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COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping

Czech National Centre for Evidence-Based Healthcare and Knowledge Translation (Cochrane Czech Republic, Czech EBHC: JBI Centre of Excellence, Masaryk University GRADE Centre), Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
Independent Researcher, New Delhi 110062, India
Department of Public Health, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
Department of Nursing and Midwifery, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
Authors to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2021, 18(19), 10340;
Received: 29 July 2021 / Revised: 23 September 2021 / Accepted: 25 September 2021 / Published: 30 September 2021


Mucormycosis, a serious and rare fungal infection, has recently been reported in COVID-19 patients worldwide. This study aims to map all the emerging evidence on the COVID-19-associated mucormycosis (CAM) with a special focus on clinical presentation, treatment modalities, and patient outcomes. An extensive literature search was performed in MEDLINE (Ovid), Embase (Ovid), Cochrane COVID-19 Study Register, and WHO COVID-19 database till 9 June 2021. The primary outcome was to summarize the clinical presentation, treatment modalities, and patient outcomes of CAM. Data were summarized using descriptive statistics and presented in tabular form. This evidence mapping was based on a total of 167 CAM patients with a mean age of 51 ± 14.62 years, and 56.28% of them were male. Diabetes mellitus (73.65% (n = 123)), hypertension (22.75% (n = 38)), and renal failure (10.77% (n = 18)) were the most common co-morbidities among CAM patients. The most common symptoms observed in CAM patients were facial pain, ptosis, proptosis, visual acuity, and vision loss. Survival was higher in patients who underwent both medical and surgical management (64.96%). Overall mortality among CAM patients was found to be 38.32%. In conclusion, this study found a high incidence of CAM with a high mortality rate. Optimal glycemic control and early identification of mucormycosis should be the priority to reduce the morbidity and mortality related to CAM.

1. Introduction

The coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 228 million people globally, with about 4.7 million deaths as of 21 September 2021 [1]. The novel COVID-19 strains that have emerged this year are more severe variants of the disease and have resulted in higher intensive care unit (ICU) admissions, need for mechanical ventilation, and mortality [2,3]. This, consequently, has increased the burden on healthcare systems globally [4].
COVID-19 patients often have several comorbidities, including diabetes [5]. Ample evidence has found patients with comorbidities to be at higher risk of ICU admissions and mortality [5,6,7]. Study findings by Liu et al. from Wuhan Union Hospital found a more intense level of lymphocytopenia and cytokine storm in patients with severe COVID-19 compared to that in patients with mild disease [8]. Despite the colossal impact of this pandemic gripping the world, there are limited treatment options for it. COVID-19 patients in severe or critical stages (admitted to ICUs) are prescribed high doses of steroids as a life-saving measure [9]. Steroids suppress the immune system (decrease in CD4 + T and CD8 + T cells) to fight against the inflammation caused by the virus, thereby creating a favorable environment for other opportunistic infections [9,10]. This can make the immunocompromised COVID-19 patients more susceptible to a range of viral, bacterial, fungal, and other microbial co-infections [11]. Multiple studies have confirmed that patients with severe COVID-19 admitted to ICUs have a high occurrence of secondary infections and relatively infrequent bacterial co-infection [12,13,14].
Mucormycosis, a serious and rare fungal infection, has occurred concurrently in COVID-19 patients globally [15]. COVID-19-associated mucormycosis (CAM) notably created havoc in the second wave of COVID-19 in India. Mucormycosis, also known as black fungus, is an invasive fungal infection most commonly caused by species of the genus Rhizopus [16]. Other species causing this fungal infection include those belonging to the genera Apophysomyces, Absidia, Mucor, and others. Amongst the various types of mucormycosis, rhino-orbital-cerebral is the most common one [17]. Risk factors associated with the development of fungal infection among COVID-19 patients include diabetes, neutropenia, hematological malignancy, stem cell transplant recipients, patients receiving corticosteroid treatment, and individuals in the immunocompromised state [18,19]. Mucormycosis is associated with a high risk of all-cause mortality (54%), with mortality depending on body site infected, fungus type, and the patient’s overall condition [20].
This deadly fungal infection is clinically challenging and expensive to treat and puts a high toll on public health and a humanistic and economic burden on individuals and healthcare systems [21,22]. Low- and middle-income countries such as India witnessed a massive number of CAM cases in the second wave of COVID-19, leading to a collapse of the health system in the midst of the pandemic. The Indian government (state governments) declared mucormycosis as an outbreak in May 2021 [23]. Evidence from previous published studies was based on fewer cases and limited information [24,25].
Presently, more detailed evidence on the clinical presentation, treatment modalities, and patient outcomes is required. The preliminary search for mapping existing evidence was performed on 25 May 2021, in Epistemonikos, the international prospective register of systematic reviews (PROSPERO), Open Science Framework (OSF), Cochrane Library, and Jonna Briggs Institute (JBI) Evidence Synthesis, and no previous evidence mapping was identified. Therefore, we conducted this study with an objective to map all the emerging evidence on the CAM with a particular focus on each minute detail of clinical presentation, treatment modalities, and patient outcomes.

2. Materials and Methods

The proposed study was developed by adhering to the JBI methodology for evidence mapping and is reported as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Scoping Reviews (PRISMA-ScR) [26,27]. Compliance with the PRISMA-ScR is presented in Supplementary Table S1.
Furthermore, this review was conducted by adhering to our protocol registered prospectively at OSF with an identification number ( and published as a preprint at the Preprint Server for Health Sciences (medRxiv) [28]. There were slight deviations from the protocol; firstly, the critical appraisal was skipped as it is not mandatory as per the JBI guidelines. The second deviation was the inclusion of suspected COVID-19 cases with confirmed mucormycosis, as patients developed mucormycosis after recovery from COVID-19.

