |
| 1 | India | Gastrointestinal | Abdominal pain, nausea, vomiting | NA | NA | Histopathological examination, cultural examination, CT scan | Liposomal amphotericin B | Improved | [121] |
| 10 | India | Rhino-orbital | Headache and facial pain | NA | Received corticosteroid | Histopathological examination, cultural examination, CT scan | Amphotericin B, deoxycholate, and isavuconazole | Died (n = 1), survived (n = 9) | [122] |
| 6 | India | Paranasal sinusitis | Headache and facial pain | NA | DM | Histopathological examination, cultural examination, CT scan | Surgery debridement, amphotericin B | Improved (n = 6) | [123] |
| 1 | India | Abdominal | Abdominal pain, nausea, vomiting | NA | DM | Radiographic and histopathology in selected patients | Surgery debridement, amphotericin B | Died | [124] |
| 1 | India | Rhino-orbital | Acute loss of vision | NA | NA | Histopathological examination | Surgery debridement, amphotericin B | Recovered | [125] |
| 2 | Spain | Abdominal (n = 1), musculoskeletal (n = 2) | Abdominal and facial pain, | NA | DM, kidney transplantation (n = 1), HTN, steroid taken (n = 2) | Culture from the necrotic tissue | Surgery debridement, amphotericin B (n = 2), and initially isavuconazole, and subsequently posaconazole (n = 1) | Died (n = 1), survived (n = 1) | [126] |
| 11 | Turkey | Rhino-orbital (n = 8). Rhino-orbito –cerebral (n = 3) | 8 = nasal sinus, 8 = orbit 3 = CNS | NA | DM (n = 8), HTN (n = 7), renal failure (n = 5) | Cultural examination, CT scan | Radical debridement, amphotericin B | Died (n = 7), survived (n = 4) | [127] |
| 2 | India | Maxillo-facial | Facial pain | NA | DM (n = 1), HTN (n = 2) | Maxillary biopsy, cultural examination, CT scan | Radical debridement, amphotericin B | Survived (n = 2) | [128] |
| 8 | Egypt | Pulmonary | Respiratory system, orbital cavities, ethmoidal and maxillary sinuses, nasal cavity, nasopharynx, carotid artery, hard palate, skin | Aspergillosis | DM (n = 6), chronic kidney disease (n = 2), hyperlipidemia (n = 2), HTN (n = 2), ischemic heart disease (n = 1), cerebral infarction (n = 1) | Radiographic and histopathology in selected patients | Amphotericin B, ambisome, itraconazole, surgical debridement, orbital enucleation, mechanical ventilation | Survived (n = 5), died (n = 3) | [129] |
| 4 | Netherlands | Pulmonary, rhino-orbital, rhino-sinuses | Respiratory failure. Acute-onset kidney failure, extensive sinusitis | Rhizopus microsporus, Lichtheimia ramosa, A. fumigatus, R. arrhizus | DM (n = 2), chronic lymphocytic lymphoma (n = 1), obesity (n = 1) | Radiographic and culture | Tocilizumab, dexamethasone, prednisone, amphotericin B, posaconazole, voriconazole, isavuconazole, surgical debridement, interferon-γ, mechanical ventilatio | Died (n = 3), survived (n = 1) | [130] |
| 1 | UK | Pulmonary, heart, hilar nodes, brain, pharynx, nasal mucosa, trachea | Acute anterior cerebral artery, pneumonitis | Aspergillosis | Hypothyroidism, steatohepatitis, thrombo-embolic disease | PCR, radiographic and culture | Mechanical ventilation, aspirin, LMW-heparin, hydroxychloroquine, azithromycin, meropenem, teicoplanin, argatroban, noradrenaline, vasopressin, gentamicin, tracheostomy, bronchoalveolar lavage | Died | [131] |
| 36 | Egypt | Rhino-orbital–cerebral (n = 29), sino-orbital (n = 7) | Facial painfacial numbness, ophthalmoplegia, and visual loss | Mucor and Aspergillus species | DM (n = 10), HTN (n = 6), leukemia (n = 1), pancreatic cancer (n = 1), CKD (n = 3), asthma (n = 3), cardiac (n = 1), hypothyroidism (n = 1), systemic lupus erythematosus (n = 2) | MRI, histopathological diagnosis | Amphotericin B, voriconazole, posaconazole, surgical debridement, mechanical ventilation | Died (n = 13), survived (n = 23) | [132] |
| 2 | France | Pulmonary | Aspergillus | Obesity (n = 2), kidney transplantation (n = 1), HTN (n = 1), dyslipidemia (n = 1) | MRI, histopathological diagnosis | One had no specific antifungal or COVID-19 treatments (died later). One received no specific COVID-19 therapies, but voriconazole, amphotericin B, caspofungin, and isavuconazole for fungal infections (alive) | Died (n = 1), survived (n = 1) | [133] |
Q PCR, quantitive polymerase chain reaction; CT scan, computed tomography; MRI, magnetic resonance imaging; DM, diabetes mellitus; HTN, hypertension; CNS, central nervous system; GIT, gastro-intestinal tract; DKA, diabetic ketoacidosis; NOD, new-onset; NA, not available; LFU, lost to follow-up; LAMA, left against medical advice.
Summary of mucormycosis infection in COVID-19 patients
| Items | 213 cases (%) |
|---|---|
| Countries | |
| India | 129 (59.7) |
| Egypt | 44 (20.37) |
| Turkey | 12 (5.6) |
| USA | 9 (4.16) |
| Iran | 4 (1.8) |
| Netherland | 4 (1.8) |
| France | 3 (1.3) |
| Brazil | 1 (0.4) |
| UK | 2 (0.9) |
| Italy | 1 (0.4) |
| Mexico | 1 (0.4) |
| Spain | 2 (0.9) |
| Austria | 1 (0.4) |
| Clinical manifestations | |
| Rhino-orbito-cerebral | 100 (45.3) |
| Rhino-orbital | 68 (30.5) |
| Pulmonary | 24 (10.8) |
| Sino-orbital | 14 (6.3) |
| Gastrointestinal | 8 (4.0) |
| Others | 7 (3.1) |
| Risk factors | |
| Diabetes miletus | 93 (42.7) |
| Diabetes ketoacidosis | 18 (8) |
| Hypertension | 96 (42.7) |
| Another comorbidity | 8 (3.6) |
| Glucocorticoid’s intake | 67 (31.0) |
| Amphotericin B | Major |
| Surgical debridement | Major |
| Outcomes | |
| Deceased | 57 (27.3) |
| Alive | 143 (66.6) |
| Lost follow-up | 13 (6.0) |
1.3 Etiology
When healthy individuals with immunocompetent inhale or ingest the fungal spores or lacerations of the mucosa via the nasal passage or oral cavity, they will not be implicated in immediate or potential harm as the phagocytic response will limit its prevalence. In contrast to the individual with immunocompromised and low polymorphonuclear leukocytes, the fungi become pathogenic when individuals invade by the fungal spores through lacerations of the mucosa in the oral or nasal cavity, may develop hyphae, and reach the paranasal sinuses. Subsequently, the disease can develop and diffuse to the cavernous sinus, the orbits, and the brain. It can also invade the arterial lamina and lead to tissue necrosis or thromboembolisms and infarctions of involved tissues. Then, the patient might suffer from orbital cellulitis, orbital apex syndrome, cerebritis or brain abscess, and a high mortality rate [15]. Mucorales and Entomophthorales orders are the most common etiological agents of MCM in humans. Several co-factors have been reported for a steady increase in MCM risk, such as:
Immunosuppression following solid organ, stem cells, and bone marrow transplants [16].
Severe neutropenia consequence of aggressive chemotherapy for hematological and solid malignancies since neutrophils are essential for phagocytosis of the fungus [17].
Uncontrolled DM and insufficient healthcare access can lead to an increase in MCM risk factors and hyperglycemia, which contributes to impaired neutrophil function and may cause MCM [20]. Therefore, DM is the most commonly known risk factor for MCM, especially during ketoacidosis. This is because ketones facilitate the fungi to utilize and produce ketoreductase, which facilitates its growth. In addition, hyperglycemia with ketoacidosis is also directly associated with the risk of MCM in different ways: (a) incidence of iron imprisonment because of hyperglycation of iron, which reduces the host protective system; (b) enabling tissue breakthrough by expressing the glucose-regulated protein 78 (GRP78) of cell receptor, which binds to Mucorales fungal species through the direct effect of hyperglycemia and indirectly by raising free iron levels; (c) deteriorating phagocytic functions and diminution the efficiency of chemotaxis; and (d) enhancing fungal existence via iron dissociation from breakthrough proteins [21]. GRP78 was involved within the cell receptor of endothelial vascular tissue [22].
1.4 Environmental factors and distribution of MCM
From an environmental perspective, these fungi are distributed in the soil, compost, animal feces, and decaying materials. In France, the analysis of collected soil samples from different geographical zones demonstrated that the most common species of Mucoralean fungi are Mucor circinelloides, Rhizopus arrhizus (synonym: Rhizopus oryzae), Lichtheimia corymbifera, Rhizopus microsporus, and Cunninghamella bertholletiae [8,9]. In comparison, a novel species have been discovered in Mexico (Apophysomyces mexicanus) [23]. Thus, the most common species of Mucorales found in the European countries are Rhizopus spp. (34%), Mucor spp. (19%), and Lichtheimia spp. (19%) [24], whereas in the United States, Rhizopus species were followed by Mucor species (19%), Rhizomucor species (7%), Cunninghamella species (9%), and Lichtheimia species (formerly Absidia species, 3%) [5]. Of note, MCM incidence among geographical regions is possibly due to the different natural habitats [24]. Conversely, the peak of MCM incidence has been investigated from September to November (autumn season) in some Middle East countries [8,25,26], while in European countries, most incidences are recorded in autumn and winter [27]. As well as in tropical and subtropical zones, the distribution of MCM was higher in autumn [28], suggesting that climate conditions may play a critical role in the prevalence of MCM and might have contributed to increasing airborne spore concentrations in autumn, whereas the fewer concentrations occur in summer. MCM incidence varies considerably from zone to zone regarding the susceptibility of co-factors. Several studies from Europe [24,29,30] reported that hematological malignancy was the most co-factor of infection, while in India [27,31,32], Iran [33], Mexico [31], Middle East, and North Africa [34], it was DM. Conversely, several studies have demonstrated that the underlying disease is associated with the site of infection [13,28,35]. However, hematological malignancies and neutropenia are correlated with pulmonary MCM, whereas DM is correlated with sinusitis and rhino-cerebral disease, while trauma usually leads to cutaneous MCM. DM and ketoacidosis DM is contributing to underlying disease in cases with MCM globally [13,35].
