1. INTRODUCTION
In entire India, COVID-19 cases due to double mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus were jumping up in an uncontrolled manner, and the country was also imagining the fear of third COVID-19 wave. In inclusion to these calamities, India was also facing the rising cases of COVID-19 linked mysterious infection “mucormycosis” creating significantly more complications in COVID-19 patients [1–7].
In the year 2021, during the second wave of COVID-19 (SWCOVID-19), 10–100 number of the COVID-19 patients in India were getting infected with fungal co-infection mucormycosis, causing eye damage, facial deformities, blindness, and further death in severe conditions like diabetes [8–10]. News media reported the various cases of mucormycosis among the SWCOVID-19 patients from Pune, Gujarat, Ahmedabad, Madhya Pradesh, Odisha, Karnataka, Uttarakhand, Telangana, Madhya Pradesh, and Bihar [11,12]. With this inclusion, total number of cases was rising continuously in India [13–20] (Table 1).
Mucormycosis is an acute angio-invasive infection [21–23] causing embolism and death of tissues [24,25]. In most of the cases, the infection progresses as a nosocomial infection [26–34]. Mucormycosis fungus enters inside the body through environmental routes by inhalation [35–38] and captures the broad range of immunologically compromised, and immunocompetent traumatic wound patients [39–41]. Mucormycosis is caused by a group of opportunistic mold “mucoromycetes” [42], belonging to the order “Mucorales,” subphylum mucoromycotina (formerly known as class zygomycetes) [41,43]. The reported number of genera and species of mucormycosis causing infections to humans are 11 and 27, respectively, of which Rhizopus rhizome or, Mucor lichtheimia, Apophysomyces, Cunninghamella, Saksenaea, Cokeromyces, Actinomucor, and Syncephalastrum species are usually over the globe [21,22,41,44]. The Rhizopus spp were predominant in most mucormycosis infections in India. Although, Apophysomyces elegans, Anabaena variabilis, and Rhizopus homothallic were also increasing along with atypical species like Mucor irregularis and Thamnostylum lucknowense [45,46]. Mucormycosis is categorized into cerebral, cutaneous, rhino-cerebral, gastrointestinal, pulmonary, and disseminated type based on appeared anatomic localization, and clinical symptoms which are uncommon and rare [21,41,47,48].
 | Table 1: Rising mucormycosis cases in India during the second wave of COVID-19 diseases. [Click here to view] |
The causative agent of mucormycosis is omnipresent fungi predominant in dust, decaying matter which causes infrequent opportunistic communicable disease within a very short time [33]. In mucormycosis, infection macrophages and neutrophiles perform an important task in the host defense process [49–52]. When their activity gets diminished, spores germinate inside the host [53]. After the entry of fungus, spore germination gets retarded by phagocytic activity of macrophages by killing the hyphae [49]. In a normal host, during the development of infection, neutrophilic cells are attracted toward hyphae by the chemotaxis process and, attaches to it, and prevents the spread of infection. In diabetic patients, neutrophils activity gets hampered, and the long-term neutropenic condition is responsible for the evolution of disease [49].
During the SWCOVID-19-linked mucormycosis (SWCOVID-19), the mortality rate of mucormycosis patients was nearly 50% [7]. In earlier reports, death percent owing to mucormycosis in India was mentioned between 28% and 52% [22,54–59]. In a computer-model-based study, 14 mucormycosis cases per 100,000 individuals in India were evaluated [59], showing the death percent 38.2 per year [58,60]. The figures provided by this model shown ubiquity of mucormycosis in India was almost 70% greater than the global data per 100,000 persons [58]. Chander et al. [61] mentioned the altogether mortality rate of mucormycosis can be diversified by the status of the case, kind of fungal attack, affected part of the body, and adequate antifungal treatment along with surgical intervention [61]. The important reason for the death of mucormycosis-infected patients was late diagnosis [62], and old of age patients. The involvement of the head and trunk increases the number of deaths of mucormycosis [63]. It was reported, altogether death rate can fall up to 40% with antifungal treatment, and surgical debridement [64].
In this paper, we have discussed the most possible causes of mucormycosis co-infection and its severity linked to the second wave of COVID-19 patients in India.
2. RISK FACTORS FOR MUCORMYCOSIS CO-INFECTION
Mucormycosis is an opportunistic fungal infection that is generally non-pathogenic in immunocompetent persons [65,66], except in severe diabetes condition [41]. The danger of this infection is more in patients with diabetes mellitus, immunosuppressed [64,67–72], neutropenic condition [68,71,73], cancer, previously open wound Mucorales infection [73], renal failure, organ transplant, under immunosuppressive therapy, cirrhosis, acquired immune deficiency syndrome, iron overload patients, and voriconazole treatment [41,21,22,74] (Fig. 1). Some reports also mentioned infection of mucormycosis to some atypical areas of the body like: breast [75], ear [22], heart [76,77], and bone infection [78,79].
2.1. Mucormycosis and Diabetes
In the recent outbreak of mucormycosis in India among the SW-COVID-19 patients, diabetes mellitus was one of the important risk factors responsible for an increased number of cases [19,80–84]. According to the various reports, globally, among the fungal infection cases in COVID-19 recovered patients, 94% was Diabetes mellitus, and of this 71% cases was from India [5,19]. Diabetic mellitus and diabetes ketoacidosis are the frequent cause of rhino-orbital or rhino-cerebral mucormycosis [85–90], whereas the neutropenic condition of the patients is the reason for pulmonary mucormycosis [91,92]. In the Indian diabetic population pulmonary mucormycosis is the second commonest type of invasion [51,91,93], then cutaneous [22,59] and renal mucormycosis [60]. The available reports also shown, uncontrolled diabetic mellitus is the main risk factor responsible for mucormycosis infection [51,59,94–96]. These patients particularly progress into rhino-orbital mucormycosis, and rarely develop pulmonary and disseminated mucormycosis [97–99]. In a diabetic patient, fungal spores enter through the sinus, and process up to the periorbital region, face, and brain [47]. In Rhino-orbital mucormycosis infection, primary symptoms are either sinusitis or periorbital cellulitis [101], which involves trouble in eyes and face, numbness of the face, followed by conjunctival suffusion, blurry eyesight, and swelling on soft tissue [97,102,103], and blindness. Kasper et al. [100] reported in diabetes acidosis and non-ketoacidosis patients, there is a direct connection between high sugar concentrations with mucormycosis infection.