2.1. Eligibility Criteria

2.1.1. PCC Elements

According to the JBI reviewer’s manual, the following PCC (Population, Concept, and Context) elements were used for this review.
Participants: patients with confirmed COVID-19 (RT-PCR) and mucormycosis (either histologically or microbiologically confirmed) based on the definition of Centers for Disease Control and Prevention were included in the study. We also included studies with suspected COVID-19 patients (based on the included studies assessment) who had confirmed mucormycosis.
Concept and context: this review included all studies that described the clinical presentation, treatment modalities, and patient outcomes of CAM.

2.1.2. Types of Sources

We included analytical observational studies (cohort, case–control) and descriptive observational studies (case report, case series, cross-sectional).

2.1.3. Exclusion Criteria

Non-English language studies;
studies with no confirmed mucormycosis; and
systematic reviews, narrative reviews, editorials, opinions, and study protocols were excluded.

2.2. Information Sources and Search Strategy

A three-step search strategy was utilized to identify published, unpublished, or ongoing studies with no language restrictions. An initial limited search was undertaken in MEDLINE (Ovid), followed by analyzing the text words in the title and abstract and the index terms assigned to the articles. Slightly modified Ovid Expert Searches for COVID-19 were combined with keywords and index terms related to mucormycosis to perform the searches in MEDLINE (Ovid) [29] and Embase (Ovid) [30] (Appendix A).
On 9 June 2021, we conducted a second search in MEDLINE (Ovid), Embase (Ovid), Cochrane COVID-19 Study Register, and the World Health Organization (WHO) COVID-19 database.
Complete search strategies are presented in Supplementary Table S2 for each database with their respective hits. Third, the manual search of reference lists of all included studies and relevant systematic reviews was screened for any potentially eligible studies. Citation tracking was also performed for all the included articles.

2.3. Selection Process

Two independent reviewers (S.H. and H.B.) screened all the retrieved articles against the eligibility criteria. We included all those articles describing the mucormycosis case (diagnosed either based on histopathology, culture, or stain) in COVID-19-positive patients.
In the initial screening phase, articles were selected based on the title and abstract scanning. In the second phase, full-text screening was performed for the final inclusion of articles. Any confusion regarding study inclusion was resolved by discussion with the third reviewer (M.K.). A detailed description of the study selection process is shown using the PRISMA flow diagram in Figure 1.

2.4. Data Extraction

Two reviewers (S.H. and H.B.) independently extracted the data in a pre-designed data extraction template. The following information was extracted from all the eligible studies qualified for inclusion: study author, year of publication, country, study design, demographic characteristics of the population (age and sex), sample size, comorbidities, treatment for COVID-19, symptoms of mucormycosis, diagnosis of mucormycosis, identification of fungal species, treatment for mucormycosis, and patient outcomes. The included studies are described using descriptive statistics and presented in a tabular form.

3. Results

A total of 209 articles were identified by searching the selected sources. After removing duplicates, only 92 articles were found to be unique. After the full-text screening, 37 studies [31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67] qualified for inclusion in this evidence mapping study. Four additional articles [68,69,70,71] were identified by hand search during bibliography screening and citation tracking. Finally, a total of 41 articles were included in this review [31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71]. Refer to Supplementary Table S3 for the list of articles excluded during full-text screening with reason.

3.1. Studies Characteristics

Out of 41 studies, the majority of studies (n = 15) were from India with 82 mucormycosis cases, 9 studies with 9 cases of mucormycosis were from the USA, while only 3 studies were from Iran but with 17 mucormycosis cases. Most of the included studies were case reports (n = 27) followed by case series (n = 9), and the rest were of other study designs. Diabetes mellitus (73.65% (n = 123)), hypertension (22.75% (n = 38)), and renal failure (10.77% (n = 18)) were the most common co-morbidities among CAM patients. Diabetic ketoacidosis was observed in one-tenth of the diabetic patients.

3.2. Clinical Presentation

This evidence mapping was based on a total of 167 CAM patients with a mean age of 51 ± 14.62 years, of which 56.28% of them were male. COVID-19 was confirmed through the RT-PCR test in approximately three-fourth (74%) of the included studies.
The majority of the patients (76.04%) were treated using steroids, while only 11.64% of patients were treated with remdesivir to manage COVID-19. Most patients who developed mucormycosis had severe (based on included studies’ categorization) or critical COVID-19 (defined based on ICU status/mechanical ventilation).
Twenty-nine (17.57%) patients had concurrent CAM, while the remaining patients were diagnosed with CAM after an average of 19.24 days. Mucormycosis was diagnosed using stain (24 studies), culture (26 studies), or histopathology (30 studies), and nine studies diagnosed mucormycosis using all three diagnostic techniques. The Rhizopus species were the most common fungal species infecting CAM patients (13.77%).
Facial pain, ptosis, proptosis, visual acuity, and vision loss were the most common symptoms observed in CAM patients. Rhino-orbital (16%) followed by rhino-orbital-cerebral (11.3%) mucormycosis was the most common form of mucormycosis found in CAM patients (Table 1).

3.3. Treatment Modalities and Outcomes

Liposomal amphotericin B in various doses (5 mg/kg/day) was the most commonly used drug for managing mucormycosis infection in 158 patients (35 studies). Adjunct surgery was performed on 142 patients, and surgical debridement was the most common surgical procedure performed. Only 23 CAM patients were managed without surgery, and most of them (18 CAM patients) died between 7 to 62 days after the diagnosis of mucormycosis.
Survival was higher in patients who underwent both medical and surgical management (64.96%) than in CAM patients who underwent medical management only (21.73%). Overall mortality among CAM patients in the included studies was 38.32% (n = 64). The patients died between 6 to 90 days after mucormycosis diagnosis (Table 2).