1.5 Diagnosis
Fast treatment of MCM disease is considered a big challenge. Therefore, the accuracy of diagnosis is very important for helping the treatment and reducing the high mortality (85%, concerned with late or incorrect diagnosis) [2]. Continuous development and discovering an accurate diagnosis are still essential because of the indirect clinical markers/symptoms for confirming MCM. Update of studies is required to understand the epidemiology and diagnosis of this disease among various regions worldwide. In spite of this, multiple studies reported the difficulty in establishing a rapid diagnosis [36]. The first step in the diagnosis begins with suspicion of the occurrence of MCM infection, especially the candidate diseases as co-factors. Hence, progress in diagnosis has affected the increasing reports on invasive MCM in susceptible patients like those with diabetic ketoacidosis secondary to uncontrolled DM, HMs, solid organ transplant, chronic respiratory diseases, and corticosteroid therapy [37]. Although, a conventional clinical path for diagnosis lacks specificity and sensitivity. It is still a basic requirement for the initial diagnosis of MCM when a high indicator of suspicion, via estimate of host factors and fast evaluation of clinical appearances. For example, the initial investigation of gastric MCM by endoscopic examination usually reveals an ulcer with necrosis, ultimately presenting an adherent, thick, green exudate [38]. Histopathology and culture are the fundamentals of diagnosis [13,39]. Prompt microscopy examination of clinical biopsy specimens is carried out, perfectly using optical brighteners such as Blankophor and Calcofluor [40,41,42]. White in clinical specimens gives a fast visualization of the characteristic fungal hyphae of MCM, in this case requiring a fluorescent microscope [2,43]. Also, in the case of diplopia in diabetic patients, pleuritic pain may be an indicator of this infection, and it is essential to obtain a specimen for traditional examination by histopathological and microbiological examinations or by advanced molecular techniques. The markers and symptoms that involve diplopia are cranial nerve palsy, proptosis, sinus pain, orbital apex syndrome, periorbital swelling, and ulcers of the palate [42]. In addition, radiologically, various (≥10) nodules and pleural emissions can reveal the association with pulmonary MCM [44]. Other pathways are computerized tomography (CT) scans with high-resolution and magnetic resonance imaging (MRI), which indicate the existence of MCM [2,13,45]. When studying the CT features of COVID-19–associated pulmonary mucormycosis situations, it was discovered that consolidation and cavitation were the most common computed tomography imaging findings (69%), probably because of delayed disease diagnosis [46]. According to another CT imaging study, almost all the patients (95.7%) displayed signs of pansinusitis. The infection spread beyond the paranasal sinuses was seen in 78.7% of cases, with orbital invasion 40.4% being the most prevalent [47]. On the contrary, MRI is useful for soft tissue imaging and determining the severity of disease [48].
Conversely, identifying different fungal species is important for the best epidemiological understanding of MCM and may be of significance for outbreak determinations. Mucorales fungi can be easily identified in culture. One study described the morphological features alone, and when distinguished by specialists in the fungal investigation, a high level of accuracy can be obtained. [49,50] However, identifying species is still difficult and may face failures in speciation, whereas immunohistochemistry using monoclonal antibodies against R. arrhizus can differentiate aspergillosis from MCM (100% high sensitivity and 100% high specificity for MCM) [51,52]. Recently, a molecular diagnosis is required either for the identification or detection of MCM [53]. It involves conventional polymerase chain reaction (PCR), [54,55,56], restriction fragment length polymorphism (RFLP) [56,57], and DNA sequencing [2,58]. Indeed, several PCR-based techniques have been developed, such as nested PCR, real-time PCR [59,60] (quantitative PCR (qPCR)), nested PCR combined with RFLP [61], PCR coupled with electrospray ionization mass spectrometry [62], and PCR/high-resolution melt analysis [63]. All assays mentioned earlier can be applied for either the identification or the detection of Mucorales. Most of the molecular assays are ribosomal targets (18S, 28S, and internal transcribed spacer) or other DNA targets (the high-affinity iron permease I gene FTRI or cytochrome b) [53,64,65,66,67]. Several studies have been performed by using either fresh tissue specimens or formalin-fixed paraffin-embedded [68,69,70], yet resulting in different performances. Recent tools directed at molecular assays from blood serum [68,71,72,73] have yielded promising clinical data with the advantage of early diagnosis in comparison with culture. Moreover, qPCR has been performed to identify circulating Mucor/Rhizopus, Lichtheimia, and Rhizomucor DNA in the serum [74]. However, some studies recommended that molecular diagnosis can be conducted in addition to conventional diagnosis tools [75].
1.6 COVID-19 and mucormycosis co-infections
Based on clinical manifestations, invasive MCM can be classified by the anatomic site affected into six main forms: pulmonary, rhino-orbital-cerebral, cutaneous, sinus, gastrointestinal, disseminated, and rare forms, such as endocarditis, osteomyelitis, peritonitis, and renal infection [76,77,78]. Any of Mucorales species can infect any of these sites. Fungal infection can invade these sites by the incorporation or implantation of the fungal spores through oral, nasal, and conjunctival mucosa (rhino-orbital-cerebral), by inhalation (pulmonary), or by the ingestion of contaminated food (gastrointestinal), as they rapidly colonize nutriments rich of glucose for its principal energy source [79]. Then the common ratio of invasive MCM was evaluated as follows: sinuses (39%), pulmonary (24%), and cutaneous (19%) [80]. Dissemination developed in 23% of this infection [81,82]. However, these values may be changeable depending on the incidence of another co-factor such as COVID-19. The first report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species such as candidiasis, invasive aspergillosis, and pneumocystis jiroveci [83]. However, this report did not include MCM as a co-infection with the COVID-19 pandemic. Subsequently, the case report presented a patient with MCM without any conventional risk factor. The infection was confirmed after being diagnosed with COVID-19 and has been treated with broad-spectrum antibiotics and corticosteroids (which are critical factors for invasive fungal infection) [78,84]. Despite co-infection among patients with COVID-19 has been shown only in severe cases [82,85,86], superinfections in viral pneumonia remain unclear. The first reason is due to challenges confused by the conventional diagnosis of Mucorales. The second is due to the fact that many centers minimized direct testing of at-risk respiratory samples during the current COVID-19 pandemic to diminish exposure to the virus [87,88,89,90]. Subsequently, several reports confirmed increasing cases of MCM in different countries, particularly in India, after COVID-19. Of their findings of an even larger case series of MCM cases in COVID-19, about 80% of cases had DM and more than 75% of cases received a course of corticosteroids. Therefore, these findings indicated that the common triangle associated with COVID-19 and MCM co-infection are DM, diabetic ketoacidosis (DKA), and corticosteroids (Table 2) [3,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133]. However, some finding in case of rhino-orbital MCM was associated with ketoacidosis DM and infection with severe acquired respiratory syndrome coronavirus 2 [134]. Song et al. have reported an algorithm for the early diagnosis and management of common invasive fungal infections such as MCM, aspergillosis, candidiasis, and cryptococcosis during the COVID-19 pandemic [135]. However, factors leading to increased incidence of opportunistic fungal infections during the COVID-19 pandemic may lead to immunosuppression due to high-dose corticosteroids in the management of the pandemic, thus leading to immunosuppression [136]. Corticosteroid intake during COVID-19 infection often leads to uncontrolled diabetes and precipitation of ketoacidosis. Thus, acidosis (low pH) is considered a favorite media for Mucor spores to grow. In addition, corticosteroid intake also reduces the phagocytic activity of white blood cell (WBC) and causes deterioration of bronchoalveolar macrophages migration, ingestion, and phagolysosome fusion, leading to exposure risk of diabetic people to MCM [89]. Consequently, a report described one case with SARS-CoV-2 infection who developed a cavitary pulmonary MCM [137]. Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might develop coronavirus disease (COVID-19), which can be associated with significant and sustained lymphopenia compromising the immune system, especially in the most severe cases [3,138,139,140,141]. Recent findings described that a significant decrease in lymphocyte count and an increase in neutrophil count together with an inflammatory storm occur more frequently in patients who developed severe COVID-19 and co-infections [141]. Pathogenic mechanisms in aggressive MCM involve reduced phagocytic activity, attainable quantities of ferritin attributed to the displacement of protons by transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases with hemato-lymphohistiocytosis syndrome are associated with the increasing risk factors of invasive fungal co-infections [90]. Clinically, cell counts exhibited that there was an increase in neutrophils and WBC count, but a decrease in lymphocytes progressively [3]. In addition, corticosteroid intake also reduces the phagocytic activity of WBC and causes deterioration of bronchoalveolar macrophages migration, ingestion, and phagolysosome fusion, leading to a diabetic people exposure risk to MCM. Conversely, the presence of free iron is an ideal co-factor for MCM. Hyperglycemia leads to glycosylation of transferrin and ferritin, and minimizing iron-binding leads to a raised ratio of free iron. Moreover, an increase in interleukin (IL)-6 among COVID-19 patients also causes an increase in free iron by elevating ferritin levels, and acidosis increases free iron by reducing the ability of transferrin to chelate iron [89]. In addition, COVID-19 infection drastically affects the immune system via hyperexpression of booth proinflammatory (IL-1, IL-2, IL-6, and tumor necrosis factor (TNF-α)) and anti-inflammatory (IL-4, IL-10, and IL-17) cytokines [4,139] and hypoexpression of interferon (IFN)-γ. With an increase in neutrophiles, impaired lymphocyte-mediated immunity (Th1 and Th2) occurs. Subsequently, COVID-19 infection reduces the cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections [141]. Critical cases, especially those admitted to intensive care units and those requiring longer hospital stays might be more prospective to evolve fungal co-infections [142]. Therefore, it is to be noted that severe Covid-19 susceptible to opportunistic fungal co-infections, especially MCM.