Various study reports have been published regarding the mechanism of establishment of mucormycosis infection in diabetes mellitus cases. In these patients, neutrophils activity gets reduced [50], and also patient becomes deficient in CD4 cells [104,105]. Low activity of cytokine and malfunction of polymorphonuclear cells (PMNC) may be linked with deficiency of CD4 cells [104,106]. In an individual with diabetes mellitus, triggering of microbial infection reduces the secretion of interleukin (IL)-1 & IL-6 by mononuclear cells and monocytes, which is linked to an inherent fault in the cells [106,107]. Although, according to other reports, in diabetes mellitus cases, glycation results in inhibition of production of IL-10, gamma interferon, and tumor necrosis factor. In these patients, increased glucose-6-phosphate level boosts the apoptosis of PMNC which results in a reduction in number, and their transfer through endothelial cell [107]. In diabetes ketoacidosis condition, acidosis of patient interrupts transferrin-ion binding-mechanism, which increases the number of unbound irons, and is responsible for the growth of fungi [108,109].
2.2. The Link between Mucormycosis Infection and SWCOVID-19
COVID-19 is a disease caused by the SARS-CoV-2 virus, showing a broad range of medical complications, which spreads from human–human by respiratory droplets [110]. SARS-CoV-2 virus infects the pulmonary tissues causing alveolar-interstitial lesion, which may be responsible for more susceptibility of COVID-19 patients to mucormycosis co-infection. In such cases, primarily portal of entry of fungus is through nasal route and lung airways [78,111].
During the SWCOVID-19, mucormycosis outbreak in India, all the cases of mucormycosis co-infection were COVID-19 recovered, or near to recovery patients. In COVID-19 disease, immune system of the patient gets weaken on account of virus replication and lung damage, furthermore uncontrolled diabetes mellitus, use of immunosuppressive drugs [80–83,112], comorbidity, and malnutrition also contribute to it (Fig. 1). Therefore, the vulnerability of mucormycosis co-infection is more in the case of COVID-19 disease [113], which is potentially responsible for further health complications, and also death in many cases [114]. It was found that among the 10%–30% of co-infections in hospitalized and critically ill COVID-19 patients, the fungus was ten times more frequent causative agent [115]. The greater risk factors for mucormycosis fungal co-infection in COVID-19 patients was owing to: use of immunosuppressive medications, lack of a diagnostic specific test for the incidence of fungal infections in COVID-19 patients [116], diabetes, hematologic malignancies, prolonged neutropenia, allogeneic hematopoietic stem cell transplantation, solid organ transplant [117], and long-term lymphopenia [113,118].
In COVID-19 disease, replication of virus triggers plenty of cytokines called “cytokine storm,” showing an inflammatory reaction, and extensive damage to the lung [112,119]. Such immunosuppressive state of immune system leads to an uncontrolled reduction in CD4+ and CD8+ cells [19,119–122], B-lymphocytes, and natural killer cells [123,124]. It was also reported that, SARS-CoV-2 infection also decreases the monocytes, eosinophils, and basophils count in patients [125,126]. Such acute lung tissue damage may be prone to secondary infections after the outset of COVID-19 disease [121,127–129].
In COVID-19 in diabetic patients, the mortality can be directly linked with diabetes mellitus. In SARS-CoV-2 infection, there is increased activity of angiotensin-converting enzyme-2-receptors present on pancreatic islet cells, as well as an excess of cytokines secretions generates insulin resistance creating hyperglycemic condition [130].
In COVID-19 patients, iron metabolism is also altered [131]. In severe COVID-19 cases, ferritin level increases, which conducts extra intracellular iron, generating reactive oxygen which damages the tissue. Because of severe infection and diabetic acidoketosis, cytokines particularly IL-6 activate ferritin production, which results in intracellular iron overload [131], and creates an acidic stage, responsible for the risk of mucormycosis [132].
2.3. Mucormycosis and Therapeutic Drug in COVID-19 Disease
During the SWCOVID-19, most of the COVID-19 patients in India were treated with steroids (Tocilizumab), antiviral drugs (Remdesivir), antiparasitic drug (Ivermectin), and antibiotics (Azithromycin, Doxycycline); which were also the important cause of mucormycosis [81,113,133]. The steroidal drug and antiviral drugs suppress the immune system of patients during the treatment. The steroidal drugs increase the susceptibility of patients to mucormycosis infection [134], by reducing the activity of macrophages and neutrophiles [86], there upon is an important link between COVID-19 disease and mucormycosis co-infection.
 | Figure 1: Important factors responsible for mucormycosis infection in COVID-19 and non-COVID-19 patients. [Click here to view] |
Steroids were broadly used in many COVID-19 pneumonia cases, but their efficacy for this disease has been inconsistent [135]. In case of acute pneumonia, sepsis, or critical illness, the hypothalamic–pituitary–adrenal axis gets activated and gives the inflammatory reaction. Steroidal drugs suppress the hypothalamic–pituitary–adrenal axis and develop a hypercortisolism producing endogenous cortisol [136], which reduces lung damage by controlling the various inflammatory responses [135]. In COVID-19 patients, this drug prevents the damage of the lung by reducing the inflammation but increases the blood sugar in both diabetic and non-diabetic, and immunologically weak patients.
In case the high dose of steroid induces hypercortisolemia condition, which liberates corticotropin-releasing hormone and adrenocorticotropic hormone, causes succeeding hypocortisolemic state [137]. According to one report, the overall mortality rate of mucormycosis was 50%, and this was probably due to the use of the steroidal drug to save critical COVID-19 patients. In the case of COVID-19 diseased patients, therefore appropriate steroid doses are important [114,138].
Antiviral medicines are also used to treat COVID-19 patients. Antiviral medicine like ritonavir inhibits cytochrome P450 3A4 (CYP3A4) strongly, and thereupon during the treatment, there may be chances of incidence of Adrenal insufficiency [139]. Adrenal insufficiency is linked with depleted function of natural killer cells which is important for recognizing infectious agents, and may be responsible for mucormycosis co-infection. During the treatment, sudden termination of steroidal drug which is particularly associated with ritonavir could be dangerous for incentive care unit’s cases as it promotes hypocortisolemic state. Even so another blend of treatments like hydroxychloroquine, antiviral could create a hypocortisolemic state [139].
2.4. Mucormycosis and Malnutrition
Malnutrition is also one of the factors for opportunistic co-infections. Earlier work mentioned in literature suggests that patients who stay longer in an intensive care unit (ICU) develop a loss of appetite. In COVID-19, malnutrition gets provoked during the long-time hospital stay in ICU, responsible for the slow recovery of patients [140]. Therefore, nutritional deficiencies have been noticed over all the stages of COVID-19, especially in serious patients [141].
