A: 1
R: 5
DM: Diabetes mellitus, CNS: Central nervous system, GIT: Gastro-intestinal tract, M: Male, F: Female, T1DM: Type 1 diabetes mellitus, DKA: Diabetic ketoacidosis, NOD: New-onset diabetes, NDD: Newly detected diabetes, A: Active COVID-19, R: Recovered COVID-19, Y: Yes, N: No, HT: Heart transplant, AF: Aspergillosis fungi, LFU: Lost to follow-up, LAMA: Left against medical advice.
Characteristics of 101 patients of mucormycosis with COVID-19.
Confirmed mucormycosis, N = 101 | n, (%) | Remarks and limitations | |
---|---|---|---|
Country reported (Published) | India | 82 (81.2) | Highest cases reported from India. ≈ denotes nearest rounded of value. |
USA | 9 (8.9) | ||
Iran | 3 (≈3.0) | ||
UK | 1 (≈1.0) | ||
France | 1 (≈1.0) | ||
Italy | 1 (≈1.0) | ||
Brazil | 1 (≈1.0) | ||
Turkey | 1 (≈1.0) | ||
Mexico | 1 (≈1.0) | ||
Austria | 1 (≈1.0) | ||
Age (Years) | Range 22-86 | – | |
Sex | Male | 71/90 (78.9) | More commonly observed in males. |
Female | 19/90 (21.1) | ||
COVID-19 status | Active | 60/101 (59.4) | Exact definition of active and recovered cases of COVID-19 was different and not unanimous. |
Recovered | 41/101 (40.6) | ||
Risk factors | Hyperglycemia at presentation | 75/90 (83.3) | No unanimous definition of hyperglycemia. |
Malignancy | 3/101 (3.0) | 2 Leukemia, 1 Lymphoma | |
Post-transplant | 1/101 (1.0) | 1 Heart transplant | |
Hyperglycemia at presentation | Pre-existing DM | 72/90 (80.0) | Unless reported as insulin-dependent or type 1 diabetes, all cases were assumed as type 2 diabetes. Lack of baseline HbA1c data and duration of diabetes for majority of DM patients. |
Types of DM | – | ||
Type 2 diabetes | 70/72 (97.2) | ||
Type 1 diabetes | 2/72 (2.8) | ||
New-onset DM/hyperglycemia | 2/90 (2.2) | ||
Presented with DKA | 15/101 (14.9) | ||
Treatment history of COVID-19 | Steroid | 74/97 (76.3) | Few cases were received all 3 drugs for COVID-19. |
Tocilizumab | 4/97 (4.1) | ||
Remdesivir | 20/97 (20.6) | ||
Mucormycosis | Confirmed | 95/101 (94.1) | Confirmed denotes microbiological or histopathological diagnosis. |
Suspected | 6/101 (5.9) | ||
Location of mucormycosis | Nasal/Sinus | 80/90 (88.9) | There appears to have an overlap between Nasal/Sinus only and Rhino-orbital variety. |
Rhino-orbital | 51/90 (56.7) | ||
Rhino-orbito-cerebral | 20/90 (22.2) | ||
Bone involvement | 15/101 (14.9) | ||
Pulmonary | 8/101 (7.9) | ||
Gastrointestinal | 1/101 (1.0) | ||
Cutaneous | 1/101 (1.0) | ||
Outcomes | Alive (Improved/Improving) | 56/101 (55.4) | Outcomes is difficult to assess considering that several cases were still under in-hospital treatment and their final outcome are not yet known. |
Unchanged | 5/101 (5.0) | ||
Death | 31/101 (30.7) | ||
Status unknown (LFU, LAMA) | 9/101 (8.9) |
DM: Diabetes mellitus, DKA: Diabetic ketoacidosis, LFU: Lost to follow-up, LAMA: Left against medical advice.