4. Discussion

To the best of our knowledge, this is the most comprehensive and up-to-date evidence mapping aimed to explore the published and unpublished evidence on the clinical presentation, treatment modalities, and patient outcomes of CAM. The current body of evidence was based on the 41 studies that met our inclusion criteria and discussed the association of COVID-19 with mucormycosis.
Mucormycosis is a rare opportunistic infection, and COVID-19 patients are at risk of developing mucormycosis because of pre-compromised immune systems. A growing body of evidence supports that comorbidities (diabetes, transplantation, malignancies) and medications (steroids) make the patients more vulnerable to CAM [5,6,7]. A recent case report found an invasive pulmonary mucormycosis case in a patient after a short course of steroids [72]. Likewise, Pan et al. found mucormycosis in a patient with AIDS receiving short-term systemic steroids [73]. In our study, we found that COVID-19 patients with comorbidities had a higher occurrence of mucormycosis.
Around 50% of CAM cases in our study were reported from India. A possible reason for this could be the deadly COVID-19 delta variant wave infecting around half a million people every day in recent months and a high prevalence of diabetes mellitus in CAM patients [74]. Diabetes mellitus is a predisposing factor for the development of mucormycosis [75,76]. The potential mechanism behind this could be the aggravation of the inflammatory state due to hyperglycemia and activation of antiviral immunity [77]. The risk of developing CAM increases significantly in patients with diabetic ketoacidosis, where Mucorales use free iron levels in the serum for pathogenesis [78].
In our study, the number of male mucormycosis patients was twice the number of female patients. These findings are aligned with a previously published study by Roden et al. [79] that found mucormycosis in 65% of male patients.
Rhino-orbital and rhino-orbital-cerebral were the most common forms of mucormycosis observed in this study. In both forms of infection, the fungus invades the nasal mucosa and orbital wall and leads to the occurrence of symptoms such as facial pain, vision loss, proptosis, apoptosis, and ophthalmoplegia [80,81]. CAM patients who underwent both surgical and medical management had a better survival rate than those with medical management alone. Published studies from different parts of the world have also found better outcomes in mucormycosis patients who underwent combined surgical and medical management [82,83]. However, despite the best management of CAM patients, the overall mortality was high, suggesting the need for the early identification of cases.
Our study findings suggest that clinical practitioners (intensivists and their teams) should be alerted about the increased possibility of CAM in critically ill COVID-19 patients; therefore, they should act proactively and monitor for potential fungal and bacterial co-infections and secondary infections among the COVID-19 cohorts, especially the immunocompromised and diabetic patients [84]. Moreover, these findings call drug regulators and health systems, especially in low- and lower-middle-income countries, to implement strict policies for steroid stewardship.

4.1. Limitations

Like every study, this evidence mapping has few limitations. Firstly, we could not differentiate the outcome based on glycemic-controlled status due to the lack of information on the glycosylated hemoglobin value of the CAM patients with diabetes in the included studies. Secondly, there was variability in the definition of severity of COVID-19 in the included studies. Lastly, limited information (fungal species identified, RT-PCR result) in a few included studies was also a drawback.

4.2. Strengths

The major strength of this review was a large number of exhaustive literature searches in major databases, a protocol-oriented approach, most up-to-date evidence with sound methodology, and the capture of each minute detail of 167 CAM patients to make this review a one-stop source of information for CAM.

5. Conclusions

This evidence mapping found a high incidence of CAM with a high mortality rate. Therefore, clinicians should cautiously use the steroids using the risk–benefit analysis approach. Optimal glycemic control and early identification of mucormycosis should be the priority to reduce the morbidity and mortality related to CAM.

Supplementary Materials

The following are available online at, Table S1: PRISMA-ScR checklist, Table S2: Search strategy, Table S3: List of excluded articles.

Author Contributions

Conceptualization, S.H. and M.K.; methodology, S.H. and M.K.; formal analysis, S.H.; investigation, S.H. and H.B.; resources, M.K.; data curation, S.H. and H.B.; writing—original draft preparation, S.H.; writing—review and editing, S.H., H.B., A.R., J.K., A.P., S.S., R.L., A.K.N. and M.K.; supervision, S.H. and M.K.; funding acquisition, M.K. All authors have read and agreed to the published version of the manuscript.


S.H. was supported by the Operational Program Research, Development and Education Project, Postdoc2MUNI (Nno. CZ.02.2.69/0.0/0.0/18_053/0016952). A.R., J.K., A.P., R.L. and M.K. were supported by the INTER-EXCELLENCE grant number LTC20031 toward an International Network for Evidence-based Research in Clinical Health Research in the Czech Republic. The work of A.R. was also supported by Masaryk University grants MUNI/IGA/1543/2020 and MUNI/A/1608/2020.

Institutional Review Board Statement

The study was exempted from ethical approval due to its observational nature and the use of publicly accessible data.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author (S.H. or M.K.) upon reasonable request.


This work is dedicated to the more than 3 million worldwide fatalities and their families who have fallen victim to COVID-19.

Conflicts of Interest

The authors declare no conflict of interest.