2.5. Mucormycosis and Other Risk Factors
According to a news report in late May 2021, excessive use of food supplement zinc may also be one of the factors for mucormycosis co-infection in India [142,143]. Zinc is a supplement used to boost immunity in nutrient-deficient patients. But there is no proof that zinc prevents or treats COVID-19[144]. Further investigation is required to support this data.
3. DISCUSSION
During the SWCOVID-19 in India, COVID-19 patients were started to acquire a deadly opportunistic fungal infection called mucormycosis. The number of mucormycosis cases was increasing with great speed in 28 states of India, of which 86% were history of COVID-19, and 62.3% were history of diabetes [20], exhibiting symptoms of visual changes, nasal stuffiness, facial fullness, headache, blindness, and even death of the patients [10,80].
There were several factors that increased the extremity of mucormycosis in COVID-19 patients than non-COVID-19 patients [145–147]. The main factors responsible for this infection in near recovery and recovered COVID-19 patients were diabetes mellitus and diabetes ketoacidosis [20,80–84,148], critical illness, long-term ventilation, hospital stay [135,139], treatment with the immunosuppressive steroidal drug, an antiviral drug, and other drugs [80,112,135,139]. During the COVID-19 infection, increased viral load in patients elevates the activity of cytokines, called “cytokine storm” which comprehend the danger and projection of the disease [149]. This cytokine supplies inflammatory monocytes with the elevated synthesis of inflammatory cytokines like IL-6 [150]. This inflammation-causing cells enter into the lungs and cause lung injury which is responsible for trouble in lung function of COVID-19 cases [151]. In such COVID-19 patients, susceptibility to opportunistic fungal co-infections like mucormycosis increases.
Patients with uncontrolled diabetes, chances of mucormycosis fungal infections are high [5,20]. In case of uncontrolled diabetes, increased sugar level of patients supports the growth of fungus by at least three channels; (1) hyper glycation of iron-sequencing proteins, (2) overexpression of mammalian cell receptor (glucose regulate protein GRP78) which binds to Mucormycosis fungus, (3) evocation of poorly distinguished fault in phagocytosis [100].
During the COVID-19 disease, treatment with immunosuppressive steroidal drugs prevents lung inflammation by hampering the function of macrophages and neutrophils, but these drugs also suppress the natural immune defense mechanism of patients [85,135]. Therefore, diabetes mellitus and inappropriate dose of steroids were the most important link for the risk of mucormycosis in India [81]. During the long-time hospital stay, the condition of ventilators for adequate oxygen supply also increases the susceptibility of COVID-19 patients towards this opportunistic fungal co-infection mucormycosis (Fig. 2).
During the SWCOVID-19, the new variant was more infective [152] than the previous variants of COVID-19. Along with this severe lung damage due to overexpression of immune system, diabetic condition of the patients, use of immunosuppressive drugs (Fig. 2), hospital environment, and condition of a ventilator have increased the rise in susceptibility and mortality of mucormycosis cases in India. The other factors that may also be responsible for mucormycosis in SWCOVID-19 patients were malnutrition, excessive use of zinc supplements (further study is required).
To prevent the outbreak of mucormycosis, the Government of India issued some guidelines for screening, diagnosis, and management of mucormycosis [153]. All India Institute of Medical Science (AIIMS) doctors advised homecare patients not to take antiviral drug [154]. The Union Health Ministry and Family Welfares’ Directorate General of Health Services (DGHS) had issued the guidelines to stop the use of Ivermectin and doxycycline in COVID-19 patients [155], and also removed Ivermectin, azithromycin, doxycycline, zinc, favipiravir, and plasma therapy from recommendation list [156,157].
 | Figure 2: A risk factor in mucormycosis disease. [Click here to view] |
4. CONCLUSION
Mucormycosis is an opportunistic fungal infection. The rising cases of COVID-19 linked mucormycosis in many states of India may be related to one or more factors. In SWCOVID-19 disease, severity of infection was more than the earlier COVID-19 disease, which was one of the causes for opportunistic infections like mucormycosis. Secondly, the COVID-19 sufferer who had uncontrolled diabetes mellitus, hypertension, and comorbidity was more prone to mucormycosis infection due to various hyper mechanisms in patients. Thirdly, treatment with immunosuppressive steroidal drugs in critically ill COVID-19, and other COVID-19 patients was one of the reasons for mucormycosis co-infection. To prevent these complications, unnecessary use of steroidal drug should be avoided. In the case of critically ill COVID-19 patients, the right dose and duration of steroidal drug should be used. The other drugs in COVID-19 treatments also contribute to immunosuppressive condition among COVID-19 patients, and mucormycosis infection. The diabetes mellitus COVID-19 patients already suffer from lots of complications due to COVID-19 disease, and treatment with inappropriate steroidal dose and other drugs further suppresses the immune system of patients during the recovery. These were the major links for life-threatening mucormycosis infection in India. Apart from this, malnutrition in under-recovery and recovered COVID-19 patients is very common, which weakens the immune system, can also be the reason for mucormycosis co-infection.
All the above factors are linked with each other for the severity of mucormycosis in SWCOVID-19 patients than non-COVID-19 patients. AIIMS and DGHS have issued various guidelines to prevent the new SWCOVID-19 patients from the danger of mucormycosis co-infection. However, already infected and suspected mucormycosis cases can be protected by: early diagnosis of fungus, an adequate dose of the antifungal drug (Amphotericin B) and other drugs, control over the hyperglycemic condition, maintaining oxygen level of patients, and proper diet.
5. ACKNOWLEDGMENT
The authors are thankful to the Management of Vidyabharti College, Seloo, District Wardha, Maharashtra, India, and Rajesh Dhakane, Jayawantrao Sawant College of Science and Commerce, Hadapsar, Pune, Maharashtra, India for their valuable support.
6. AUTHOR CONTRIBUTIONS
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. All the authors are eligible to be an author as per the international committee of medical journal editors (ICMJE) requirements/guidelines.
7. FUNDING
There is no funding to report.
8. CONFLICT OF INTEREST
There is no conflict of interest.
9. ETHICAL APPROVALS
This study does not involve experiments on animals or human subjects.
REFERENCES
1. BBC.com. Mucormycosis: the ‘black fungus’ maiming Covid patients in India. Available via https://www.bbc.com/news/world-asia-india-57027829 (Accessed 9 May 2021).
2. Dnaindia.com. Deadly black fungus or mucormycosis on rise in India; Rare fungal infection found in COVID-19 patients. Available via https://www.dnaindia.com/india/video-deadly-black-fungus-or-mucormycosis-on-rise-in-india-rare-fungal-infection-found-in-covid-19-patients-2889852 (Accessed 11 May 2021).