Although mucormycosis is an extremely rare in healthy individuals but several immunocompromised conditions predispose it. This includes uncontrolled DM with or without DKA, hematological and other malignancies, organ transplantation, prolonged neutropenia, immunosuppressive and corticosteroid therapy, iron overload or hemochromatosis, deferoxamine or desferrioxamine therapy, voriconazole prohylaxis for transplant recipients, severe burns, acquired immunodeficiency syndrome (AIDS), intravenous drug abusers, malnutrition and open wound following trauma [ 45 ]. Mucormycosis can involve nose, sinuses, orbit, central nervous system (CNS), lung (pulmonary), gastrointestinal tract (GIT), skin, jaw bones, joints, heart, kidney, and mediastinum (invasive type), but ROCM is the commonest variety seen in clinical practice world-wide [ 45 ]. It should be noted that term ROCM refers to the entire spectrum ranging from limited sino-nasal disease (sino-nasal tissue invasion), limited rhino-orbital disease (progression to orbits) to rhino-orbital-cerebral disease (CNS involvement) [ 46 ]. The area of involvement may differ due to underlying condition. For example, ROCM is frequently observed in association with uncontrolled diabetes and DKA, whereas pulmonary involvement is often observed in patients having neutropenia, bone marrow and organ transplant, and hematological malignancies, while GIT gets involved more in malnourished individuals. Giant cell invasion, thrombosis and eosinophilic necrosis of the underlying tissue is the pathological hallmark of mucormycosis. Microbiological identification of the hyphae based on diameter, presence or absence of septa, branching angle (right or acute branching), and pigmentation, differentiates it from other fungal infections. The 1950 Smith and Krichner [ 47 ] criteria for the clinical diagnosis of mucormycosis are still considered to be gold standard and include:
A 2019 nationwide multi-center study of 388 confirmed or suspected cases of mucormycosis in India prior to COVID-19, Prakash et al. found that 18% had DKA and 57% of patients had uncontrolled DM [ 48 ]. Similarly, in a data of 465 cases of mucormycosis without COVID-19 in India, Patel et al. [ 49 ] has shown that rhino-orbital presentation was the most common (67.7%), followed by pulmonary (13.3%) and cutaneous type (10.5%). The predisposing factors associated with mucormycosis in Indians include DM (73.5%), malignancy (9.0%) and organ transplantation (7.7%) [ 49 ]. Presence of DM significantly increases the odds of contracting ROCM by 7.5-fold (Odds ratio 7.55, P = 0.001) as shown in a prospective Indian study, prior to COVID-19 pandemic [ 50 ]. In a recent systematic review conducted until April 9, 2021 by John et al. [ 51 ] that reported the findings of 41 confirmed mucormycosis cases in people with COVID-19, DM was reported in 93% of cases, while 88% were receiving corticosteroids. These findings are consistent with our findings of even larger case series of 101 mucormycosis cases (95 confirmed and 6 suspected) in Covid-19, where 80% cases had DM, and more than two-third (76.3%) received a course of corticosteroids. Collectively, these findings suggest a familiar connection of mucormycosis, diabetes and steroid, in people with COVID-19.
Since there are no studies that compared patients of mucormycosis in non-diabetic COVID-19 who did not receive steroids versus COVID-19 patients who received steroids and developed mucormycosis, it is difficult to establish a causal effect relationship between COVID-19 and mucormycosis in relation to corticosteroids. Nonetheless, there appears to be a number of triggers that may precipitate mucormycosis in people with COVID-19 in relation to corticosteroids:
Fig. 1 depicts the postulated mechanism of increased propensity of having mucormycosis infection in COVID-19 patients.
Postulated interaction of diabetes, corticosteroid and COVID-19 with mucormycosis.
There are certain limitations to conduct this kind of systematic review based on case reports/series subject to publication biases and considerable heterogeneity in reporting cases. It is highly likely that reported cases of mucormycosis may be an underrepresentation of the real burden owing to difficulty in making a microbiological or histopathological diagnosis especially in a raging pandemic setting. While some case reports had every minute detail, other did not report important parameter, for example – duration of DM, lack of baseline HbA1c data in majority of cases. Secondly, the lack of a denominator value may not allow the true estimation of mucormycosis incidence in people with COVID-19 compounded by the lack of control. Thirdly, defining active and recovered COVID-19 and its relation to the onset of mucormycosis could be difficult considering the lower sensitivity of confirmatory RT-PCR. Finally, evaluating the outcomes in people with mucormycosis and COVID-19 could be difficult at the moment because these case reports have been published while many of these patients are still under treatment. Other minor limitations have been highlighted in Table 2 .
Increase in mucormycosis in Indian context appears to be an unholy intersection of trinity of diabetes (high prevalence genetically), rampant use of corticosteroid (increases blood glucose and opportunistic fungal infection) and COVID-19 (cytokine storm, lymphopenia, endothelial damage). All efforts should be made to maintain optimal hyperglycemia and only judicious evidence-based use of corticosteroids in patients with COVID-19 is recommended in order to reduce the burden of fatal mucormycosis.
No funding.
AKS conceptualized, searched the literature and wrote first draft; RS made the tables, analyzed the data and revised the first draft, SRJ and AM edited the final draft. All authors agreed mutually to submit for publication.
All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship and take responsibility for the integrity of the work. They confirm that this paper will not be published elsewhere in the same form, in English or in any other language, including electronically.
We hereby declare that we have no conflict of interest, related to this article titled “Mucormycosis in COVID-19: A Systematic Review of Cases Reported Worldwide and in India”.