1.7 Molecular mechanism of mucormycosis in COVID‑19 patients
The invasion of fungi usually starts by inhalation of spores during respiration (sometimes from ears), ingesting contaminated food, or invading through injuries/abrasion in the epidermis. Endothelialitis is the one factor of SARS-CoV-2 that might reveal the risk of MCM co-infection in COVID-19 patients. [143,144] Damage to endothelium promotes angio-invasion and prevalence of MCM. In addition, low pH, hyperglycemia, hyper-ferritin, and hyper-ketone due to COVID enhance an appropriate environmental condition for GRP78 of endothelial cells and fungal ligand spore coating homolog (CotH) protein. Molecular explanation between fungal CotH protein and nasal GRP78 enhances adherence in the early stage of infection (Figure 2). Then, the CotH surface proteins might act as invasion enzymes to cause the infection [145]. In the sequent step of infection, patients with the high levels of CotH and GRP78 lead to trapping of fungi inside sinus cavities (Figure 2) [146,147]. Then, fungal cells elongate into tube-like hyphal strands and disseminate into the sinuses, lungs, skin, soft tissues, and bloodstream, causing tissue and epithelium penetration (Figure 2). The second current pathway, corticosteroid intake, is the mainstay therapy in severe COVID-19 patients [148]. However, corticosteroid intake reduces the phagocytic capacity of WBCs, displaying patients’ fungal infections. In addition, new-onset corticosteroid-induced DM or exacerbated chronic DM with or without DKA might promote the replication of MCM. The COVID-19 itself launches a chain of events that might render patients prone to MCM infection. Thus, there are expected mechanisms through which SARS-CoV-2 infection might lead to MCM susceptibility. Dramatic elimination in the total number of T-cells involving both CD4+ and CD8+ groups in severe cases of COVID-19 causes significant lymphopenia successive an immunocompromised state and then susceptibility to MCM [4]. During severe COVID-19 infection, inflammatory cytokines such as IL-6, IL-2R, IL-10, and TNF-alpha elevate and lead to a term called “cytokine storm,” resulting in lymphopenia [4]. Consequently, cytokine storm raises iron levels and reduces its export. As a result, iron accumulates inside the cells. Iron overload causes tissue damage and necrosis. In addition, free iron is ideal for growth and spreading MCM (Figure 2) [149,150]. Moreover, SARS-induced pneumonia results in atelectasis, which results in COVID-19-contributed silent hypoxia. Usually, the hypoxia-inducible factor 1 (HIF-1) stays inactive in normal conditions. During hypoxic conditions of COVID-19, the HIF-1α transcription factor subunit has a risky role in the expression of the COVID-19 receptor gene (ACE-2 gene), and hypoxia causes endothelium damage and upregulation of adaptive and innate immunocytes [151,152]. The overall effect of HIF-1 results in raised localized inflammation and tissue damage in COVID-19 patients. In addition, COVID-19 infection has also been demonstrated to impact ferritin metabolism. Therefore, several studies have reported hyperferritinemia syndrome post-COVID-19 infection. Thus, high free iron levels lead also to tissue damage via the production of reactive oxygen species (ROS) [150,153,154,155,156]. The overall potentials such as corticosteroid therapy, immunocompromised state, DM, DKA, hyperglycemia, hypoxia, cytokine storm, hyperferritinemia, neutropenia, metabolic dysfunction, and ROS make COVID-19–infected patient more susceptible to MCM. These main symptoms increased the body temperature, and altered osmolarity make an ideal environment for the growth and development of MCM (Figure 2).
Proposed scheme revealed different pathways of mucormycosis post-COVID-19 infection. During fungal spore inhalation, fungal cells spore coat protein Cot H3 recognizes the GRP78 on nasal epithelial cells to invade, colonize, and lyse host cells. The overall potential such as corticosteroid therapy, immunocomprised, DM, DKA, hyperglycemia, hypoxia, cytokine storm, hyperferritinemia, neutropenia, metabolic dysfunction, LD, and ROS make COVID-19 infected patients increased growth mucormycosis. Abbreviations: GRP78, glucose-regulated protein 78; DM, diabetes mellitus; DKA, diabetic ketoacidosis; LD, lactate dehydrogenase; ROS, reactive oxygen; IL, interleukin.
1.8 Antifungal treatments
Progress in management and treatment of MCM is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, complete elimination via surgical debridement of infected tissues, and administration of assistant therapies [57]. The therapy includes available antifungal medicines such as azithromycin, oseltamivir, ceftriaxone, amphotericin B (liposomal), cefepime, meropenem, linezolid, caspofungin, vancomycin, piperacillin, tazobactam, and oseltamivir. Intravenous amphotericin B (a lipid formulation) is the best and most common medicine for initial treatment, especially with COVID-19 co-infection. Despite surgical operations and available antifungal drugs, the prognosis for recovery from MCM is poor [95,106] (Table 2). Kieliszek and Lipinski [157] suggested that the sodium selenite, but not selenate, possibly oxidizes viral thiol groups in the virus protein disulfide isomerase, coating it incapable to penetrate the host cell membrane. In this way, the sodium selenite inhibits invasion of viruses into the healthy cells and diminishes their infectivity [157]. Thus, this simple chemical compound is potentially applied to the recently infected COVID-19 patients all over the globe.
2 Conclusion
The increase in MCM worldwide due to co-factors, especially diabetes with or without ketoacidosis, leads to outbreaks of corticosteroid intake during the incidence of COVID-19 (increases in blood glucose lead to opportunistic fungal infection). Outbreaks of COVID-19 are accompanied by immunocompromised through hyperexpression of both proinflammatory (IL-1, IL-2, IL-6, and TNF-α) and anti-inflammatory (IL-4, IL-10, and IL-17) cytokines, and vice versa with IFN-γ. With an increase in neutrophils, impaired lymphocyte-mediated immunity (Th1 and Th2) occurs. Subsequently, COVID-19 infection leads to a reduction in the cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Therefore, it is to be noted that severe COVID-19 susceptible to opportunistic fungal co-infections, especially MCM. Every effort should be made to progress in the management and treatment of MCM is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal medicines. Corticosteroids were used only in cases co-infected with COVID-19 to reduce the load of mortal MCM.
Acknowledgments
The researchers would like to thank the Deanship of Scientific Research, Qassim University, for funding the publication of this project.
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Funding information: Authors received funding from the Qassim University.
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Author contributions: A.A.A., A.A.A., A.S., R.A., W.A.A.: study design and literature search. T.A., S.A.A., S.A., A.S.M.A., F.A.A., S.K.A., A.K.A., H.T.A., K.S.A., R.A.A., S.A.A., A.M.A., S.A.A., T.A.A., M.S.A., A.M.M., S.A.A., A.A.A., R.A., N.F.: literature search and the data collection for the preparation of the tables and figures. A.A.A. and Z.R.: manuscript drafting. All authors have read and approved the final manuscript for publication.
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Conflict of interest: Authors state no conflict of interest.
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Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
References
[1] Hibbett DS, Binder M, Bischoff JF, Blackwell M, Cannon PF, Eriksson OE, et al. A higher-level phylogenetic classification of the Fungi. Mycol Res. 2007 May;111(Pt 5):509–47. 10.1016/j.mycres.2007.03.004. Epub 2007 Mar 13. PMID: 17572334.Search in Google Scholar PubMed
[2] Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012 Feb;54(Suppl 1):S23–34. 10.1093/cid/cir866. PMID: 22247442.Search in Google Scholar PubMed
[3] Pasero D, Sanna S, Liperi C, Piredda D, Branca GP, Casadio L, et al. A challenging complication following SARS-CoV-2 infection: a case of pulmonary mucormycosis. Infection. 2021 Oct;49(5):1055–60. 10.1007/s15010-020-01561-x. Epub 2020 Dec 17. PMID: 33331988; PMCID: PMC7745708.Search in Google Scholar PubMed PubMed Central
[4] Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620–9. 10.1172/JCI137244. PMID: 32217835; PMCID: PMC7190990.Search in Google Scholar PubMed PubMed Central
[5] Chakrabarti A, Singh R. Mucormycosis in India: unique features. Mycoses. 2014 Dec;57(Suppl 3):85–90. 10.1111/myc.12243. Epub 2014 Sep 3. PMID: 25187095.Search in Google Scholar PubMed
[6] Hoog GSde, Guarro J, Gene JFM. Atlas of Clinical Fungi. 3rd edn. Utrecht, Netherlands: Cen; 2009. https://www.clinicalfungi.org/ Last accessed March 29, 2022.Search in Google Scholar
[7] Whittaker RH. New concepts of kingdoms or organisms. Evolutionary relations are better represented by new classifications than by the traditional two kingdoms. Science. 1969 Jan 10;163(3863):150–60. 10.1126/science.163.3863.150. PMID: 5762760.Search in Google Scholar PubMed
[8] Richardson M. The ecology of the zygomycetes and its impact on environmental exposure. Clin Microbiol Infect. 2009 Oct;15(Suppl 5):2–9. 10.1111/j.1469-0691.2009.02972.x. PMID: 19754749.Search in Google Scholar PubMed
[9] Mousavi B, Costa JM, Arné P, Guillot J, Chermette R, Botterel F, et al. Occurrence and species distribution of pathogenic Mucorales in unselected soil samples from France. Med Mycol. 2018 Apr 1;56(3):315–21. 10.1093/mmy/myx051. PMID: 28992337.Search in Google Scholar PubMed
[10] Bloch KC, Myint T, Raymond-Guillen L, Hage CA, Davis TE, Wright PW, et al. Improvement in diagnosis of histoplasma meningitis by combined testing for histoplasma antigen and immunoglobulin g and immunoglobulin m anti-histoplasma antibody in cerebrospinal fluid. Clin Infect Dis. 2018 Jan 6;66(1):89–94. 10.1093/cid/cix706. PMID: 29020213; PMCID: PMC5850023.Search in Google Scholar PubMed PubMed Central
[11] Malo J, Holbrook E, Zangeneh T, Strawter C, Oren E, Robey I, et al. Enhanced antibody detection and diagnosis of coccidioidomycosis with the miravista IgG and IgM detection enzyme immunoassay. J Clin Microbiol. 2017 Mar;55(3):893–901. 10.1128/JCM.01880-16. Epub 2017 Jan 4. PMID: 28053216; PMCID: PMC5328457.Search in Google Scholar PubMed PubMed Central
