|Year : 2022 | Volume
| Issue : 4 | Page : 462-465
Mucormycosis: An addendum to India's COVID-19 woes
Department of Anthropology, University of North Bengal, Darjeeling, West Bengal, India
|Date of Submission||03-Aug-2021|
|Date of Decision||05-Sep-2021|
|Date of Acceptance||18-Sep-2021|
|Date of Web Publication||01-Feb-2022|
Department of Anthropology, University of North Bengal, Darjeeling, West Bengal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Roy S. Mucormycosis: An addendum to India's COVID-19 woes. Med J DY Patil Vidyapeeth 2022;15:462-5
| Introduction|| |
COVID-19 is the acronym for the full term “coronavirus disease of 2019.” The disease was reported to have originated in Wuhan, China in the late 2019s and has now become a serious pandemic worldwide. COVID-19 brings about several known and unknown symptoms of which fever or chill, cough, shortness of breath or difficulty in breathing, sore throat, runny nose, loss of sense of taste or smell, fatigue, and muscle ache are considered as cardinal symptoms. In some cases, diarrhea, conjunctivitis, nausea and/or vomiting, skin rashes, discoloration of fingers, and toes may also accompany. Although there is a long catalog of possible symptoms of COVID-19, infected persons often face several other post-COVID health disorders. One such fatal health disorder reported in India is “mucormycosis.”
| Mucormycosis and Its Potential Factors|| |
Mucormycosis (previously called zygomycosis; colloquially known as “black fungus”) is a serious invasive fungal infection caused by a group of related molds belonging to the Mucormycotina subphylum, Mucorales order and the Mucoraceae family. The fungi are pervasive throughout the environment and thrive mainly in the soil, plants, manure, and decaying fruits and vegetables. Although “mucormycosis” was previously considered as a very rare infection, the prevalence of mucormycosis in India was recently reported to be approximately 0.14 cases per 1000 population, which is equivalent to about 80 times the prevalence of mucormycosis in developed countries. With the surge of COVID-19 cases, doctors in India are observed to report a rise of mucormycosis infections among the recovering and recovered COVID-19 patients. For now, it could be assumed that there exist several potential risk factors for contracting this serious fungal infection, such as:
Patients who had been treated with steroids:
It is assumed that the probable cause of mucormycosis to occur in (recovering and recovered) COVID-19 patients is indiscriminate use of steroids in the COVID-19 treatment. As has been made aware to us, COVID-19 is a serious respiratory disease where the SARS CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) invades and generates damaging effects on the lungs of the infected persons. Medications such as corticosteroids are then employed to alleviate lung inflammation caused by SARS CoV-2. Despite being a life-saving treatment for severe and critically ill COVID-19 patients, steroids bear several downside risks, such as they enhance the blood sugar levels in both diabetic and nondiabetic patients. Secondly, prolonged use of steroids can weaken the immune system. As it is a known fact, all medicines have its own pros and cons, so judicious evidence-based use of steroids and/or other medicines in COVID-19 patients is highly recommended. A very recent study has inferred that well-thought out clinical trials are imperative to evaluate the safety and efficacy of steroid therapy in COVID-19 treatment. Doctors must avoid irrational prescribing steroids for mild COVID-19 cases. They must avoid three main pitfalls while prescribing steroids: (i) their use too early (if oxygen levels have not dropped); (ii) their use routinely in higher doses than recommended (6 mg Dexamethasone a day, or 32 mg Methylprednisolone a day, or 40 mg Prednisolone a day, or 160 mg Hydrocortisone a day); (iii) their use for longer periods than recommended (up to 10 days).,
Patients with uncontrolled diabetes mellitus:
High blood sugar patients are prone to get infected from mucormycosis. Treatment of COVID-19 with steroids (discussed above) can yield a spike in blood sugar levels which can become more fatal for patients with uncontrolled diabetes. Diabetes often involves acid-base and electrolyte disorders which often results in metabolic acidosis. This is support by the fact that this fungal infection is mostly seen in diabetic patients having ketoacidosis. Henceforth, it could be conjectured that higher blood sugar and acidic blood serves as a prolific environment for the Mucorales fungi to thrive. In addition, diabetes has a tendency to weaken our immune system which can also pose a serious risk of contracting fungal infection. Clinicians must aim to focus on keeping blood sugar levels under control irrespective of the diabetic status COVID-19 patients.