Appendix A. MEDLINE® ALL <1946 to 8 June 2021> (Ovid)

#Search StringNo. of Results
1exp Coronavirus/77,269
2exp Coronavirus Infections/94,303
3(coronavirus* or corona virus* or OC43 or NL63 or 229E or HKU1 or HCoV* or ncov* or covid* or sars-cov* or sarscov* or Sars-coronavirus* or Severe Acute Respiratory Syndrome Coronavirus* or “Kawasaki like paediatric inflammatory multisystem syndrome” or “Kawasaki like pediatric inflammatory multisystem syndrome” or “PIMS-TS” or “Kawa-COVID-19” or “MIS-C” or “multisystem inflammatory syndrome in children” or pediatric multisystem inflammatory disease).mp.159,987
4(or/1–3) and ((20191* or 202*).dp. or 20190101:20301231.(ep).) (147001)147,001
54 not (SARS or SARS-CoV or MERS or MERS-CoV or Middle East respiratory syndrome or camel * or dromedary* or equine or coronary or coronal or covidence* or covidien or influenza virus or HIV or bovine or calves or TGEV or feline or porcine or BCoV or PED or PEDV or PDCoV or FIPV or FCoV or SADS-CoV or canine or CCov or zoonotic or avian influenza or H1N1 or H5N1 or H5N6 or IBV or murine corona*).mp.54,231
6((pneumonia or covid* or coronavirus* or corona virus* or ncov* or 2019-ncov or sars*).mp. or exp pneumonia/) and
7(2019-ncov or ncov19 or ncov-19 or 2019-novel CoV or sars-cov2 or sars-cov-2 or sarscov2 or sarscov-2 or SARS-2-nCoV or SARS-2-Cov or SARS-COV-19 or Sars-coronavirus2 or Sars-coronavirus-2 or SARS 2 coronavirus* or Severe Acute Respiratory Syndrome-CoV-2 or SARS-like coronavirus* or coronavirus-19 or covid19 or covid-19 or covid 2019 or ((novel or new or nouveau) adj2 (CoV or nCoV or covid or coronavirus* or corona virus or Pandemi*2)) or ((covid or covid19 or covid-19 or SARS-CoV-2) and pandemic*2) or (coronavirus* and pneumonia)).mp.144,923
8(COVID-19 or SARS-CoV-2).rx,px,ox,rn. or (COVID-19 or COVID-19 serotherapy or ORF7b protein, SARS-CoV-2 or ORF6 protein, SARS-CoV-2 or ORF8 protein, SARS-CoV-2 or pediatric multisystem inflammatory disease, COVID-19 related or envelope protein, SARS-CoV-2 or ORF7a protein, SARS-CoV-2 or spike protein, SARS-CoV-2 or ORF3a protein, SARS-CoV-2 or COVID-19 drug treatment or severe acute respiratory syndrome coronavirus 2 or membrane protein, SARS-CoV-2 or ORF1ab polyprotein, SARS-CoV-2 or nucleocapsid protein, Coronavirus or COVID-19 vaccine or COVID-19 diagnostic testing).os,ps,rn,rs.8460
9(“32185863” or “32172715” or “32227595” or “32140676” or “32246156” or “32267941” or “32176889” or “32169616” or “32265186” or “32253187” or “32152148” or “32053580” or “32179788” or “32213260” or “32205350” or “32188729” or “32152361” or “32277065” or “32088947” or “32240583” or “31917786” or “32127714” or “32047315” or “32020111” or “32240632” or “32243118” or “32267344” or “32239781” or “32396977” or “32402130” or “32243299” or “32807526” or “32344395” or “32403202” or “32389714” or “32416016” or “32405099” or “32976849” or “32685966” or “33221888” or “32379271” or “32188728” or “32221976” or “32417321” or “32489438” or “32332959” or “32943452” or “32807525” or “32826274” or “32898560” or “32293023” or “33159926” or “32919952” or “32835716” or “32619499” or “32663524” or “32392627” or “32392625” or “33037657” or “32777045” or “32521569” or “32492200” or “32930765” or “33075143” or “32237249” or “32683439” or “32495994” or “32344447” or “32896006” or “32240549” or “32438448” or “32425477” or “32951095” or “32274794” or “32750178” or “32463935” or “32428286” or “32491981” or “32930748” or “32119409” or “32432657” or “33003176” or “32459319” or “32822920” or “32878290” or “32270498” or “32250493” or “32512243” or “32837399” or “32426074” or “32199942” or “32839969” or “32639522” or “33073717” or “32502134” or “32334003” or “32510470” or “32819741” or “32309248” or “32243951” or “32378772” or “32835361” or “32962779” or “32916324” or “32785973” or “32272221” or “32299207” or “33044515” or “33134955” or “32970917” or “32407438” or “32513790” or “32439468” or “33063036” or “33077677” or “32406056” or “32716821” or “32588590” or “32239757” or “32829902” or “32807521” or “32379350” or “33125767” or “32829731” or “32988821” or “32780977” or “32648633” or “32829907” or “32330635” or “32692998” or “33013067” or “33010706” or “32502292” or “32780969” or “32998780” or “32754731” or “32639607” or “32233030” or “32953429” or “32246897” or “32955802” or “32425490” or “32418270” or “32445255” or “32775945” or “32775948” or “32775953” or “32407043”).ui.152
1110 and 20191201:20301231.(dt).145,485
12exp Zygomycosis/4474
17(black fungus or black fungi).mp.192
18exp Mucorales/6616
3312 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 3214,534
3411 and 3357
Search was conducted on 9 June 2021 at 4:25 p.m. (CET).