[12] Walther G, Wagner L, Kurzai O. Updates on the taxonomy of mucorales with an emphasis on clinically important taxa. J Fungi (Basel). 2019 Nov 14;5(4):106. 10.3390/jof5040106. PMID: 31739583; PMCID: PMC6958464.Search in Google Scholar PubMed PubMed Central
[13] Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005 Sep 1;41(5):634–53. 10.1086/432579. Epub 2005 Jul 29. PMID: 16080086.Search in Google Scholar PubMed
[14] Neofytos D, Horn D, Anaissie E, Olyaei A, Fishman J, Pfaller M, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis. 2009 Feb 1;48(3):265–73. 10.1086/595846. Erratum in: Clin Infect Dis. 2009 Mar 1;48(5):690. PMID: 19115967.Search in Google Scholar PubMed
[15] El Zein S, El-Cheikh J, El Zakhem A, Ibrahim D, Bazarbachi A, Kanj SS. Mucormycosis in hospitalized patients at a tertiary care center in Lebanon: a case series. Infection. 2018 Dec;46(6):811–21. 10.1007/s15010-018-1195-4. Epub 2018 Aug 18. Erratum in: Infection 2018 Sep 14: Erratum in: Infection. 2019 Jan 7. PMID: 30121719.Search in Google Scholar PubMed
[16] Hedayati MT, Taghizadeh Armaki M, Yazdani Charati J, Hedayati N, Seyedmousavi S, Denning DW. Burden of fungal infections in Iran. J Infect Dev Ctries. 2018 Oct 31;12(10):910–8. 10.3855/jidc.10476. PMID: 32004161.Search in Google Scholar PubMed
[17] Zafar S, Prabhu A. Rhino-orbito-cerebral mucormycosis: recovery against the odds. Pract Neurol. 2017 Dec;17(6):485–8. 10.1136/practneurol-2017-001671. Epub 2017 Aug 26. PMID: 28844040.Search in Google Scholar PubMed
[18] Sakamoto H, Itonaga H, Sawayama Y, Taguchi J, Saijo T, Kuwatsuka S, et al. Primary oral mucormycosis due to rhizopus microsporus after allogeneic stem cell transplantation. Intern Med. 2018;57(17):2567–71. 10.2169/internalmedicine.0474-17. Epub 2018 Sep 1. PMID: 30175728; PMCID: PMC6172532.Search in Google Scholar PubMed PubMed Central
[19] Ghuman H, Voelz K. Innate and adaptive immunity to mucorales. J Fungi (Basel). 2017 Sep 5;3(3):48. 10.3390/jof3030048. PMID: 29371565; PMCID: PMC5715954.Search in Google Scholar PubMed PubMed Central
[20] Fung M, Schwartz BS, Doernberg SB, Langelier C, Lo M, Graff L, et al. Breakthrough invasive fungal infections on isavuconazole prophylaxis and treatment: What is happening in the real-world setting? Clin Infect Dis. 2018 Sep 14;67(7):1142–3. 10.1093/cid/ciy260. PMID: 29617983; PMCID: PMC6692592.Search in Google Scholar PubMed PubMed Central
[21] Rausch CR, DiPippo AJ, Bose P, Kontoyiannis DP. Breakthrough fungal infections in patients with leukemia receiving isavuconazole. Clin Infect Dis. 2018 Oct 30;67(10):1610–3. 10.1093/cid/ciy406. PMID: 29771293; PMCID: PMC6454429.Search in Google Scholar PubMed PubMed Central
[22] Kontoyiannis DP. Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis. 2007 Apr 15;44(8):1089–90. 10.1086/512817. Epub 2007 Mar 2. PMID: 17366455.Search in Google Scholar PubMed
[23] Bavikar P, Mehta V. Rhino-orbital-cerebral mucormycosis: A fatal complication of uncontrolled diabetes mellitus. Cureus. 2017 Nov 13;9(11):e1841. 10.7759/cureus.1841. PMID: 29348987; PMCID: PMC5768320.Search in Google Scholar PubMed PubMed Central
[24] Binder U, Maurer E, Lass-Flörl C. Mucormycosis-from the pathogens to the disease. Clin Microbiol Infect. 2014 Jun;20(Suppl 6):60–6. 10.1111/1469-0691.12566. Epub 2014 Feb 24. PMID: 24476149.Search in Google Scholar PubMed
[25] Mousavi B, Botterel F, Costa JM, Arné P, Guillot J, Dannaoui E. Occurrence and species diversity of human-pathogenic Mucorales in commercial food-stuffs purchased in Paris area. Med Mycol. 2019 Aug 1;57(6):739–44. 10.1093/mmy/myy121. PMID: 30428080.Search in Google Scholar PubMed
[26] Bonifaz A, Stchigel AM, Guarro J, Guevara E, Pintos L, Sanchis M, et al. Primary cutaneous mucormycosis produced by the new species Apophysomyces mexicanus. J Clin Microbiol. 2014 Dec;52(12):4428–31. 10.1128/JCM.02138-14. Epub 2014 Oct 8. PMID: 25297328; PMCID: PMC4313335.Search in Google Scholar PubMed PubMed Central
[27] Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, et al. European Confederation of Medical Mycology Working Group on Zygomycosis. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 2011 Dec;17(12):1859–67. 10.1111/j.1469-0691.2010.03456.x. Epub 2011 Jul 1. PMID: 21199154.Search in Google Scholar PubMed
[28] Al-Ajam MR, Bizri AR, Mokhbat J, Weedon J, Lutwick L. Mucormycosis in the Eastern Mediterranean: a seasonal disease. Epidemiol Infect. 2006 Apr;134(2):341–6. 10.1017/S0950268805004930. PMID: 16490139; PMCID: PMC2870385.Search in Google Scholar PubMed PubMed Central
[29] El-Herte RI, Baban TA, Kanj SS. Mucormycosis: a review on environmental fungal spores and seasonal variation of human disease. Adv Infect Dis. 2012;2:76–81. 10.4236/aid.2012.23012.Search in Google Scholar
[30] Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi (Basel). 2019 Mar 21;5(1):26. 10.3390/jof5010026. PMID: 30901907; PMCID: PMC6462913.Search in Google Scholar PubMed PubMed Central
[31] Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol. 2006 Jun;44(4):335–42. 10.1080/13693780500464930. PMID: 16772227.Search in Google Scholar PubMed
[32] Lanternier F, Dannaoui E, Morizot G, Elie C, Garcia-Hermoso D, Huerre M, et al. French Mycosis Study Group. A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin Infect Dis. 2012 Feb;54(Suppl 1):S35–43. 10.1093/cid/cir880. PMID: 22247443.Search in Google Scholar PubMed
[33] Pagano L, Valentini CG, Posteraro B, Girmenia C, Ossi C, Pan A, et al. Zygomycosis in Italy: a survey of FIMUA-ECMM (Federazione Italiana di Micopatologia Umana ed Animale and European Confederation of Medical Mycology). J Chemother. 2009 Jun;21(3):322–9. 10.1179/joc.2009.21.3.322. PMID: 19567354.Search in Google Scholar PubMed
[34] Patel A, Kaur H, Xess I, Michael JS, Savio J, Rudramurthy S, et al. A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clin Microbiol Infect. 2020 Jul;26(7):944.e9–15. 10.1016/j.cmi.2019.11.021. Epub 2019 Dec 4. PMID: 31811914.Search in Google Scholar PubMed
[35] Cornely OA, Arikan-Akdagli S, Dannaoui E, Groll AH, Lagrou K, Chakrabarti A, et al. European Society of Clinical Microbiology and Infectious Diseases Fungal Infection Study Group; European Confederation of Medical Mycology. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect. 2014 Apr;20(Suppl 3):5–26. 10.1111/1469-0691.12371. PMID: 24479848.Search in Google Scholar PubMed
[36] Chakrabarti A, Chatterjee SS, Das A, Panda N, Shivaprakash MR, Kaur A, et al. Invasive zygomycosis in India: experience in a tertiary care hospital. Postgrad Med J. 2009 Nov;85(1009):573–81. 10.1136/pgmj.2008.076463. PMID: 19892892.Search in Google Scholar PubMed
[37] Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Med Mycol. 2019 Jun 1;57(4):395–402. 10.1093/mmy/myy060. PMID: 30085158.Search in Google Scholar PubMed
[38] Vaezi A, Moazeni M, Rahimi MT, de Hoog S, Badali H. Mucormycosis in Iran: a systematic review. Mycoses. 2016 Jul;59(7):402–15. 10.1111/myc.12474. Epub 2016 Feb 15. PMID: 26906121.Search in Google Scholar PubMed
[39] Corzo-León DE, Chora-Hernández LD, Rodríguez-Zulueta AP, Walsh TJ. Diabetes mellitus as the major risk factor for mucormycosis in Mexico: Epidemiology, diagnosis, and outcomes of reported cases. Med Mycol. 2018 Jan 1;56(1):29–43. 10.1093/mmy/myx017. PMID: 28431008.Search in Google Scholar PubMed
[40] Stemler J, Hamed K, Salmanton-García J, Rezaei-Matehkolaei A, Gräfe SK, Sal E, et al. Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature. Mycoses. 2020 Oct;63(10):1060–8. 10.1111/myc.13123. Epub 2020 Aug 29. PMID: 32485012.Search in Google Scholar PubMed
[41] Skiada A, Petrikkos G. Cutaneous zygomycosis. Clin Microbiol Infect. 2009 Oct;15(Suppl 5):41–5. 10.1111/j.1469-0691.2009.02979.x. PMID: 19754756.Search in Google Scholar PubMed
[42] Koushiappi E, Porfyridis I, Karagiannis C, Adamide T, Georgiou A. Pulmonary Mucormycosis (Zygomycosis) presenting as an infective exacerbation of chronic obstructive pulmonary disease. Eur J Case Rep Intern Med. 2018 Dec 27;5(12):000995. 10.12890/2018_000995. PMID: 30756000; PMCID: PMC6346968.Search in Google Scholar PubMed PubMed Central
[43] Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin Microbiol Infect. 2019 Jan;25(1):26–34. 10.1016/j.cmi.2018.07.011. Epub 2018 Jul 21. PMID: 30036666.Search in Google Scholar PubMed
[44] Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diagnosis of mucormycosis: An update. J Fungi (Basel). 2020 Nov 2;6(4):265. 10.3390/jof6040265. PMID: 33147877; PMCID: PMC7711598.Search in Google Scholar PubMed PubMed Central
[45] Moura DTH, Proença IM, McCarty TR, Sagae VMT, Ribeiro IB, Oliveira GHP, et al. Gastrointestinal manifestations and associated health outcomes of COVID-19: A brazilian experience from the largest South American public hospital. Clin (Sao Paulo). 2020 Oct 26;75:e2271. 10.6061/clinics/2020/e2271. PMID: 33146362; PMCID: PMC7561063.Search in Google Scholar PubMed PubMed Central
[46] Garg M, Prabhakar N, Muthu V, Farookh S, Kaur H, Suri V, et al. Findings of COVID-19-associated pulmonary mucormycosis: a case series and literature review. Radiology. 2022 Jan;302(1):214–7. 10.1148/radiol.2021211583. Epub 2021 Aug 31 PMID: 34463553; PMCID: PMC8717687.Search in Google Scholar PubMed PubMed Central
[47] Selarka L, Sharma S, Saini D, Sharma S, Batra A, Waghmare VT, et al. Mucormycosis and COVID‐19: An epidemic within a pandemic in India. Mycoses. 2021 Oct;64(10):1253–60. 10.1111/myc.13353.Search in Google Scholar PubMed PubMed Central
[48] Kamrul-Hasan AB, Selim S. Mucormycosis, the deadly new worry to COVID-19 pandemic. Mymensingh Med J. 2021 Jul 1;30(3):874–80. PMID: 34226483.Search in Google Scholar
[49] Legouge C, Caillot D, Chrétien ML, Lafon I, Ferrant E, Audia S, et al. The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia? Clin Infect Dis. 2014 Mar;58(5):672–8. 10.1093/cid/cit929. Epub 2013 Dec 18. PMID: 24352351.Search in Google Scholar PubMed
[50] Frater JL, Hall GS, Procop GW. Histologic features of zygomycosis: emphasis on perineural invasion and fungal morphology. Arch Pathol Lab Med. 2001 Mar;125(3):375–8. 10.5858/2001-125-0375-HFOZ. PMID: 11231486.Search in Google Scholar PubMed