3. Timesofindia.indiatimes.com. Mucormycosis symptoms: how to identify signs and symptoms of mucomycosis, Aka black fungus infection in COVID cases? Available via https://timesofindia.indiatimes.com/life-style/health-fitness/health-news/coronavirus-black-fungus-how-to-identify-signs-and-symptoms-of-mucormycosis-aka-black-fungus-infection-in-covid-cases/photostory/82567426.cms?picid=82567607 (Accessed 12 May 2021).
4. Financialexpress.com. Black fungus: cases of post-covid mucormycosis rising. Available via https://www.financialexpress.com/lifestyle/health/black-fungus-cases-of-post-covid-mucormycosis-rising/2252641/ (Accessed 16 May 2021).
5. Indiatoday.in. Covid 19: mucormycosis or black fungus cases reported in several states in India. Available via https://www.indiatoday.in/india/video/covid-19-mucormycosis-or-black-fungus-cases-reported-in-several-states-of-india-1803076-2021-05-16 (Accessed 16 May 2021).
6. Wionews.com. Black fungus infections on the rise in India. Available from: https://youtu.be/2ykmpigRp-c (Accessed 20 May 2021).
7. Edition.cnn.com. They recovered from Covid, only to die of ‘black fungus’. What we know about the disease sweeping India. Available via https://edition.cnn.com/2021/05/21/india/black-fungus-mucormycosis-covid-explainer-intl-hnk/index.html (Accessed 24 May 2021).
8. Indiatoday.in. New Delhi: black fungus detected in Covid-19 survivors; 8 lose eyesight in Surat. Available via https://www.indiatoday.in/coronavirus-outbreak/story/black-fungus-mucormycosis-detected-covid19-survivors-8-lose-eyesight-surat-fungal-infection-symptoms-1799971-2021-05-07 (Accessed 7 May 2021).
9. Moneycontrol.com. Mucormycosis fungal infections maiming COVID-19 survivors in India: all you need to know about this ‘black fungus’. Available via https://www.moneycontrol.com/news/india/mucormycosis-fungal-infections-maiming-covid-19-survivors-in-india-all-you-need-to-know-about-this-black-fungus-6871551.html (Accessed 10 May 2021).
10. MyGov India. Mucormycosis. Available via https://youtu.be/eA5FM_2H6_A (Accessed 13 May 2021).
11. Timesofindia.indiatimes.com. Explained: mucormycosis aka black fungus in Covid-19 patient Available via https://timesofindia.indiatimes.com/india/explained-what-is-mucormycosis-aka-black-fugus-affecting-covid-19-patients/articleshow/82517866.cms (Accessed 11 May 2021).
12. Timesofindia.indiatimes.com. AIIMS to develop guidelines to treat black fungus. Available via http://timesofindia.indiatimes.com/articleshow/82731440.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst (Accessed 18 May 2021).
13. Zeebiz.com. Mumbai Zeebiz Web Desk: Black fungus alert! Center directs state government to declare mucormycosis as an epidemic. Available via https://www.zeebiz.com/india/news-black-fungus-alert-centre-directs-state-governments-to-declare-mucormycosis-as-an-epidemic-157041 (Accessed 20 May 2021).
14. Timesofindia.indiatimes.com/. 5500 cases, 126 life lost: black fungus stalk states, Maharashtra worst hit. Available via http://timesofindia.indiatimes.com/articleshow/82813528.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst (Accessed 21 May 2021).
15. Livemint.com. Black fungus: three states account for nearly 60% of mucormycosis cases in India. Available via http://livemint.com/news/india/black-fungus-gujarat-maharashtra-andhra-3-states-account-for-nearly-60-of-mucormycosis-cases-in-india-11621664559576.html (Accessed 22 May 2021).
16. Livemint.com. Black fungus: these 5 states account for over 65% of India’s 11,717 mucormycosis cases. Available via https://www.livemint.com/news/india/black-fungus-these-5-states-account-for-60-of-india-s-11-700-mucormycosis-cases-11622018575067.html (Accessed 26 May 2021).
17. Indianexpress.com. Nagpur and Pune account for almost 33% of Maharashtra’s mucormycosis cases. Available via https://indianexpress.com/article/cities/pune/nagpur-pune-account-for-almost-33-of-maharashtras-mucormycosis-cases-7344411 (Accessed 5 June 2021).
18. Medicalnewstoday.com. “Black fungus” and COVID-19: Myths and facts. Available via https://www.medicalnewstoday.com/articles/black-fungus-and-covid-19-myths-and-facts (Accessed 18 May 2021).
19. BBC.com. Black fungus: is diabetes behind India’s high number of cases. Available via https://www.bbc.com/news/world-asia-india-57252077 (Accessed 6 June 2021).
20. Livemint.com. Black fungus: these two states account for nearly 42% of India’s 28,252 mucormycosis cases. Available via https://www.livemint.com/news/india/black-fungus-28-states-see-28-252-mucormycosis-cases-maharashtra-gujarat-among-worst-hit-states-11623069135171.html (Accessed 7 June 2021).
21. 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;25(1):26–34; doi:10.1016/j.cmi.2018.07.011
22. 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;57(4):395–402; doi:10.1093/mmy/myy060
23. Bakshi SS. Rhino-orbital mucormycosis. Bull Emerg Trauma 2019;7(1):88–9; doi: 10.29252/beat-0701015
24. Kohn R, Hepler R. Management of limited rhino-orbital mucormycosis without exenteration. Ophthalmology 1985;92(10):1440–4; doi:10.1016/s0161-6420(85)33844-7
25. Frater JL, Hall GS, Procop GW. Histologic features of Zygomycosis: emphasis on perineural invasion and fungal morphology. Arch Pathol Lab Med 2001;125(3):375–8; doi:10.5858/2001-125-0375-HFOZ
26. Cohen-Abbo A, Bozeman PM, Patrick CC. Cunninghamella infections: review and report of two cases of Cunninghamella pneumonia in immunocompromised children. Clin Infect Dis 1993;17(2):173–7; doi:10.1093/clinids/17.2.173
27. Mooney JE, Wanger A. Mucormycosis of the gastrointestinal tract in children: report of a case and review of the literature. Pediatr Infect Dis J 1993;12(10):872–6; doi:10.1097/00006454-199310000-00013
28. Craig NM, Lueder FL, Pensler JM, Bean BS, Petrick ML, Thompson RB, et al. Disseminated Rhizopus infection in a premature infant. Pediatr Dermatol 1994;11(4):346–50; doi:10.1111/j.1525-1470
29. Lueg EA, Ballagh RH, Forte V. Analysis of a recent cluster of invasive fungal sinusitis at the Toronto Hospital for Sick Children. J Otolaryngol 1996;25(6):366–70.