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Figure 1. PRISMA flowchart showing study selection process.
Figure 1. PRISMA flowchart showing study selection process.
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Table 1. Summary of study characteristics and anamnestic, diagnostic, and treatment features of COVID-19-associated mucormycosis (CAM) cases.
Table 1. Summary of study characteristics and anamnestic, diagnostic, and treatment features of COVID-19-associated mucormycosis (CAM) cases.
ComorbiditiesCOVID-19 TreatmentClinical FeaturesRegionDiagnosisGenus/Species
Alekseyev et al. 2021 [31]USACase report1M41RT-PCRNRNRYesNoNoNoDKAYes (name NS)HCQNSNSNoNoYesNS
Arana et al. 2021 [32]SpainCase report1M62RT-PCRSevere (requiring non-invasive mechanical ventilation)7YesYesNoYesESKDDexamethasone 6 mg daily for 10 daysCeftriaxone, azithromycinFever, headache and left malar region swellingRhinosinusalNoYesNoRhizopus/Rhizopus oryzae
1M48RT-PCRModerate (FiO2: 28%)21NoYesNoNoESKDPrednisone 20 mgHCQ, azithromycin, lopinavir/ritonavir, tocilizumabPain and increase in right limb diameterMusculoskeletalNoYesNoLichtheimiaceae/Lichtheimia ramosa
Ashour et al. 2021 [33]EgyptCase series6M/F: 3/354.66RT-PCR (2);
NR (4)
Critical (n = 1) on ventilation;
NR (n = 5)
Not clearYes (100%)NoNoNoCKD (12.5%)NRNROphthalmoplegia (66%), conjunctival chemosis (33%), eyelid edema (33%), facial edema (33%)Rhino-orbital-cerebral (100%)NoYesYesNS
Bayram et al. 2021 [34]TurkeyCase series11M/F: 9/273.1 ± 7.7 years (range: 61–88 years)SuspectedSevere (oxygen saturation <93% in room air)14.4 ± 4.3 (range: 7–23 days)Yes (73%)Yes (64%) Yes (18%)Renal failure (45%)Dexamethasone (100%)NRProptosis (100%), ophthalmoplegia (64%), orbital pain (82%), conjunctival hyperemia or chemosis (82%), ptosis (64%), fixed and dilated pupil (64%), vision loss (64%), endophthalmitis (54.5%), and decreased vision (27%)NRYesYesYesNR
Bellanger et al. 2021 [35]FranceCase report1M55RT-PCRSevere (ICU)21NoNoNoNoFollicular lymphoma, influenza BNRNRWorsening of respiratory symptomsNRNRYesYesRhizopus/Rhizopus microsporus
Dallalzadeh et al. 2021 [36]USACase report1M48RT-PCRCritical (ICU, ventilation)6YesNoNoNoKetoacidosisDexamethasoneCCP (COVID-19 convalescent plasma)NRRhino-orbitalYesYesNoRhizopus/Rhizopus species
El-Kohly et al. 2021 * [38]EgyptCross-sectional28M/F: 19/1752.92 ± 11.30 RT-PCRMixed (mild (n = 11), moderate (n = 13), severe (n = 12))17.82 ± 2.97 Yes (27.8%)Yes (17%)Yes (8%)NoCKD (8%)Yes (name NS)Antiviral, anticoagulant, and vitamins (name NS)Headache and facial pain (75%), facial numbness (67%), ophthalmoplegia, and visual loss (64%), ophthalmoplegia (64%), diplopia (17%)Sinonasal (100%), orbital (81%), cerebral (29%), and palatine (33%)YesYesYesMucor-species
Evert et al. 2020 [70]GermanyCase series2F52.5RT-PCRCritical (n = 2 on ventilation)NRNoNoNoNoObesity, liver cirrhosisYesNRNRNRNoNoYesMucor-species
Garg et al. 2021 [39]IndiaCase report1M55RT-PCRSevere (84% SpO2)21YesYesNoNoESRD, Ischemic cardiomyopathy, venous thrombosisDexamethasone (6 mg, once a day for 14 days)Remdesivir (200 mg on day 1 and 100 mg on days 2–5); supportive careCavitary pneumonia with pleural effusionPulmonary mucormycosis/cavitary pneumonia with pleural effusionYesYesNoRhizopus/Rhizopus microsporus
Hanley et al. 2020 (Autopsy) [40]UKCase series1M22RT-PCRCritical (mechanical ventilation, vasopressor, ICU)ConcurrentNRNRNRNRFrank necrotic- hemorrhagic pancreatitis; renal failureNRNRNRNRYesNoYesNR
Johnson et al. 2021 [41]USACase report1M79RT-PCRCritical (ICU, ventilation)19YesYesNoNoPulmonary aspergillosisIV dexamethasone (6 mg daily for 10 days)IV remdesivir (200 mg × 1, then 100 mg daily)NRNRNoYes (BAL culture)YesRhizopus/Rhizopus arrhizus
Junior et al. 2020 [37]BrazilCase report1M86Throat swabSevere (ICU)ConcurrentNoYesNoNoNRHydrocortisoneOseltamivirMild abdominal tendernessNRYesNoYesNR
Kanwar et al. 2021 [42]USACase report1M56RT-PCRSevere13NoNoNoNoESRDMethylprednisoloneTocilizumabNecrotizing pneumonia with empyemaNRYesYesNoRhizopus/Rhizopus azygosporus
Karimi-Galougah et al. 2021 [43]IranCase report1F61RT-PCRNR21YesNoNoNoNRYes (name NS)Remdesivir, interferon alphaHemifacial pain, proptosis, frozen eye, complete loss of vision, and fixed mydriasisRhino-orbitalNRNRYesNR