[51] Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect. 2009 Oct;15(Suppl 5):60–5. 10.1111/j.1469-0691.2009.02999.x. PMID: 19754760.Search in Google Scholar PubMed
[52] Lass-Flörl C, Resch G, Nachbaur D, Mayr A, Gastl G, Auberger J, et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis. 2007 Oct 1;45(7):e101–4. 10.1086/521245. Epub 2007 Aug 20. PMID: 17806041.Search in Google Scholar PubMed
[53] Suganya R, Malathi N, Karthikeyan V. Mucormycosis: a brief review. J Pure Appl Microbiol. 2019;13:161–5. 10.22207/JPAM.13.1.16.Search in Google Scholar
[54] Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden RT, Kontoyiannis DP. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin Infect Dis. 2012 Feb;54(Suppl 1):S55–60. 10.1093/cid/cir868. PMID: 22247446.Search in Google Scholar PubMed
[55] Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyiannis DP. Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer. Clin Infect Dis. 2005 Jul 1;41(1):60–6. 10.1086/430710. Epub 2005 May 24. PMID: 15937764.Search in Google Scholar PubMed
[56] Patel NR, Patel PA. A case report of mucormycosis with palatal ulcer: A rare clinical dilemma. J Coll Physicians Surg Pak. 2018 Sep;28(9):721–3. 10.29271/jcpsp.2018.09.721. PMID: 30158044.Search in Google Scholar PubMed
[57] Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, et al. European Conference on Infections in Leukemia. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013 Apr;98(4):492–504. 10.3324/haematol.2012.065110. Epub 2012 Sep 14. PMID: 22983580; PMCID: PMC3659979.Search in Google Scholar PubMed PubMed Central
[58] Alvarez E, Sutton DA, Cano J, Fothergill AW, Stchigel A, Rinaldi MG, et al. Spectrum of zygomycete species identified in clinically significant specimens in the United States. J Clin Microbiol. 2009 Jun;47(6):1650–6. 10.1128/JCM.00036-09. Epub 2009 Apr 22. PMID: 19386856; PMCID: PMC2691065.Search in Google Scholar PubMed PubMed Central
[59] Yang M, Lee JH, Kim YK, Ki CS, Huh HJ, Lee NY. Identification of mucorales from clinical specimens: a 4-year experience in a single institution. Ann Lab Med. 2016 Jan;36(1):60–3. 10.3343/alm.2016.36.1.60. PMID: 26522761; PMCID: PMC4697345.Search in Google Scholar PubMed PubMed Central
[60] Jung J, Park YS, Sung H, Song JS, Lee SO, Choi SH, et al. Using immunohistochemistry to assess the accuracy of histomorphologic diagnosis of aspergillosis and mucormycosis. Clin Infect Dis. 2015 Dec 1;61(11):1664–70. 10.1093/cid/civ660. Epub 2015 Aug 3. PMID: 26240202.Search in Google Scholar PubMed
[61] Son HJ, Song JS, Choi S, Jung J, Kim MJ, Chong YP, et al. A comparison of histomorphologic diagnosis with culture- and immunohistochemistry-based diagnosis of invasive aspergillosis and mucormycosis. Infect Dis (Lond). 2020 Apr;52(4):279–83. 10.1080/23744235.2020.1716063. Epub 2020 Jan 23. PMID: 31973617.Search in Google Scholar PubMed
[62] Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E, Petrikkos G. Challenges in the diagnosis and treatment of mucormycosis. Med Mycol. 2018 Apr 1;56(suppl_1):93–101. 10.1093/mmy/myx101. PMID: 29538730; PMCID: PMC6251532.Search in Google Scholar PubMed PubMed Central
[63] Hsiao CR, Huang L, Bouchara JP, Barton R, Li HC, Chang TC. Identification of medically important molds by an oligonucleotide array. J Clin Microbiol. 2005 Aug;43(8):3760–8. 10.1128/JCM.43.8.3760-3768.2005. PMID: 16081907; PMCID: PMC1233923.Search in Google Scholar PubMed PubMed Central
[64] Nagao K, Ota T, Tanikawa A, Takae Y, Mori T, Udagawa S, et al. Genetic identification and detection of human pathogenic Rhizopus species, a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene. J Dermatol Sci. 2005 Jul;39(1):23–31. 10.1016/j.jdermsci.2005.01.010. Epub 2005 Feb 25. PMID: 15978416.Search in Google Scholar PubMed
[65] Larché J, Machouart M, Burton K, Collomb J, Biava MF, Gérard A, et al. Diagnosis of cutaneous mucormycosis due to Rhizopus microsporus by an innovative PCR-restriction fragment-length polymorphism method. Clin Infect Dis. 2005 Nov 1;41(9):1362–5. 10.1086/497078. PMID: 16206119.Search in Google Scholar PubMed
[66] Machouart M, Larché J, Burton K, Collomb J, Maurer P, Cintrat A, et al. Genetic identification of the main opportunistic Mucorales by PCR-restriction fragment length polymorphism. J Clin Microbiol. 2006 Mar;44(3):805–10. 10.1128/JCM.44.3.805-810.2006. PMID: 16517858; PMCID: PMC1393117.Search in Google Scholar PubMed PubMed Central
[67] Nyilasi I, Papp T, Csernetics A, Krizsán K, Nagy E, Vágvölgyi C. High-affinity iron permease (FTR1) gene sequence-based molecular identification of clinically important Zygomycetes. Clin Microbiol Infect. 2008 Apr;14(4):393–7. 10.1111/j.1469-0691.2007.01932.x. Epub 2008 Jan 11. PMID: 18190575.Search in Google Scholar PubMed
[68] Springer J, Lackner M, Ensinger C, Risslegger B, Morton CO, Nachbaur D, et al. Clinical evaluation of a Mucorales-specific real-time PCR assay in tissue and serum samples. J Med Microbiol. 2016 Dec;65(12):1414–21. 10.1099/jmm.0.000375. Epub 2016 Oct 24. PMID: 27902424.Search in Google Scholar PubMed
[69] Wong G, Wong I, Chan K, Hsieh Y, Wong S. A rapid and low-cost pcr thermal cycler for low resource settings. PLoS One. 2015 Jul 6;10(7):e0131701. 10.1371/journal.pone.0131701. PMID: 26146999; PMCID: PMC4492969.Search in Google Scholar PubMed PubMed Central
[70] Gholinejad-Ghadi N, Shokohi T, Seifi Z, Aghili SR, Roilides E, Nikkhah M, et al. Identification of Mucorales in patients with proven invasive mucormycosis by polymerase chain reaction in tissue samples. Mycoses. 2018 Dec;61(12):909–15. 10.1111/myc.12837. Epub 2018 Aug 28. PMID: 30091261.Search in Google Scholar PubMed
[71] Zaman K, Rudramurthy SM, Das A, Panda N, Honnavar P, Kaur H, et al. Molecular diagnosis of rhino-orbito-cerebral mucormycosis from fresh tissue samples. J Med Microbiol. 2017 Aug;66(8):1124–9. 10.1099/jmm.0.000560. Epub 2017 Aug 9. PMID: 28792370.Search in Google Scholar PubMed
[72] Alanio A, Garcia-Hermoso D, Mercier-Delarue S, Lanternier F, Gits-Muselli M, Menotti J, et al. French Mycosis Study Group Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry. Clin Microbiol Infect. 2015 Jun;21(6):594.e1–5. 10.1016/j.cmi.2015.01.017. Epub 2015 Jan 28. PMID: 25726039.Search in Google Scholar PubMed
[73] Lengerova M, Racil Z, Hrncirova K, Kocmanova I, Volfova P, Ricna D, et al. Rapid detection and identification of mucormycetes in bronchoalveolar lavage samples from immunocompromised patients with pulmonary infiltrates by use of high-resolution melt analysis. J Clin Microbiol. 2014 Aug;52(8):2824–8. 10.1128/JCM.00637-14. Epub 2014 May 21. PMID: 24850354; PMCID: PMC4136189.Search in Google Scholar PubMed PubMed Central
[74] Dannaoui E. Molecular tools for identification of Zygomycetes and the diagnosis of zygomycosis. Clin Microbiol Infect. 2009 Oct;15(Suppl 5):66–70. 10.1111/j.1469-0691.2009.02983.x. PMID: 19754761.Search in Google Scholar PubMed
[75] Garcia-Hermoso D. Diagnostic microbiologique des mucormycoses [Laboratory diagnosis of mucormycosis]. Med Sci (Paris). 2013;29(Spec No 1):13–8. 10.1051/medsci/201329s104.Search in Google Scholar PubMed
[76] Dadwal SS, Kontoyiannis DP. Recent advances in the molecular diagnosis of mucormycosis. Expert Rev Mol Diagn. 2018 Oct;18(10):845–54. 10.1080/14737159.2018.1522250. Epub 2018 Sep 19. PMID: 30203997.Search in Google Scholar PubMed
[77] Baldin C, Soliman SSM, Jeon HH, Alkhazraji S, Gebremariam T, Gu Y, et al. PCR-Based approach targeting mucorales-specific gene family for diagnosis of mucormycosis. J Clin Microbiol. 2018 Sep 25;56(10):e00746-18. 10.1128/JCM.00746-18. PMID: 30068535; PMCID: PMC6156309.Search in Google Scholar PubMed PubMed Central
[78] Lackner M, Caramalho R, Lass-Flörl C. Laboratory diagnosis of mucormycosis: current status and future perspectives. Future Microbiol. 2014;9(5):683–95. 10.2217/fmb.14.23. PMID: 24957094.Search in Google Scholar PubMed
[79] Legrand M, Gits-Muselli M, Boutin L, Garcia-Hermoso D, Maurel V, Soussi S, et al. Detection of circulating mucorales DNA in critically Ill burn patients: Preliminary report of a screening strategy for early diagnosis and treatment. Clin Infect Dis. 2016 Nov 15;63(10):1312–7. 10.1093/cid/ciw563. Epub 2016 Aug 17 PMID: 27535951.Search in Google Scholar PubMed
[80] Millon L, Larosa F, Lepiller Q, Legrand F, Rocchi S, Daguindau E, et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis. 2013 May;56(10):e95–101. 10.1093/cid/cit094. Epub 2013 Feb 18. PMID: 23420816.Search in Google Scholar PubMed
[81] Scherer E, Iriart X, Bellanger AP, Dupont D, Guitard J, Gabriel F, et al. Quantitative PCR (qPCR) Detection of Mucorales DNA in Bronchoalveolar Lavage Fluid To Diagnose Pulmonary Mucormycosis. J Clin Microbiol. 2018 Jul 26;56(8):e00289-18. 10.1128/JCM.00289-18. PMID: 29875192; PMCID: PMC6062785.Search in Google Scholar PubMed PubMed Central
[82] Guinea J, Escribano P, Vena A, Muñoz P, Martínez-Jiménez MDC, Padilla B, et al. Correction: Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: Epidemiology and microbiological characterization of the isolates. PLoS One. 2020 Feb 12;15(2):e0229347. 10.1371/journal.pone.0229347. Erratum for: PLoS One. 2017 Jun 7;12(6):e0179136. PMID: 32049980; PMCID: PMC7015364.Search in Google Scholar PubMed PubMed Central
[83] Ino K, Nakase K, Nakamura A, Nakamori Y, Sugawara Y, Miyazaki K, et al. Management of pulmonary mucormycosis based on a polymerase chain reaction (PCR) diagnosis in patients with hematologic malignancies: a report of four cases. Intern Med. 2017;56(6):707–11. 10.2169/internalmedicine.56.7647. Epub 2017 Mar 17. PMID: 28321075; PMCID: PMC5410485.Search in Google Scholar PubMed PubMed Central
[84] Millon L, Herbrecht R, Grenouillet F, Morio F, Alanio A, Letscher-Bru V, et al. French Mycosis Study Group Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF). Clin Microbiol Infect. 2016 Sep;22(9):810.e1–8. 10.1016/j.cmi.2015.12.006. Epub 2015 Dec 17. PMID: 26706615.Search in Google Scholar PubMed
[85] Kasai M, Harrington SM, Francesconi A, Petraitis V, Petraitiene R, Beveridge MG, et al. Detection of a molecular biomarker for zygomycetes by quantitative PCR assays of plasma, bronchoalveolar lavage, and lung tissue in a rabbit model of experimental pulmonary zygomycosis. J Clin Microbiol. 2008 Nov;46(11):3690–702. 10.1128/JCM.00917-08. Epub 2008 Sep 24. PMID: 18845827; PMCID: PMC2576616.Search in Google Scholar PubMed PubMed Central