30. Gokcil Z, Odabasi Z, Kutukcu Y, Umudum H, Vural O, Yardim M. Rhino-orbito-cerebral mucormycosis. J Neurol 1998;245(10):689–90; doi:10.1007/s004150050269
31. Darrisaw L, Hanson G, Vesole DH, Kehl SC. Cunninghamella infection post bone marrow transplant: case report and review of the literature. Bone Marrow Transplant 2000;25(11):1213–6; doi:10.1038/sj.bmt.1702395
32. Gaziev D, Baronciani D, Galimberti M, Polchi P, Angelucci E, Giardini C, et al. Mucormycosis after bone marrow transplantation: report of four cases in thalassemia and review of the literature. Bone Marrow Transplant 1996;17(3):409–14.
33. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13(2):236–301; doi:10.1128/CMR.13.2.236
34. Melsom SM, Khangure MS. Craniofacial mucormycosis following assault: an unusual presentation of an unusual disease. Australas Radiol 2000;44(1):104–6; doi:10.1046/j.1440-1673.2000.00751.x
35. Krasinski K, Holzman RS, Hanna B, Greco MA, Graff M, Bhogal M. Nosocomial fungal infection during hospital renovation. Infect Control 1985;6(7):278–82; doi:10.1017/s0195941700061750
36. Kontoyianis DP, Vartivarian S, Anaissie EJ, Samonis G, Bodey GP, Rinaldi M. Infections due to Cunninghamella bertholletiae in patients with cancer: report of three cases and review. Clin Infect Dis 1994;18(6):925–8; doi:10.1093/clinids/18.6.925
37. Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years. Arch Intern Med 1999;159(12):1301–9; doi:10.1001/archinte.159.12.1301
38. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in a tertiary-care cancer center. Clin Infect Dis 2000;30(6):851–6; doi:10.1086/313803
39. Rabin ER, Lundberg GD, Mitchell ET. Mucormycosis in severely burned patients. Report of two cases with extensive destruction of the face and nasal cavity. N Engl J Med 1961;264:1286–89; doi:10.1056/NEJM196106222642504
40. Paparello SF, Parry RL, MacGillivray DC, Brock N, Mayers DL. Hospital-acquired wound mucormycosis. Clin Infect Dis 1992;14(1):350–2; doi:10.1093/clinids/14.1.350
41. 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;41(5):634–53; doi:10.1086/432579
42. Lin E, Moua T, Limper AH. Pulmonary mucormycosis: clinical features and outcomes. Infection, 2017;45(4):443–8; doi:10.1007/s15010-017-0991-6
43. Kwon-Chung KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (Zygomycosis) and nomenclature of the disease: molecular mycologic perspectives. Clin Infect Dis. 2012;54(Suppl 1):S8–15; doi:10.1093/cid/cir864
44. Patra S, Vij M, Chirla DK, Kumar N, Samal SC. Unsuspected invasive neonatal gastrointestinal mucormycosis: a clinicopathological study of six cases from a tertiary care hospital. J Indian Assoc Pediatr Surg 2012;17(4):153–6; doi:10.4103/0971-9261.102329
45. Chakrabarti A, Singh R. Mucormycosis in India: unique features. Mycoses 2014;57(Suppl 3):85–90; doi:10.1111/myc.12243
46. Chander J, Stchigel AM, Alastruey-Izquierdo A et al. Fungal necrotizing fasciitis, an emerging infectious disease caused by Apophysomyces (Mucorales). Rev Iberoam Micol 2015;32(2):93–8; doi:10.1016/j.riam.2014.06.005
47. Sugar AM. Agents of mucormycosis and related species. In: Mandel GL, Bennett JE, Dolin R (eds.). Principles and practice of infectious diseases. 5th edition, Churchill Livingstone, Philadelphia, PA, vol 2, pp 2685–95, 2000.
48. Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diagnosis of mucormycosis: an update. J Fungi (Basel) 2020;6(4):265; doi:10.3390/jof6040265
49. Waldorf AR. Pulmonary défense mechanisms against opportunistic fungal pathogens. Immunol Ser 1989;47:243–71.
50. Morace G, Borghi E. Invasive mold Infections: virulence and pathogenesis of Mucorales. Int J Microbiol 2012;2012:349278; doi:10.1155/2012/349278
51. 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;56(1):29–43; doi:10.1093/mmy/myx017
52. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management [presentation]. Clin Microbiol Rev 2005;18(3):556–69; doi:10.12688/f1000research.15081.1
53. Pilmis B, Alanio A, Lortholary O, Lanternier F. Recent advances in the understanding and management of mucormycosis. F1000Res 2018;7:F1000.
54. Chakrabarti A, Das A, Sharma A, Panda N, Das S, Gupta KL, et al. Ten years’ experience in Zygomycosis at a tertiary care center in India. J Infect 2001;42(4):261–6; doi:10.1053/jinf.2001.0831
55. Chakrabarti A, Das A, Mandal J et al. The rising trend of invasive Zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol 2006;44(4):335–42; doi:10.1080/13693780500464930
56. 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;85(1009):573–81; doi:10.1136/pgmj.2008.076463
57. Manesh A, Rupali P, Sullivan MO, Mohanraj P, Rupa V, George B, et al. Mucormycosis-A clinicoepidemiological review of cases over 10 years. Mycoses, 2019;62(4):391–8; doi:10.1111/myc.12897
58. Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi (Basel) 2019;5(1):26; doi:10.3390/jof5010026
59. Patel A, Kaur H, Xess I, Michael JS, Savio J, Rudramurthy S, et al. A multi-centre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clin Microbiol Infect 2020;26(7):944.e9–15; doi:10.1016/j.cmi.2019.11.021
60. Chakrabarti A, Sood P, Denning D. Estimating fungal infection burden in India: mucormycosis burden as a case study [Internet]. 2021. Available via https://www.gaffi.org/wp-content/uploads/P1044.pdf
61. Chander J, Kaur M, Singla N, Punia RPS, Singhal SK, Attri AK, et al. Mucormycosis: battle with the deadly enemy over a five-year period in India. J Fungi (Basel), 2018;4(2):46; doi:10.3390/jof4020046
62. Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med 2021;42:264.e5–8; doi:10.1016/j.ajem.2020.09.032
63. Cocanour CS, Miller-Crotchett P, Reed 2nd RL, Johnson PC, Fischer RP. Mucormycosis in trauma patients. J Trauma 1992;32(1):12–5; doi:10.1097/00005373-199201000-00003
64. Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol 1994;39(1):3–22; doi:10.1016/s0039-6257(05)80041-4
65. Hamdi T, Karthikeyan V, Alangaden GJ. Mucormycosis in a renal transplant recipient: case report and comprehensive review of literature. Alangaden, Hindawi Publishing Corporation. Int J Nephrol 2014;2014:950643; doi:10.1155/2014/950643