Patients possessing weak immune system:
White blood cells (such as neutrophils, lymphocytes, eosinophils, basophils and monocytes) are an integral part of the immune system that defends our body against several infections and several other foreign invaders. Regrettably, there exists a strong association of severe COVID-19 cases and lower count of lymphocytes and neutrophils in the infected patients., On top of that, medications used in the treatment of COVID-19 (such as steroids) often bring down the number of lymphocytes. The reduced count of lymphocytes leads to a medical condition called lymphopenia, making way for opportunistic fungal infection in COVID-19 patients. This also possesses a serious threat of contracting the fungal infection in case of co-morbid and immuno-compromised patients (e.g., hematopoietic stem cell transplantation, or solid-organ transplant, malignancy, HIV/AIDS, etc.).,,,,
Patients with prolonged stay in intensive care unit (ICU) for COVID-19 treatment:
Patients undergoing oxygen therapy in ICU get exposed to moisture from humidifier which makes them more prone to the infection from mucormycosis. In certain cases, ordinary tap water used in the flow meter of the oxygen cylinders is also inculpated. Risks can also be triggered from “mould-tainted oxygen piper and humidifier.” Previously, mounting evidences have claimed contaminated hospital linens as a possible source for mucormycosis outbreak.,, A very recent review claimed that outbreak of fungal infections (including mucormycosis) could be from several sources from hospitals such as:
- Through non-sterile products (such as bandages, patches, tape, and adhesives; contaminated laundered textiles; wooden tongue depressors; medications, supplements and food)
- Through several procedures (e.g. dental procedures), devices (such as catheters and tubes, insulin pumps, and finger sticks) and transplant surgery
- Through several environmental sources such as insufficient air filtration, negative pressure rooms, water leaks, etc.
Patients who had undergone voriconazole therapy:
Voriconazole therapy is a sort of anti-fungal therapy used to treat several fungal infections such as aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, etc., However, it lacks activity against the Mucorales.,, Several previous studies had claimed voriconazole pre-exposure as a serious risk factor for mucormycosis.,,,,
| Symptoms Associated with Mucormycosis|| |
Like COVID-19, the symptoms of mucormycosis and progression of the infection are found to differ from person to person. The symptoms of mucormycosis vary widely depending on the location of the infection: Rhinocerebral (sinuses and brain), pulmonary (lungs), cutaneous (skin), and gastrointestinal mucormycosis. Another type of mucormycosis called disseminated mucormycosis is reported especially among immunocompromised patients. However, majority of the cases of “COVID-19 associated mucormycosis” occur in the extreme form of rhinocerebral mucormycosis. Due to rich blood supply, the main organs such as eyes, nose, brain, lungs, and the sinuses are mostly reported to get affected. The pathophysiology of the fungal infection involves inhalation of fungal spores through the respiratory tract (nose or mouth) or even through a skin trauma (such as cuts, scrape, and burns). It then spreads through the paranasal sinuses and consequently to the orbit, meninges, and brain finally generating symptoms such as throbbing headache, fever, sinusitis, facial and nasal pain, blackish nasal discharge, blurred or double vision (loss of vision in severe cases), toothache, loosening of teeth, swelling in the upper jaw, and sometimes face paralysis. Pulmonary mucormycosis involving chest pain, pleural affusion, hemoptysis, and worsening of respiratory symptoms are also reported to occur in certain cases., In severe cases, when the early symptoms are ignored and not treated, the fungal infection may spread from one organ to another through blood vessels. Invasion into the blood vessels can result in thrombosis and sometimes necrosis (due to loss of blood supply). In extreme case, death may also occur.
| Prevention|| |
Unfortunately, the prognosis of mucormycosis is worse because of its high invasive power and its intrinsic low susceptibility to antifungal agents. Although mucormycosis is not contagious, prompt diagnosis and early treatment are highly demanding. Diagnostic methods usually involve biopsy and culture study. To find the extent of the infection, medical imaging is often employed. Treatment usually involves anti-fungal medications (such as Amphotericin B). In severe cases, surgical intervention is recommended to remove the affected tissue. The latter is recommended to prevent the spread of mucormycosis to other parts of the body and also to prevent mortality rate associated with this fatal disease.