[86] Goodman NL, Rinaldi MG. Agents of mucormycosis. In: Balows A, Hausler WJ, Herrmann KL, Isenberg HD, Shadoomy HJ, editors. Manual of clinical microbiology. 5th edn. Washington, DC: ASM Press; 1991. https://www.jstor.org/stable/41353455.Search in Google Scholar
[87] Lopes JO, Pereira DV, Streher LA, Fenalte AA, Alves SH, Benevenga JP. Cutaneous zygomycosis caused by Absidia corymbifera in a leukemic patient. Mycopathologia. 1995 May;130(2):89–92. 10.1007/BF01103455. PMID: 7566062.Search in Google Scholar PubMed
[88] Stas KJ, Louwagie PG, Van Damme BJ, Coosemans W, Waer M, Vanrenterghem YF. Isolated zygomycosis in a bought living unrelated kidney transplant. Transpl Int. 1996;9(6):600–2. 10.1007/BF00335563. PMID: 8914243.Search in Google Scholar PubMed
[89] Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 2021 Jul-Aug;15(4):102146. 10.1016/j.dsx.2021.05.019. Epub 2021 May 21. PMID: 34192610; PMCID: PMC8137376.Search in Google Scholar PubMed PubMed Central
[90] Dallalzadeh LO, Ozzello DJ, Liu CY, Kikkawa DO, Korn BS. Secondary infection with rhino-orbital cerebral mucormycosis associated with COVID-19. Orbit. 2021 Mar 23;1–4. 10.1080/01676830.2021.1903044. Epub ahead of print. PMID: 33752571.Search in Google Scholar PubMed
[91] Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med. 2021 Apr;42:264.e5–8. 10.1016/j.ajem.2020.09.032. Epub 2020 Sep 16. PMID: 32972795; PMCID: PMC7493738.Search in Google Scholar PubMed PubMed Central
[92] Placik DA, Taylor WL, Wnuk NM. Bronchopleural fistula development in the setting of novel therapies for acute respiratory distress syndrome in SARS-CoV-2 pneumonia. Radiol Case Rep. 2020 Nov;15(11):2378–81. 10.1016/j.radcr.2020.09.026. Epub 2020 Sep 18. PMID: 32983308; PMCID: PMC7500914.Search in Google Scholar PubMed PubMed Central
[93] Mekonnen ZK, Ashraf DC, Jankowski T, Grob SR, Vagefi MR, Kersten RC, et al. Acute invasive rhino-orbital mucormycosis in a patient with covid-19-associated acute respiratory distress syndrome. Ophthalmic Plast Reconstr Surg. 2021 Mar-Apr 01;37(2):e40–80. 10.1097/IOP.0000000000001889. PMID: 33229953; PMCID: PMC7927902.Search in Google Scholar PubMed PubMed Central
[94] Alekseyev K, Didenko L, Chaudhry B. Rhinocerebral mucormycosis and COVID-19 pneumonia. J Med Cases. 2021 Mar;12(3):85–9. 10.14740/jmc3637. Epub 2021 Jan 19. PMID: 33984095; PMCID: PMC8040444.Search in Google Scholar PubMed PubMed Central
[95] Johnson AK, Ghazarian Z, Cendrowski KD, Persichino JG. Pulmonary aspergillosis and mucormycosis in a patient with COVID-19. Med Mycol Case Rep. 2021 Jun;32:64–7. 10.1016/j.mmcr.2021.03.006. Epub 2021 Apr 7. PMID: 33842203; PMCID: PMC8025540.Search in Google Scholar PubMed PubMed Central
[96] Kanwar A, Jordan A, Olewiler S, Wehberg K, Cortes M, Jackson BR. A fatal case of Rhizopus azygosporus pneumonia following COVID-19. J Fungi (Basel). 2021 Feb 28;7(3):174. 10.3390/jof7030174. PMID: 33670842; PMCID: PMC7997212.Search in Google Scholar PubMed PubMed Central
[97] Khatri A, Chang KM, Berlinrut I, Wallach F. Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient – Case report and review of literature. J Mycol Med. 2021 Jun;31(2):101125. 10.1016/j.mycmed.2021.101125. Epub 2021 Apr 2. PMID: 33857916; PMCID: PMC8017948.Search in Google Scholar PubMed PubMed Central
[98] Monte Junior ESD, Santos MELD, Ribeiro IB, Luz GO, Baba ER, Hirsch BS, et al. Rare and fatal gastrointestinal mucormycosis (Zygomycosis) in a COVID-19 patient: a case report. Clin Endosc. 2020 Nov;53(6):746–9. 10.5946/ce.2020.180. Epub 2020 Nov 19. PMID: 33207116; PMCID: PMC7719411.Search in Google Scholar PubMed PubMed Central
[99] Revannavar SM, Supriya PS, Samaga L, Vineeth V. COVID-19 triggering mucormycosis in a susceptible patient: a new phenomenon in the developing world? BMJ Case Rep. 2021 Apr 27;14(4):e241663. 10.1136/bcr-2021-241663. PMID: 33906877; PMCID: PMC8088249.Search in Google Scholar PubMed PubMed Central
[100] Sen M, Lahane S, Lahane TP, Parekh R, Honavar SG. Mucor in a Viral Land: A Tale of Two Pathogens. Indian J Ophthalmol. 2021 Feb;69(2):244–52. 10.4103/ijo.IJO_3774_20. PMID: 33463566; PMCID: PMC7933891.Search in Google Scholar PubMed PubMed Central
[101] Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19 and orbital mucormycosis. Indian J Ophthalmol. 2021 Apr;69(4):1002–4. 10.4103/ijo.IJO_3763_20. Erratum in: Indian J Ophthalmol. 2021 Jul;69(7):1978. PMID: 33727 483; PMCID: PMC8012924.Search in Google Scholar PubMed PubMed Central
[102] Mishra N, Mutya VSS, Thomas A, Rai G, Reddy B, Mohanan AA, et al. A case series of invasive mucormycosis in patients with COVID-19 infection. Int J Otorhinolaryngol Head Neck Surg. 2021;7(5):867–70. 10.18203/issn.2454-5929.ijohns20211583.Search in Google Scholar
[103] Satish D, Joy D, Ross A. Balasubramanya: Mucormycosis co-infection associated with global COVID-19: a case series from India. Int J Otorhinolaryngol Head Neck Surg. 2021;7(5):815–20. 10.18203/issn.2454-5929.ijohns20211574.Search in Google Scholar
[104] Moorthy A, Gaikwad R, Krishna S, Hegde R, Tripathi KK, Kale PG, et al. SARS-CoV-2, uncontrolled diabetes and corticosteroids-an unholy trinity in invasive fungal infections of the maxillofacial region? a retrospective, multi-centric analysis. J Maxillofac Oral Surg. 2021 Sep;20(3):418–25. 10.1007/s12663-021-01532-1. Epub 2021 Mar 6. PMID: 33716414; PMCID: PMC7936599.Search in Google Scholar
[105] Sharma S, Grover M, Bhargava S, Samdani S, Kataria T. Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum. J Laryngol Otol. 2021 May;135(5):442–7. 10.1017/S0022215121000992. Epub 2021 Apr 8. PMID: 33827722; PMCID: PMC8060545.Search in Google Scholar
[106] Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe. 2020 Oct;1(6):e245–53. 10.1016/S2666-5247(20)30115-4. Epub 2020 Aug 20. PMID: 32844161; PMCID: PMC7440861.Search in Google Scholar
[107] Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus. 2020 Sep 30;12(9):e10726. 10.7759/cureus.10726. PMID: 33145132; PMCID: PMC7599039.Search in Google Scholar PubMed PubMed Central
[108] Garg D, Muthu V, Sehgal IS, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus disease (Covid-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia. 2021 May;186(2):289–98. 10.1007/s11046-021-00528-2. Epub 2021 Feb 5. PMID: 33544266; PMCID: PMC7862973.Search in Google Scholar PubMed PubMed Central
[109] Maini A, Tomar G, Khanna D, Kini Y, Mehta H, Bhagyasree V. Sino-orbital mucormycosis in a COVID-19 patient: A case report. Int J Surg Case Rep. 2021 May;82:105957. 10.1016/j.ijscr.2021.105957. Epub 2021 May 4. PMID: 33964720; PMCID: PMC8093005.Search in Google Scholar PubMed PubMed Central
[110] Saldanha M, Reddy R, Vincent MJ. Title of the Article: Paranasal Mucormycosis in COVID-19 Patient. Indian J Otolaryngol Head Neck Surg. 2021 Apr;22:1–4. 10.1007/s12070-021-02574-0. Epub ahead of print. PMID: 33903850; PMCID: PMC8060684.Search in Google Scholar PubMed PubMed Central
[111] Bellanger AP, Navellou JC, Lepiller Q, Brion A, Brunel AS, Millon L, et al. Mixed mold infection with Aspergillus fumigatus and Rhizopus microsporus in a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) patient. Infect Dis Now. 2021 Oct;51(7):633–5. 10.1016/j.idnow.2021.01.010. Epub 2021 Jan 27. PMID: 33527098; PMCID: PMC7839422.Search in Google Scholar PubMed PubMed Central
[112] Karimi-Galougahi M, Arastou S, Haseli S. Fulminant mucormycosis complicating coronavirus disease 2019 (COVID-19). Int Forum Allergy Rhinol. 2021 Jun;11(6):1029–30. 10.1002/alr.22785. Epub 2021 Mar 13. PMID: 33713565; PMCID: PMC8250489.Search in Google Scholar PubMed PubMed Central
[113] Veisi A, Bagheri A, Eshaghi M, Rikhtehgar MH, Rezaei Kanavi M, Farjad R. Rhino-orbital mucormycosis during steroid therapy in COVID-19 patients: A case report. Eur J Ophthalmol. 2021 Apr 10;11206721211009450. 10.1177/11206721211009450. Epub ahead of print. PMID: 33843287.Search in Google Scholar PubMed PubMed Central
[114] Sargin F, Akbulut M, Karaduman S, Sungurtekin H. Severe rhinocerebral mucormycosis case developed After COVID 19. J Bacteriol Parasitol. 2021;12:386–90.Search in Google Scholar
[115] Waizel-Haiat S, Guerrero-Paz JA, Sanchez-Hurtado L, Calleja-Alarcon S, Romero-Gutierrez L. A case of fatal rhino-orbital mucormycosis associated with new onset diabetic ketoacidosis and COVID-19. Cureus. 2021 Feb 5;13(2):e13163. 10.7759/cureus.13163. PMID: 33575155; PMCID: PMC7870113.Search in Google Scholar PubMed PubMed Central
[116] Zurl C, Hoenigl M, Schulz E, Hatzl S, Gorkiewicz G, Krause R, et al. Autopsy proven pulmonary mucormycosis due to Rhizopus microsporus in a critically ill COVID-19 patient with underlying hematological malignancy. J Fungi (Basel). 2021 Jan 27;7(2):88. 10.3390/jof7020088. PMID: 33513875; PMCID: PMC7912223.Search in Google Scholar PubMed PubMed Central
[117] Pauli MA, Pereira LM, Monteiro ML, de Camargo AR, Rabelo GD. Painful palatal lesion in a patient with COVID-19. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 Jun;131(6):620–5. 10.1016/j.oooo.2021.03.010.Search in Google Scholar PubMed PubMed Central
[118] Rao R, Shetty AP, Nagesh CP. Orbital infarction syndrome secondary to rhino-orbital mucormycosis in a case of COVID-19: Clinico-radiological features. Indian J Ophthalmol. 2021 Jun;69(6):1627–30. 10.4103/ijo.IJO_1053_21.Search in Google Scholar PubMed PubMed Central
[119] Ravani SA, Agrawal GA, Leuva PA, Modi PH, Amin KD. Rise of the phoenix: Mucormycosis in COVID-19 times. Indian J Ophthalmol. 2021 Jun;69(6):1563–8. 10.4103/ijo.IJO_310_21.Search in Google Scholar PubMed PubMed Central
[120] Pakdel F, Ahmadikia K, Salehi M, Tabari A, Jafari R, Mehrparvar G, et al. Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran. Mycoses. 2021 Oct;64(10):1238–52. 10.1111/myc.13334.Search in Google Scholar PubMed PubMed Central
[121] Singh RP, Gupta N, Kaur T, Gupta A. Rare case of gastrointestinal mucormycosis with colonic perforation in an immunocompetent patient with COVID-19. BMJ Case Rep. 2021 Jul 2;14(7):e244096. 10.1136/bcr-2021-244096.Search in Google Scholar PubMed PubMed Central
[122] Arjun R, Felix V, Niyas VKM, Kumar MAS, Krishnan RB, Mohan V, et al. COVID-19-associated rhino-orbital mucormycosis: a single-centre experience of 10 cases. QJM. 2022 Jan 5;114(11):831–4. 10.1093/qjmed/hcab176.Search in Google Scholar PubMed