Khatri et al. 2021 [44]USACase report1M68SuspectedCritical90YesYesNoYesSevere heart failure, obstructive sleep apnea; renal failureMethylprednisolone/Prednisone (for gout)CCPPurplish skin discoloration with fluctuant swellingCutaneousYesYesYesRhizopus/Rhizopus microsporus
Khan et al. 2020 [71]USACase report1F44RT-PCRCritical (ICU, ventilation)13YesNoNoNoNoMethylprednisolone 30 mg IV twice a dayRemdesivir 100 mg IV dailyNRPulmonary mucormycosisYesYesYesNS
Krishna et al. 2021 [45]IndiaCase report1M34RT-PCRSevereNRYesYesNoNoNRNRNRSwelling pain over the first quadrant teethSinonasalNoNoYesNR
Krishna et al. 2021 [46]UKCase report (autopsy)1M22RT-PCRSevere (mechanical ventilation)AutopsyNoNoNoNoNoYes (name NS)Meropenem and teicoplaninThrombo-emboli were seen in the lungs, brain, pharynx, nasal mucosa, and tracheaNRYesNoNoMucorales/NS
Maini et al. 2021 [47]IndiaCase report1M38RT-PCRSevere (ICU)18NoNoNoNoNOMethylprednisolone (80 mg/day)Inj. remdesivir IV with a loading dose of 200 mg, followed by 100 mg daily for 11 days.Swelling and pain in the left eyeRhino-orbital-cerebralYesYesYesRhizopus/Rhizopus oryzae
Mehta et al. 2020 [48]IndiaCase report1M60RT-PCRCritical (ICU, ventilation)11YesNoNoNoNoMethylprednisolone (40 mg twice daily) and dexamethasone (4 mg twice daily)Oseltamivir (75 mg twice daily), later tocilizumab (400 mg)Bilateral lid edema with right eye prominence, febrile, breathless, and hypoxicRhino-orbital-cerebralYesYesYesMucorales/unspecified
Mekonnen et al. 2021. [49]USACase report1M60SuspectedCritical (mechanical ventilation, ICU)4YesYesYesNoAKIDexamethasoneCCPProptosis, erythema and edema of the eyelids, and conjunctival chemosisRhino-orbitalYesYesYesRhizopus/Rhizopus species
Meshram et al. 2021 [50]IndiaCase report (renal transplant recipients)2M47; 25SuspectedMildNRYesNoNoNoNoNRNRSwelling over the face and black nasal discharge (50%); fever, cough, and black expectoration (50%)Rhino-orbito-cerebralNoYesYesNo
Mishra et al. 2021 [68]IndiaCase series10M/F: 9/155.8SuspectedMixed (mild (n = 3); moderate (n = 6); severe (n = 1))NRYes (80%)Yes (30%)NoNoCKD (20%)Yes (60%)Remdesivir (50%)Eye pain, facial pain and nasal blockNSNoNoYesNS
Moorthy et al. 2021 [51]IndiaCase series17M:15, F:254.6, 35–73 (mean, range)RT-PCRNot specifiedConcurrent (n = 4)Yes (82.73%)-14NoNoNoNoYes (100%)NSOrbital cellulitis, facial swelling, headache, proptosis, oedema of the extraocular muscles, ophthalmoplegiaSinusitis alone (n = 3), rhino- orbital (n = 6), rhino-orbital- cerebral (n = 5), rhino-cerebral (n = 3)YesNoYesMucorales/unspecified
Nehara et al. 2021 [52]IndiaCase series5M/F: 1/462.2 Average ageRT-PCRNRNRYes (100%)Yes (40%)NoNoYes (20%)DexamethasoneOxygen supplementation, intravenous meropenem, remdesivir (40%), subcutaneous enoxaparin, tablet azithromycin, basal-bolus insulin, and supportive careSevere headache, diminished vision, chemosis, mild proptosis, complete ophthalmoplegia, blackish discharge from the nasal cavity, and black crust on the hard palateRhinocerebralYesYesYesRhizopus/Rhizopus arrhizus
Pakdel et al. 2021 [53]IranCross-sectional15M: 10; F: 5Median age: 52 (14–71)RT-PCRSevere (34%)Median: 7 (1–37)Yes (87%)Yes (46%)Yes (13%)NoKetoacidosis (6%)Dexamethsaone (46%)Yes (7%)Unilateral periorbital pain and edema (73%), eyelid ptosis (73%), acute vision loss (73%), proptosis (73%), unilateral facial edema (60%), cranial nerve palsy (60%), headache (33%), fever (27%), nasal blockage (13%), and ear pain (7%)Mixed (rhinorbital (47%); sino-orbital (33%), isolated orbital movement (13%), and others)YesNoYesNS
Pasero et al. 2020 [54]Italy (renal transplant)Case report1M66RT-PCRCritical (ICU)14NoYesNoNoRenal failureNoHCQS, lopinavir, ritonavirNSNSYesYesNoRhizopus/Rhizopus species
Pauli et al. 2021 [55]BrazilCase report1F50SuspectedMild8YesNoNoNoNoHydrocortisoneNRDeep ulcerated lesion located at the center of the hard palatePalatal ulcerYesNoYesMucorales/unspecified)
Placik et al. 2020 [56]USACase report1M49RT-PCRCritical14NoNoNoNoNoDexamethasoneRemdesivir, tocilizumabNecrotizing pneumonia with bronchopleural fistulaNSYesYesYesRhizopus/Rhizopus species
Rabagliati et al. 2021 [57]ChileRetrospective cohort study1M55SuspectedCritical (ICU)Not specifiedYesYesNoYesAtrial fibrillation812 mg prednisone equivalentNoNSNSNoYesNoRhizopus/Rhizopus microsporus