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2.1. Incidence of Mucormycosis. The incidence of mucormycosis is increasing [3,5,15,16,17].The exact incidence/prevalence is not known because there are few population-based studies [3,15,18], and they differ in capture periods, populations and definition or diagnostic procedures.In the study performed in the San Francisco Bay area, from 1992 to 1993, the annual incidence of mucormycosis was ...
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Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 ...
Epidemiology and host factors. Mucorales are ubiquitous fungi usually found in soil, decaying organic matter, compost and contaminated foods. Mucormycosis is considered a rare infection - diabetes remains the most prominent underlying medical comorbidity in infected patients, and was identified as an independent risk factor for rhino-orbital-cerebral mucormycosis in a meta-analysis of 851 ...
Mucormycosis frequently infects the sinuses, brain, or lungs. While infection of. the oral cavity or brain are the most common forms of mucormycosis, the. fungus can also infect other areas of the ...
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Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals, but promise is brought by RNAi and CRISPR/Cas9 approaches. Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with Rhizopus, Mucor, and Lichtheimia, accounting for > 90% of all cases. MCR is seen in patients with ...
Mucormycosis is an angioinvasive fungal infection, due to fungi of the order Mucorales. Its incidence cannot be measured exactly, since there are few population-based studies, but multiple studies have shown that it is increasing. The prevalence of mucormycosis in India is about 80 times the prevalence in developed countries, being approximately 0.14 cases per 1000 population.
This review provides an update on mucormycosis management. The latest recommendations strongly recommend as first-line therapy the use of liposomal amphotericin B (≥5mg/kg) combined with surgery whenever possible. Isavuconazole and intravenous or delayed-release tablet forms of posaconazole have remained second-line.
Abstract. Mucormycosis is a deadly opportunistic disease caused by a group of fungus named mucormycetes. Fungal spores are normally present in the environment and the immune system of the body prevents them from causing disease in a healthy immunocompetent individual. But when the defense mechanism of the body is compromised such as in the ...
Mucormycosis is caused by ubiquitous environmental moulds with a global distribution, including the Rhizopus, Apophysomyces, Mucor, and Lichtheimia species. Although generally harmless to an immunocompetent host, the infection can be deadly in patients with an impaired immune system, such as in those with haematological malignancies or poorly controlled diabetes, or in individuals receiving ...
Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, …
settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified. Introduction Suspected mucormycosis requires urgent intervention,
Mucormycosis is an angio invasive infection that occurs due to the fungi mucorales. It is a rare disease but increasingly recognized in immunocompromised patients. It can be categorized into rhino ...
Mucormycosis is a potentially lethal mycosis caused by filamentous fungi of the subphylum Mucoromycotina [1, 2].Fungi in the subphylum Mucormycotina are saprophytic fungi that are ubiquitous in nature [2, 3].They are frequently isolated from decaying organic material, soil, and compost piles [].Human infection follows the inhalation of fungal spores, traumatic inoculation, and consumption of ...
Mucormycosis is a new angioinvasive infection cau sed by the ubiquitous filamentous fungus of th e Mucorales order of the Zygomycete class. Mucormycosis. has emerged as the third most prevalent ...
Bibliometric research evidence on mucormycosis can be found in two recent publications. Dubey and Sharma (2021) presented a post-covid mucormycosis research status by analyzing only forty-one documents. The limitation of the study can be observed in less publications, and the study is limited to mucormycosis associated with COVID-19.
Mucormycosis is an angioinvasive disease that is characterized by tissue infarction and necrosis. It is an insidious fungal infection caused by members of the zygomycotic and Mucorales species. It ...
IJCRT2208050 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org a401 Mucormycosis Mrs. Dhivya.R, M.sc (Nursing), Sree balaji college of nursing, Bharath university,Chrompet, chennai, Tamilnadu, India ABSTRACT Mucormycosis is an angio invasive infection that occurs due to the fungi mucorales. It is a rare disease
Mucormycosis is an infection caused by fungi belonging to the order Mucorales [].Rhizopus oryzae is the most common organism isolated from patients with mucormycosis and is responsible for ∼70% of all cases of mucormycosis [2-4].The major risk factors for mucormycosis include uncontrolled diabetes mellitus in ketoacidosis, other forms of metabolic acidosis, treatment with corticosteroids ...
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Papers published in any language between December 1, 2019, to June 1, 2021, were included. The literature was searched using keywords of [(COVID 19 OR Coronavirus OR corona) AND (mucormycosis OR mucor)]. The EndNote database was used from importing and managing abstracts and full texts. After first evaluation of the paper, duplicates were removed.
Results. Overall, 101 cases of mucormycosis in people with COVID-19 have been reported, of which 82 cases were from India and 19 from the rest of the world. Mucormycosis was predominantly seen in males (78.9%), both in people who were active (59.4%) or recovered (40.6%) from COVID-19. Pre-existing diabetes mellitus (DM) was present in 80% of ...