[123] Saidha PK, Kapoor S, Das P, Gupta A, Kakkar V, Kumar A, et al. Mucormycosis of paranasal sinuses of odontogenic origin post COVID19 infection: a case series. Indian J Otolaryngol Head Neck Surg. 2021 Jun 17;1–5. 10.1007/s12070-021-02638-1.Search in Google Scholar PubMed PubMed Central
[124] Jain M, Tyagi R, Tyagi R, Jain G. Post-COVID-19 GASTROINTESTINAL INVASIVE MUCORMycosis. Indian J Surg. 2021 Jun 22;84:1–3. 10.1007/s12262-021-03007-6.Search in Google Scholar PubMed PubMed Central
[125] Arana C, Cuevas Ramírez RE, Xipell M, Casals J, Moreno A, Herrera S, et al. Mucormycosis associated with COVID-19 in two kidney transplant patients. Transpl Infect Dis. 2021 Aug;23(4):e13652. 10.1111/tid.13652.Search in Google Scholar PubMed PubMed Central
[126] Baskar HC, Chandran A, Reddy CS, Singh S. Rhino-orbital mucormycosis in a COVID-19 patient. BMJ Case Rep. 2021 Jun 24;14(6):e244232. 10.1136/bcr-2021-244232.Search in Google Scholar PubMed PubMed Central
[127] Bayram N, Ozsaygılı C, Sav H, Tekin Y, Gundogan M, Pangal E, et al. Susceptibility of severe COVID-19 patients to rhino-orbital mucormycosis fungal infection in different clinical manifestations. Jpn J Ophthalmol. 2021 Jul;65(4):515–25. 10.1007/s10384-021-00845-5.Search in Google Scholar PubMed PubMed Central
[128] Sai Krishna D, Raj H, Kurup P, Juneja M. Maxillofacial Infections in Covid-19 Era-Actuality or the Unforeseen: 2 Case Reports. Indian J Otolaryngol Head Neck Surg. 2021 May 17;1–4. 10.1007/s12070-021-02618-5.Search in Google Scholar PubMed PubMed Central
[129] Ashour MM, Abdelaziz TT, Ashour DM, Askoura A, Saleh MI, Mahmoud MS. Imaging spectrum of acute invasive fungal rhino-orbital-cerebral sinusitis in COVID-19 patients: A case series and a review of literature. J Neuroradiol. 2021 Sep;48(5):319–24. 10.1016/j.neurad.2021.05.007.Search in Google Scholar PubMed PubMed Central
[130] Buil JB, van Zanten ARH, Bentvelsen RG, Rijpstra TA, Goorhuis B, van der Voort S, et al. Case series of four secondary mucormycosis infections in COVID-19 patients, the Netherlands, December 2020 to May 2021. Euro Surveill. 2021 Jun;26(23):2100510. 10.2807/1560-7917.ES.2021.26.23.2100510.Search in Google Scholar PubMed PubMed Central
[131] Krishna V, Morjaria J, Jalandari R, Omar F, Kaul S. Autoptic identification of disseminated mucormycosis in a young male presenting with cerebrovascular event, multi-organ dysfunction and COVID-19 infection. IDCases. 2021;25:e01172. 10.1016/j.idcr.2021.e01172.Search in Google Scholar PubMed PubMed Central
[132] El-Kholy NA, El-Fattah AMA, Khafagy YW. Invasive fungal sinusitis in post COVID-19 patients: a new clinical entity. Laryngoscope. 2021 Dec;131(12):2652–8. 10.1002/lary.29632.Search in Google Scholar PubMed PubMed Central
[133] Fekkar A, Lampros A, Mayaux J, Poignon C, Demeret S, Constantin JM, et al. Occurrence of invasive pulmonary fungal infections in patients with severe COVID-19 ADMITTED to the ICU. Am J Respir Crit Care Med. 2021 Feb 1;203(3):307–17. 10.1164/rccm.202009-3400OC.Search in Google Scholar PubMed PubMed Central
[134] Xu W, Peng J, Li D, Tsui C, Long Z, Wang Q, et al. Transcriptional profile of the human skin pathogenic fungus Mucor irregulars in response to low oxygen. Med Mycol. 2018;56(5):631–44. 10.1093/mmy/myx081.Search in Google Scholar PubMed
[135] Torres-Narbona M, Guinea J, Martínez-Alarcón J, Muñoz P, Gadea I, Bouza E, et al. Impact of zygomycosis on microbiology workload: a survey study in Spain. J Clin Microbiol. 2007;45(6):2051–3. 10.1128/JCM.02473-06.Search in Google Scholar
[136] Lineberry KD, Boettcher AK, Blount AL, Burgess SD. Cutaneous mucormycosis of the upper extremity in an immunocompetent host: case report. J Hand Surg Am. 2012;37(4):787–91. 10.1016/j.jhsa.2011.11.010.Search in Google Scholar
[137] Flagothier C, Arrese JE, Quatresooz P, Pierard GE. Cutaneous mucormycosis. J Mycol Méd. 2006;16(2):77–81. 10.1016/j.mycmed.2006.02.003.Search in Google Scholar
[138] Song G, Liang G, Liu W. Fungal co-infections associated with global COVID-19 pandemic: a clinical and diagnostic perspective from China. Mycopathologia. 2020;185(4):599–606. 10.1007/s11046-020-00462-9.Search in Google Scholar
[139] Liu J, Li S, Liu J, Liang B, Wang X, Wang H, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020;55:102763. 10.1016/j.ebiom.2020.102763.Search in Google Scholar
[140] Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–33. 10.1056/NEJMoa2001017.Search in Google Scholar
[141] Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020;9(1):727–32. 10.1080/22221751.2020.1746199.Search in Google Scholar
[142] Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–81. 10.1016/S2213-2600(20)30079-5.Search in Google Scholar
[143] Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417–8. 10.1016/S0140-6736(20)30937-5.Search in Google Scholar
[144] Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120–8. 10.1056/NEJMoa2015432.Search in Google Scholar PubMed PubMed Central
[145] Morin-Sardin S, Nodet P, Coton E, Jany J-L. Mucor: a Janus-faced fungal genus with human health impact and industrial applications. Fungal Biol Rev. 2017;31:12–32. 10.1016/j.fbr.2016.11.002.Search in Google Scholar
[146] Morales-Franco B, Nava-Villalba M, Medina-Guerrero EO, Sánchez-Nuño YA, Davila-Villa P, Anaya-Ambriz EJ, et al. Host-pathogen molecular factors contribute to the pathogenesis of rhizopus spp. In diabetes mellitus. Curr Trop Med Rep. 2021 Jan 22;1–12. 10.1007/s40475-020-00222-1.Search in Google Scholar PubMed PubMed Central
[147] Alspaugh JA. Hostile takeover: fungal protein promotes host cell invasion. J Clin Invest. 2014 Jan;124(1):74–6. 10.1172/JCI73585.Search in Google Scholar PubMed PubMed Central
[148] Nehara HR, Puri I, Singhal V, Ih S, Bishnoi BR, Sirohi P. Rhinocerebral mucormycosis in COVID-19 patient with diabetes a deadly trio: Case series from the north-western part of India. Indian J Med Microbiol. 2021 Jul;39(3):380–3. 10.1016/j.ijmmb.2021.05.009.Search in Google Scholar PubMed PubMed Central
[149] Edeas M, Saleh J, Peyssonnaux C. Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? Int J Infect Dis. 2020 Aug;97:303–5. 10.1016/j.ijid.2020.05.110.Search in Google Scholar PubMed PubMed Central
[150] Perricone C, Bartoloni E, Bursi R, Cafaro G, Guidelli GM, Shoenfeld Y, et al. COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy. Immunol Res. 2020 Aug;68(4):213–24. 10.1007/s12026-020-09145-5.Search in Google Scholar PubMed PubMed Central
[151] Herrmann J, Mori V, Bates JHT, Suki B. Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia. Nat Commun. 2020 Sep 28;11(1):4883. 10.1038/s41467-020-18672-6.Search in Google Scholar PubMed PubMed Central
[152] Rahman A, Tabassum T, Araf Y, Al Nahid A, Ullah MA, Hosen MJ. Silent hypoxia in COVID-19: pathomechanism and possible management strategy. Mol Biol Rep. 2021 Apr;48(4):3863–9. 10.1007/s11033-021-06358-1.Search in Google Scholar PubMed PubMed Central
[153] Vargas-Vargas M, Cortés-Rojo C. Ferritin levels and COVID-19. Rev Panam Salud Publica. 2020 Jun 1;44:e72. 10.26633/RPSP.2020.72.Search in Google Scholar PubMed PubMed Central
[154] Shoenfeld Y. Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev. 2020 Jun;19(6):102538. 10.1016/j.autrev.2020.102538.Search in Google Scholar PubMed PubMed Central
[155] Gómez-Pastora J, Weigand M, Kim J, Wu X, Strayer J, Palmer AF, et al. Hyperferritinemia in critically ill COVID-19 patients - Is ferritin the product of inflammation or a pathogenic mediator? Clin Chim Acta. 2020 Oct;509:249–51. 10.1016/j.cca.2020.06.033.Search in Google Scholar PubMed PubMed Central
[156] Sonnweber T, Boehm A, Sahanic S, Pizzini A, Aichner M, Sonnweber B, et al. Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study. Respir Res. 2020 Oct 21;21(1):276. 10.1186/s12931-020-01546-2.Search in Google Scholar PubMed PubMed Central
[157] Kieliszek M, Lipinski B. Selenium supplementation in the prevention of coronavirus infections (COVID-19). Med Hypotheses. 2020 Oct;143:109878. 10.1016/j.mehy.2020.109878.Search in Google Scholar PubMed PubMed Central
© 2022 Abdullah S. Alkhamiss et al., published by De Gruyter
This work is licensed under the Creative Commons Attribution 4.0 International License.
Articles in the same Issue
- Biomedical Sciences
- Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
- The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
- Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
- LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
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- Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
- Regulation of miR-30b in cancer development, apoptosis, and drug resistance
- Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
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- Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
- Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
- Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
- Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
- Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
- Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
- Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
- Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
- Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
- Nutrition intervention in the management of novel coronavirus pneumonia patients
- circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
- Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
- Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
- Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
- Comparison of axon extension: PTFE versus PLA formed by a 3D printer
- Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
- A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
- Study on the mechanism of inhibiting patulin production by fengycin
- SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
- Relationship between blood clots and COVID-19 vaccines: A literature review
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- Bioinformatics network analyses of growth differentiation factor 11
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- Expression of Zeb1 in the differentiation of mouse embryonic stem cell
- Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
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- Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