Rao et al. 2021 [58]IndiaCase report1M66SuspectedNRNRNoNoNoNoNoSystematic steroidsNRComplete left ptosis and proptosis, chemosis and fixed dilated left pupil, and absence of left ocular movements in all directions of gaze, vision loss in the left eyeRhino-orbito-cerebralNoYesNoFungal hyphae
Ravani et al. 2021 [59]IndiaRetrospective cohort18NRNRRT-PCRNR60Yes (100%)NRNRNRNRDexamethasoneNRDiminution of vision (<6/60 in 81% of patients) and ophthalmoplegia (77%), orbital cellulitis (61%), pansinusitis (77%)NRNoNoYesNS
Revannavar et al. 2021 [60]IndiaCase report1FNRRT-PCRMildNot specifiedYesNoNoNoNoNRNRLeft-sided facial pain, complete ptosis and fever, tenderness of all sinuses on left side, ophthalmoplegia (left eye), left eye visual acuityNSNoYesYesRhizopus/Rhizopus species
Saldanha et al. 2021 [61]IndiaCase report1F32RT-PCRNot specifiedConcurrentYesNoNoNoNoNRNRLeft eye complete ptosis and left facial pain, visual acuity (left eye)NSNoYesYesNS
Sarkar et al. 2021 [62]IndiaCase series6M:4, F:244RT-PCRCritical (n = 6)ConcurrentYes (100%)NoNoNoKetoacidosis (33%)DexamethasoneRemdesivir (84%)Visual acquity (100%)Rhino-orbital (n = 5), rhino- orbital-cerebral (n = 1)YesYesNoRhizopus (n = 4), Mucorales (n = 2)
Satish et al. 2021 [69]IndiaCase series11NRNRRT-PCRMixed (mild (n = 2); moderate (n = 3); severe (n = 4); asymptomatic (n = 2)NRYes (100%)NoNoNoNoNRNRNRNSYesNoNoNR
Sen et al. 2021 [63]IndiaRetrospective cohort6 (5 patients post covid-19 recoved)M60.5 ± 12 (range 46.2 to 73.9) yearsRT-PCRSevereNRYes (100%)Yes (50%)NoYes (16.6%)Diabetic ketoacidosis (50%)Intravenous methylprednisolone/dexamethasone/oral prednisolone (84%)NoPain, redness, and periocular swelling, drooping of eyelids, limitation of ocular movements, and painful loss of visionRhino-orbital-cerebralNoYesYesMucorales/unspecified
Veisi et al. 2021 [64]IranCase report1F40RT-PCRMildNRNoNoNoNoNoDexamethasone (8 mg/day)Remdesivir 200 mg on day 1 followed by 100 mg daily for 4 days, and IV levofloxacin (500 mg/day),Bilateral visual loss, periorbital pain, and visual acuityRhino-orbito-cerebralNRNRYesNR
1M54RT-PCRNRNRYesNoNoNo Dexamethasone (8 mg/day)Remdesivir 200 mg on day 1 followed by 100 mg daily for 4 days, IV levofloxacin (500 mg/day)Left orbital pain and periorbital swelling together with progressive vision lossRhino-orbitalNRNRYesNR
Waizel-Haiat et al. 2021 [65]MexicoCase report1F24RT-PCRCritical (ICU)ConcurrentYesNoNoNoKetoacidosis, renal failureNANALeft lid swelling and maxillary hypoesthesia, left hyperemic conjunctiva, and an opaque corneaRhino-orbitalYesYesNoLichtheimia (Absidia) species
Werthman-Ehrenreich et al. 2021 [66]USACase report1F33SuspectedSevere (ICU)ConcurrentYesYesYesNoKetoacidosis, renal failureNoRemdesivir, CCPEye ptosisRhino-orbital-cerebralYesYesNoMucorales/unspecified
Zurl et al. 2021 [67]AustriaCase report1M53RT-PCRCritical (ICU)ConcurrentNoNoNoNoMyelodysplastic syndromes, acute myeloid leukemiaPrednisoloneTocilizumabNRFungal pneumonia with effusionYesNoYesRhizopus/Rhizopus microsporus
CAD: coronary artery disease; DM: diabetes mellitus; ESRD: end-stage renal disease; F: female; HCQs: hydroxychloroquine; HTN: hypertension; ICU: intensive care unit; IV: intravenous; M: male; NR: not reported; NS: not specified; RT-PCR: reverse-transcriptase polymerase chain reaction; USA: United States of America. * No separate outcomes reported for mucormycosis (n = 28).
Table 2. Treatment details and patient outcomes.
Table 2. Treatment details and patient outcomes.
Study (Author, Year)CountryTreatmentPatient Outcome *
Medical ManagementSurgical Management
Alekseyev et al. 2021 [31]USANRYesLived
Arana et al. 2021 [32]SpainAmphotericin B (LAmB 5 mg/kg/day), isavuconazole, and subsequently posaconazole Yes (surgical debridement)Lived
Amphotericin B (LAmB 5 mg/kg/day) together with isavuconazole 200 mg/8 h for 24 daysYes (surgical debridement)Lived
Ashour et al. 2021 [33]EgyptAmphotericin B Yes (surgical debridement (n = 4))Lived (67%),
Died (33%)
Bayram et al. 2021 [34]TurkeyAmphotericin B, voriconazoleYes (all patients: endoscopic sinus surgery with extensive debridement)Lived (36%),
Died (64%)
Bellanger et al. 2021 [35]FranceAmphotericin B (LAmB 5 mg/kg/day)NoDied
Dallalzadeh et al. 2021 [36]USAAMB/isavuconazole NoDied