66. Hernandez Jorge L, Buckley CJ. Mucormycosis. StatPearls, Treasure Island, FL, 2020.
67. Bell S, Mahoney L. Mucormycosis: a case study. Crit Care Nurse 2000;20(1):18–23; doi:10.4037/ccn2000.20.1.18
68. Chow V, Khan S, Balogun A, Mitchell D, Mühlschlegel FA. Invasive rhino-orbito-cerebral mucormycosis in a diabetic patient—the need for prompt treatment. Med Mycol Case Rep, 2015;8:5–9; doi:10.1016/j.mmcr.2014.12.002
69. Chowdhary A, Tarai B, Singh A, Sharma A. Multidrug-resistant Candida auris infections in critically Ill coronavirus disease patients, India, April–July 2020. Emerg Infect Dis 2020;26(11):2694–6; doi:10.3201/eid2611.203504
70. Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19, and orbital mucormycosis. Indian J Ophthalmol 2021;69(4):1002–4; doi:10.4103/ijo.IJO_3763_20
71. Sen M, Lahane S, Lahane TP, Parekh R, Honavar SG. Mucor in a viral land: a tale of two pathogens. Indian J Ophthalmol 2021;69(2):244–52; doi:10.4103/ijo.IJO_3774_20
72. John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis. J Fungi (Basel) 2021;7(4):298; doi:10.3390/jof7040298
73. Bassetti M, Bouza E. Invasive mold infections in the ICU setting: complexities and solutions. J Antimicrob Chemother 2017;72(suppl_1):i39–47; doi:10.1093/jac/dkx032
74. Reid G, Lynch JP, Fishbein MC, Clark NM. Mucormycosis. Semin Respir Crit Care Med 2020;41(1):99–114; doi:10.1055/s-0039-3401992
75. Kataria SP, Sharma J, Singh G, Kumar S, Malik S, Kumar V. Primary breast mucormycosis: FNAC diagnosis of a rare entity. Diagn Cytopathol 2016;44(9):761–3; doi:10.1002/dc.23510
76. Hadgaonkar S, Shah K, Bhojraj S, Nene A, Shyam A. Isolated mucormycotic spondylodiscitis of lumbar spine-A rare case report. J Orthop Case Rep 2015;5(2):55–7; doi:10.13107/jocr.2250-0685.275
77. Shah K, Nene A. Spinal mucormycosis. J Glob Infect Dis 2017;9(4):160–1. doi:10.4103/jgid.jgid_107_16
78. Bhatt M, Soneja M, Fazal F, Vyas S, Kumar P, Jorwal P, et al. Two cases of osteoarticular mucor menace: a diagnostic and management conundrum. Drug Discov Ther 2018;12(6):374–8; doi:10.5582/ddt.2018.01064
79. Urs AB, Singh H, Mohanty S, Sharma P. Fungal osteomyelitis of maxillofacial bones: rare presentation. J Oral Maxillofac Pathol 2016;20(3):546; doi:10.4103/0973-029X.190966
80. Forbes.com. What is behind the deadly rise in mucormycosis infections in India? Available via https://www.forbes.com/sites/judystone/2021/06/03/murder-mystery-what-is-behind-the-deadly-rise-in-mucormycosis-infections-in-india (Accessed 5 June 2021).
81. Timesofindia.indiatimes.com. Corona virus black fungus symptoms: when and how to check if mucormycosis has been triggered by COVID-19. Available via http://timesofindia.indiatimes.com/life-style/health-fitness/health-news/coronavirus-black-fungus-symptoms-when-and-how-to-check-if-mucormycosis-has-been-triggered-by-covid-19/photostory/83169411.cms?picid=83169634 (Accessed 2 June 2021).
82. Tribuneindia.com. Chandigarh: India witnessed two-fold increase in mucormycosis cases: CDC study Available from: http://tribuneindia.com/news/nation/india-witnessed-two-fold-increase-in-mucormycosis-cases-cdc-study-263891. (Accessed 6 June 2021).
83. Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Lancet Respir Med 2021;9(8):e77. https://doi.org/10.1016/ S2213-2600(21)00265-4
84. thehindu.com [Internet]. Chennai: India is home to 77 million diabetics, the second highest in the world [Updated 2019, November 15]. Available via https://www.thehindu.com/sci-tech/health/india-has-second-largest-number-of-people-with-diabetes/article29975027.ece
85. McNulty JS. Rhinocerebral mucormycosis: predisposing factors. Laryngoscope 1982;92(10 Pt 1):1140–3; doi:10.1288/00005537-198210000-00007
86. Kwon-Chung KJ, Bennett JE. Medical mycology. Rev Inst Med Trop S Paulo 1992;34(6):504; doi:10.1590/S0036-46651992000600018
87. Lanternier F, Dannaoui E, Morizot G, Elie C, Garcia-Hermoso D, Huerre M, et al. A global analysis of mucormycosis in France: the RetroZygo study. Clin Infect Dis, 2012;54(suppl 1):S35–43; doi:10.1093/cid/cir880
88. Ibrahim AS, Edwards JEJ, Filler SG. Zygomycosis241–251 in. In: Dismukes WE, Pappas PG, Sobel JD (eds.). Clinical mycology. Oxford University Press, New York, NY, 2003.
89. Farmakiotis D, Kontoyiannis DP. Mucormycosis. Infect Dis Clin North Am 2016;30(1):143–63; doi:10.1016/j.idc.2015.10.011
90. 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;82:105957.
91. Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD, Lowe JE. Pulmonary mucormycosis: results of medical and surgical therapy. Ann Thorac Surg 1994;57(4):1044–50; doi:10.1016/0003-4975(94)90243-7
92. Jacobs S, Gonzalez CE, Walsh TJ. Mucormycosis and Entomophthoramycosis. 2nd edition, 2002. Available via http://www.antimicrobe.org/f13.asp
93. Deepak G, Muthu V, Sehgal I, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus disease (Covid-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia 2021;186(2):289–98; doi:10.1007/s11046-021-00528-2.
94. Ghafur A, Shareek PS, Senthur NP, Vidyalakshmi PR, Ramasubramanian V, Parameswaran A, et al. Mucormycosis in patients without cancer: A case series from a tertiary care hospital in South India. J Assoc Physicians India 2013;61(5):305–8.