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- Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
- MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
- Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
- BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
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- Animal Sciences
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- Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
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Articles in the same Issue
- Biomedical Sciences
- Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
- The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
- Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
- LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
- Association study of CLDN14 variations in patients with kidney stones
- Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
- Regulation of miR-30b in cancer development, apoptosis, and drug resistance
- Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
- Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
- Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
- Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
- Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
- Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
- Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
- Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
- Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
- Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
- Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
- Nutrition intervention in the management of novel coronavirus pneumonia patients
- circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
- Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
- Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
- Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
- Comparison of axon extension: PTFE versus PLA formed by a 3D printer
- Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
- A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
- Study on the mechanism of inhibiting patulin production by fengycin
- SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
- Relationship between blood clots and COVID-19 vaccines: A literature review
- Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
- Bioinformatics network analyses of growth differentiation factor 11
- NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
- Expression of Zeb1 in the differentiation of mouse embryonic stem cell
- Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
- Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
- Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
- Genetic susceptibility to high myopia in Han Chinese population
- Potential biomarkers and molecular mechanisms in preeclampsia progression
- Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
- Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
- The significance of PAK4 in signaling and clinicopathology: A review
- Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
- Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
- Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
- Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
- MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
- Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
- BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
- Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
- Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
- A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
- Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
- Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
- Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
- A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
- β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
- Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
- BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
- Mucormycosis co-infection in COVID-19 patients: An update
- Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
- Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
- Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
- Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
- Nasopharyngeal tuberculosis: A case report
- Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
- Aberrant pulmonary immune response of obese mice to periodontal infection
- Bacteriospermia – A formidable player in male subfertility
- In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
- Effects of KCa channels on biological behavior of trophoblasts
- Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
- Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
- Prognostic signature related to the immune environment of oral squamous cell carcinoma
- Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
- Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
- Role of MMP-2 and CD147 in kidney fibrosis
- Geometric basis of action potential of skeletal muscle cells and neurons
- Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
- Role of cerebellar cortex in associative learning and memory in guinea pigs
- Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
- Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
- Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
- Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
- Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
- Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
- Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
- Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
- One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
- S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
- Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
- Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
- Evaluation of prognostic markers in patients infected with SARS-CoV-2
- N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
- Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
- Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
- Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
- Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
- Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
- Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
- SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
- Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
- Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
- Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
- Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
- Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
- PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
- A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
- Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
- A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
- The role of erythrocytes and erythroid progenitor cells in tumors
- Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
- Abnormal methylation caused by folic acid deficiency in neural tube defects
- Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
- Plant Sciences
- Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
- Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
- Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
- Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
- Phytoremediation of pollutants from wastewater: A concise review
- Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
- Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
- Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
- Study on pecan seed germination influenced by seed endocarp
- Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
- The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
- Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
- Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
- Cloning and expression analysis of SERK1 gene in Diospyros lotus
- Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
- A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
- Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
- The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
- Food Science
- Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
- Binge eating disorder during COVID-19
- Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
- FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
- Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
- Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
- Functional constituents of plant-based foods boost immunity against acute and chronic disorders
- Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
- Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
- Ecology and Environmental Sciences
- Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
- Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
- Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
- Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
- Plant volatile organic compounds attractive to Lygus pratensis
- Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
- Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
- Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
- Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
- Bioengineering and Biotechnology
- Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
- Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
- Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
- Agriculture
- Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
- Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
- Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
- Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
- Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
- Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
- Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
- Animal Sciences
- Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
- Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
- SI: A Scientific Memoir
- Suggestions on leading an academic research laboratory group
- My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
- Erratum
- Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
- Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
- Retraction
- Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