El-Kohly et al. 2021 * [38]EgyptAmphotericin B; voriconazole; posaconazole Yes (endoscopic debridement (n = 27))Lived (64%),
Died (36%)
Evert et al. 2020 [70]GermanyNRNRDied (100%)
Garg et al. 2021 [39]IndiaAmphotericin B (LAmB 5 mg/kg/day)NoLived
Hanley et al. 2020 [40]UKNRNRDied
Johnson et al. 2021 [41]USAAmphotericin B (LAmB 400 mg daily)Yes (no tracheostomy, and percutaneous endoscopic gastrostomy)Lived
Junior et al. 2020 [37]BrazilNoNRDied
Kanwar et al. 2021 [42]USAAmphotericin B (LAmB 5 mg/kg/day)Yes (robotic decortication surgery)Died
Karimi-Galougah et al. 2021 [43]IranYes (not specified)Yes (endonasal endoscopic debridement of necrotic tissue, right eye exenteration)Lived
Khatri et al. 2021 [44]USAAmphotericin B + posaconazole Yes (thoracic cavity debridement) Died
Khan et al. 2020 [71]USAAmphotericin B (5 mg/kg/day) NoDied
Krishna et al. 2021 [45]IndiaAmphotericin B (LAmB 5 mg/kg/day)Yes (surgical resection)Lived
Krishna et al. 2021 [46]UKCaspofunginNoDied
Maini et al. 2021 [47]IndiaAmphotericin B 300 mg/day, tobramycin and fluconazoleYes (debridement) Lived
Mehta et al. 2020 [48]IndiaAmphotericin BNoDied
Mekonnen et al. 2021. [49]USAAmphotericin B (LAmB) + caspofungin/posaconazoleYes (sinus debridement) Died
Meshram et al. 2021 [50]IndiaAmphotericin B Yes (maxillectomy)Died
Mishra et al. 2021 [68]IndiaAmphotericin BYes ((all patients (mixed or any single surgery): functional endoscopic sinus surgery, endoscopic maxillectomy, local debridement)Lived (50%),
Died (40%),
Lost to follow-up (10%)
Moorthy et al. 2021 [51]IndiaAmphotericin B (5 mg/kg/day)Yes (FESS (n = 17), maxillectomy(n = 11), exenteration (n = 11))Died (35.29%)
Nehara et al. 2021 [52]IndiaAmphotericin B (LAmB 5 mg/kg/day), posaconazoleNoLived (60%),
Died (40%)
Pakdel et al. 2021 [53]IranAmphotericin B (LAmB 5 mg/kg/day), oral posaconazole Yes (sinus debridement (n = 12); orbital externation (n = 5); palatal debridement (n = 2))Lived (53%),
Died (47%)
Pasero et al. 2020 [54]ItalyAmphotericin B/isavuconazoleNoDied
Pauli et al. 2021 [55]BrazilAmphotericin BYes (debridement) Lived
Placik et al. 2020 [56]USAAmphotericin BYes (resection)Died
Rabagliati et al. 2021 [57]ChileAmphotericin B (LAmB)NoDied
Rao et al. 2021 [58]IndiaAmphotericin B (LAmB)Yes (endoscopic sinus surgery)NR
Ravani et al. 2021 [59]IndiaAmphotericin B (LAmB 5 mg/kg/day)Yes (sinus debridement; n = 18)Lived (94%),
Died (6%)
Revannavar et al. 2021 [60]IndiaAmphotericin BYes (endoscopic sinus surgery) Lived
Saldanha et al. 2021 [61]IndiaAmphotericin B (25 mg/day) Yes (endoscopic sinus surgery)Lived
Sarkar et al. 2021 [62]IndiaAmphotericin BYes (maxillectomy (n = 3), debridement (n = 1))Died
Satish et al. 2021 [69]IndiaAmphotericin BYes (all patients: surgical debridement) No data
Sen et al. 2021 [63]IndiaAmphotericin B (LAmB)+ voriconazole/posaconazole Yes (exenteration (n = 2), sinus debridement (n = 3))Lived
Veisi et al. 2021 [64]IranAmphotericin B (4 mg/kg/day)Yes (surgical debridement)Died
Amphotericin B (3 mg/kg/day)Yes (endoscopic sinus surgery)Lived
Waizel-Haiat et al. 2021 [65]MexicoAmphotericin BNoDied
Werthman-Ehrenreich et al. 2021 [66]USAAmphotericin BYes (sinus debridement)Died
Zurl et al. 2021 [67]AustriaNoNoDied
AMB: amphotericin B; IV: intravenous; LAmB: liposomal amphotericin B; NR: not reported; UK: United Kingdom; USA: United States of America. * No separate outcomes were reported for mucormycosis (n = 28).
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Hussain, S.; Baxi, H.; Riad, A.; Klugarová, J.; Pokorná, A.; Slezáková, S.; Líčeník, R.; Najmi, A.K.; Klugar, M. COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping. Int. J. Environ. Res. Public Health 2021, 18, 10340.

AMA Style

Hussain S, Baxi H, Riad A, Klugarová J, Pokorná A, Slezáková S, Líčeník R, Najmi AK, Klugar M. COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping. International Journal of Environmental Research and Public Health. 2021; 18(19):10340.

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Hussain, Salman, Harveen Baxi, Abanoub Riad, Jitka Klugarová, Andrea Pokorná, Simona Slezáková, Radim Líčeník, Abul Kalam Najmi, and Miloslav Klugar. 2021. "COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping" International Journal of Environmental Research and Public Health 18, no. 19: 10340.

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