95. Bala K, Chander J, Handa U, Punia RS, Attri AK. A prospective study of mucormycosis in north India: experience from a tertiary care hospital. Med Mycol 2015;53(3):248–257. doi:10.1093/mmy/myu086
96. Vaezi A, Moazeni M, Rahimi MT et al. Mucormycosis in Iran: A systematic review. Mycoses 2016;59(7):402–15. doi:10.1111/myc.12474
97. Khor BS, Lee MH, Leu HS, Liu JW. Rhinocerebral mucormycosis in Taiwan. J Microbiol Immunol Infect 2003;36(4):266–9.
98. Nithyanandam S, Jacob MS, Battu RR, Thomas RK, Correa MA, D’Souza O. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol 2003;51(3):231–6.
99. O’Brien TJ, McKelvie P. Rhinocerebral mucormycosis presenting as periorbital cellulitis with blindness: report of 2 cases. Clin Exp Neurol 1994; 31:68–78.
100. Kasper D, Fauci A, Hauser S, Longo D, Jameson JL, Loscalzo J. Harrison’s principles of internal medicine. McGraw-Hill Education, New York, NY, p 19e, 1994.
101. Dhiwakar M, Thakar A, Bahadur S. Improving outcomes in rhinocerebral mucormycosis–early diagnostic pointers and prognostic factors. J Laryngol Otol 2003;117(11):861–5.
102. Peterson KL, Wang M, Canalis RF, Abemayor E. Rhinocerebral mucormycosis: evolution of the disease and treatment options. Laryngoscope 1997;107(7):855–62.
103. Thajeb P, Thajeb T, Dai D. Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy. Sc J Infect Dis 2004;36(9):643–8; doi:10.1080/00365540410020794
104. Stoeckle M, Kaech C, Trampuz A, Zimmerli W. The role of diabetes mellitus in patients with bloodstream infections. Swiss Med Wkly 2008;138(35–36):512–9.
105. Flyvbjerg A. Diabetic angiopathy, the complement system, and the tumor necrosis factor superfamily. Nat Rev Endocrinol 2010;6(2):94–101; doi:10.1038/nrendo.2009.266
106. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol 1999;26(3–4):259–65; doi:10.1111/j.1574-695X.1999.tb01397.x
107. Peleg AY, Weerarathna T, McCarthy JS, Davis TM. Common infections in diabetes: pathogenesis, management, and relationship to glycaemic control. Diabetes Metab Res Rev 2007;23(1):3–13; doi:10.1002/dmrr.682
108. Sheldon WH, Bauer H. The development of the acute inflammatory response to experimental cutaneous mucormycosis in normal and diabetic rabbits. J Exp Med 1959;110:845–52; doi:10.1084/jem.110.6.845
109. Waldorf AR, Ruderman N, Diamond RD. Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J Clin Invest 1984;74(1):150–60; doi:10.1172/JCI111395
110. Khan M, Adil SF, Alkhathlan HZ, Tahir MN, Saif S, Khan M, et al. COVID-19: a global challenge with old history, epidemiology, and progress so far. Molecules 2020;26(1):39; doi:10.3390/molecules26010039
111. Mehta S, Pandey A. Rhino?orbital mucormycosis associated with COVID?19. Cureus 2020;12(9):e10726; doi:10.7759/cureus.10726
112. Monte Junior ESD, Santos MELD, Ribeiro IB, Luz GDO, Baba ER, Hirsch BS, et al. Rare and fatal gastrointestinal mucormycosis (Zygomycosis) in a COVID-19 patient: a case report. Clin Endosc 2020;53(6):746–9; doi:10.5946/ce.2020.180
113. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet 2011;377(9773):1264–75; doi:10.1016/S0140-6736(10)61459-6
114. Medpagetoday.com. Superinfections and coinfections in COVID-19. Available via http://medpagetoday.com/infectiousdisease/covid19/86192 (Accessed 28 April 2020)
115. Segrelles-Calvo G, Glauber Rde S (1405–1413) ISSN 1746-0913. Araujo´ 2,3 and Susana Frases, Systemic mycoses: a potential alert for complications in COVID-19 patients Serviciode Neumologia. [Hospital Universitario Rey Juan Carlos, Instituto de Investigacion Biomedica Fundaci] on Jim’ e10.2217/fmb-2020-0156]. Future Microbiol 2020;15(14):C2020.
116. Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, et al. Mucormycosis ECMM MSG global guideline writing group. Lancet Infect Dis 2019;19(12):e405–21; doi:10.1016/S1473-3099(19)30312-3
117. Saha O, Rakhi NN, Sultana A, Rahman MM, Rahaman MM. SARS-CoV-2 and COVID-19: a threat to global health. Discov Rep 2020;3:e13; doi:10.15190/drep.2020.7
118. Gangneux JP, Bougnoux ME, Dannaoui E, Cornet M, Zahar JR. Invasive fungal diseases during COVID-19: we should be prepared. J Mycol Med, 2020;30(2):100971; doi:10.1016/j.mycmed.2020.100971
119. 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; doi:10.1016/S2213-2600(20)30079-5.
120. 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.
121. Pemán J, Ruiz-Gaitán A, García-Vidal C, Salavert M, Ramírez P, Puchades F, et al. Fungal co-infection in COVID-19 patients: should we be concerned? Rev Iberoam Micol 2020;37(2):41–6; doi:10.1016/j.riam.2020.07.001
122. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5
123. Tan M, Liu Y, Zhou R, Deng X, Li F, Liang K, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. Immunology 2020;160(3):261–8; doi:10.1101/2020.03.12.20034736
124. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al (2020) Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis 2020;71(15):762–8; doi:10.1093/cid/ciaa248
125. Zhang B, Zhou X, Zhu C, Feng F, Song Y, Feng F, Qiu Y, et al. Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19. Front Mol Biosci 2020;7:157; doi:10.1101/2020.03.12.20035048
126. Peng M, Meng H, Sun Y, Xiao Y, Zhang H, Lv K, et al. Clinical features of pulmonary mucormycosis in patients with different immune status. J Thorac Dis, 2019;11(12):5042–52; doi:10.21037/jtd.2019.12.53.
127. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020;395(10229):1054–62; doi:10.1016/S0140-6736(20)30566-3.
128. Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020;323(18):1775–6; doi:10.1001/jama.2020.4683
129. Kothandaraman N, Rengaraj A, Xue B, Yew WS, Velan SS, Karnani N, et al. COVID-19 endocrinopathy with hindsight from SARS. Am J Physiol Endocrinol Metab, 2021;320(1):E139–50; doi:10.1152/ajpendo.00480.2020
130. 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;68(4):213–24; doi:10.1007/s12026-020-09145-5
131. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012;54(suppl 1):S16–22; doi:10.1093/cid/cir865
132. Punjabnewsexpress.com. Diabetes is a major risk factor in mucormycosis case. Available via https://www.punjabnewsexpress.com/health/news/diabetes-is-a-major-risk-factor-in-mucormycosis-cases-balbir-sidhu-138849 (Accessed 2 June 2021)
133. Wionews.com. Black fungus infections on rise in India: Antifungal drug: mucormycosis. Available via https://www.youtube.com/watch?v=2ykmpigRp-c (Accessed 20 May 2021).
134. Almyroudis NG, Sutton DA, Linden P, Rinaldi MG, Fung J, Kusne S. Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature. Am J Transplant 2006;6(10):2365–74; doi:10.1111/j.1600-6143.2006.01496.x
135. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L. et al. Dexamethasone in hospitalized patients with COVID-19—preliminary report. N Engl J Med 2021;384(8):693–704; doi:10.1056/NEJMoa2021436
136. Pal R, Banerjee M. COVID-19, and the endocrine system: exploring the unexplored. J Endocrinol Invest 2020;3:9.
137. Wood BR, Lacy JM, Johnston C, Weigle DS, Dhanireddy S. Adrenal insufficiency as a result of ritonavir and exogenous steroid exposure: report of 6 cases and recommendation for management. J Int Assoc Provide Aids Care 2015;14:300–5; doi:10.1177/2325957414
138. Ferraù F, Ceccato F, Cannavò S, Scaroni C. What we have to know about corticosteroids use during SARS-CoV-2 infection. J Endocrinol Invest 2021;44(4):693–701; doi:10.1007/s40618-020-01384-5
139. Berton AM, Prencipe N, Giordano R, Ghigo E, Grottoli S. Systemic steroids in patients with COVID?19: pros and contras, an endocrinological point of view. J Endocrinol Invest 2021;44(4):873–75; doi:10.1007/s40618-020-01325-2
140. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with corona virus Disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180(7):934–43; doi:10.1001/jamainternmed.2020.0994
141. Gemelli Against COVID-19 Post-Acute Care Study Group. Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res 2020;32(8):1613–20; doi:10.1007/s40520-020-01616-x
142. Timesofindia.indiatimes.com. Mumbai: zinc overuse driving black fungus epidemic within pandemic? Doctors want study. Available via https://timesofindia.indiatimes.com/city/mumbai/mumbai-zinc-overuse-driving-mucor-epidemic-within-pandemic-docs-want-study/articleshow/82922957.cm (Accessed 25 May 2021).
143. News18.com. Amid mucormycosis outbreak, doctors seek research on role of zinc supplement. Available via https://www.news18.com/news/india/mucormycosis-black-fungus-zinc-supplements-covid-19-coronavirus-3781526.html (Accessed 27 May 2021).
144. Cnbctv18.com. Doctors suspects overuse of zinc and iron increases risk of black fungus infections. Available via https://www.cnbctv18.com/healthcare/doctors-suspect-overuse-of-zinc-and-iron-increases-risk-of-black-fungus-infection-9440491.htm (Accessed 26 May 2021).
145. Chougule A, Muthu V, Bal A, Rudramurthy SM, Dhooria S, et al. Pulmonary gangrene due to Rhizopus spp Staphylococcus aureus Klebsiella pneumoniae and probable Sarcina organisms. Mycopathologia 2015;180(1–2):131–6; doi:10.1007/s11046-015-9904-3
146. Muthu V, Dhooria S, Singh Sehgal I, Thurai Prasad K, Agarwal R. The reversed halo sign and the bronchus sign: the eyes see only what the mind knows. Ann Am Thorac Soc 2019;16(9):1203; doi:10.1513/AnnalsATS.201905-360LE.
147. Pandey N, Vipin K, Dutt P, Taneja S, Biswal M, Mahajan P, et al. Transforming a general hospital to an infectious disease hospital for COVID for COVID-19 over 2 weeks. Front Public Health 2020;8:382; doi:10.3389/fpubh.2020.00382
148. Economictimes.indiatimes.com. Covid infection, diabetes and misuse of steroids during treatment responsible for increase in mucormycosis cases: Randeep Gluleria, AIIMS Director. Available via https://economictimes.indiatimes.com/news/india/covid-infection-diabetes-and-misuse-of-steroids-during-treatment-responsible-for-increase-in-mucormycosis-cases-randeep-guleria-aiims-director/videoshow/82658230.cms (Accessed 15 May 2021).
149. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497–506; doi:10.1016/S0140-6736(20)30183-5
150. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev 2020;7(6):998–1002; doi:10.1093/nsr/nwaa041
151. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 2020;15(5):700–4; doi:10.1016/j.jtho.2020.02.010
152. Chen J, Wang R, Wang M, Wei GW. Mutations strengthened SARS-CoV-2 infectivity. J Mol Biol 2020;432(19):5212–26; doi:10.1016/j.jmb.2020.07.009
153. Icmr.gov.in. Evidence based advisory in the time of COVID-19 (Screening, diagnosis, and management of mucormycosis). Available via https://www.icmr.gov.in/pdf/covid/techdoc/Mucormycosis_ADVISORY_FROM_ICMR_In_COVID19_time.pdf
154. Indiatoday.com. New Delhi: Covid-19 patients on home care should not take remdesivir: AIIMS. Available via doctorshttps://www.indiatoday.in/coronavirus-outbreak/story/covid-19-patients-on-home-care-should-not-take-remdesivir-aiims-doctors-1802999-2021-05-15 [Accessed 15 May 2021).
155. Indiatoday.in. New Delhi: DGHS drops Ivermectin, Doxycycline from Covid-19 treatment; ICMR rules unchanged. Available via https://www.indiatoday.in/coronavirus-outbreak/story/revised-health-ministry-guidelines-stop-usage-of-ivermectin-doxycycline-in-covid-treatment-1811809-2021-06-07. (Accessed 7 June 2021).
156. Firstpost.com. DGHS issue COVID-19 treatment guidelines: here is what document recommends on Remdesivir, Tocilizumab. Available via https://www.firstpost.com/health/dghs-issues-covid-19-treatment-guidelines-here-is-what-document-recommends-on-remdesivir-tocilizumab-9695581.html (Accessed 8 June 2021).
157. Livemint.com. Drugs including ivermectin removed from approved covid treatment list. Available via https://www.livemint.com/news/india/govt-removes-ivermectin-other-popular-drugs-from-covid-19-treatment-list-check-revised-guidelines-11623074154396.html (Accessed 9 June 2021).