At present, “COVID-19-associated mucormycosis” has now become a serious pandemic in India. We all must take serious steps to protect ourselves from such calamities. Steps such as monitoring blood sugar levels regularly, prescribing nil or limited steroids in case of mild COVID-19 cases, using antibiotics and anti-fungal medications judiciously, wearing (double) masks to prevent the entry of spores through nose, improving personal and oral hygiene, reporting the early warning signs and symptoms of mucormycosis, maintaining proper hygiene and sanitization in the hospitals, using sterile and clear water for humidifiers during oxygen therapy, etc., Moreover, an early diagnosis of “COVID-19-associated mucormycosis” in addition to medical and surgical intervention is also required to improve the outcome.
| References|| |
Chander J, Singla N, Kaur M, Punia RS, Attri A, Alastruey-Izquierdo A, et al
. Saksenaea erythrospora
, an emerging mucoralean fungus causing severe necrotizing skin and soft tissue infections – A study from a tertiary care hospital in north India. Infect Dis 2017;49:170-7.
Mattos-Silva P, Felix NS, Silva PL, Robba C, Battaglini D, Pelosi P, et al.
Pros and cons of corticosteroid therapy for COVID-19 patients. Respir Physiol Neurobiol 2020;280:103492.
Sotirakopoulos N, Kalogiannidou I, Tersi M, Armentzioiou K, Sivridis D, Mavromatidis K. Acid-base and electrolyte disorders in patients with diabetes mellitus. Saudi J Kidney Dis Transpl 2012;23:58-62.
] [Full text]
Afroze SN, Korlepara R, Rao GV, Madala J. Mucormycosis in a diabetic patient: A case report with an insight into its pathophysiology. Contemp Clin Dent 2017;8:662-6.
] [Full text]
Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev 2020;16:442-9.
Huang I, Pranata R. Lymphopenia in severe coronavirus disease-2019 (COVID-19): Systematic review and meta-analysis. J Intensive Care 2020;8:36.
Devi YM, Sehrawat A, Panda PK, Nath UK. Febrile neutropenia due to COVID-19 in an immunocompetent patient. BMJ Case Rep 2021;14:e242683.
Yan S, Wu G. Is lymphopenia different between SARS and COVID-19 patients? FASEB J 2021;35:e21245.
Xhaard A, Lanternier F, Porcher R, Dannaoui E, Bergeron A, Clement L, et al.
Mucormycosis after allogeneic haematopoietic stem cell transplantation: A French Multicentre Cohort Study (2003-2008). Clin Microbiol Infect 2012;18:E396-400.
Yasmeen S, Waqas O, Munir J, Sultan F, Hameed A. Hepatosplenic mucormycosis post autologous stem cell transplant. Pak J Med Sci 2017;33:776-8.
Moreira J, Varon A, Galhardo MC, Santos F, Lyra M, Castro R, et al.
The burden of mucormycosis in HIV-infected patients: A systematic review. J Infect 2016;73:181-8.
Madney Y, Khedr R, Al-Mahellawy H, Adel N, Taha H, Zaki I, et al.
“Mucormycosis” the emerging global threat; overview and treatment outcome among pediatric cancer patients in Egypt. Blood 2017;130 Supp 1:4830.
Song Y, Qiao J, Giovanni G, Liu G, Yang H, Wu J, et al.
Mucormycosis in renal transplant recipients: Review of 174 reported cases. BMC Infect Dis 2017;17:283.
Duffy J, Harris J, Gade L, Sehulster L, Newhouse E, O'Connell H, et al.
Mucormycosis outbreak associated with hospital linens. Pediatr Infect Dis J 2014;33:472-6.
Cheng VC, Chen JH, Wong SC, Leung SS, So SY, Lung DC, et al.
Hospital outbreak of pulmonary and cutaneous zygomycosis due to contaminated linen items from substandard laundry. Clin Infect Dis 2016;62:714-21.
Sundermann AJ, Clancy CJ, Pasculle AW, Liu G, Cumbie RB, Driscoll E, et al.
How clean is the linen at my hospital? The Mucorales
on unclean linen discovery study of large United States transplant and cancer centers. Clin Infect Dis 2019;68:850-3.
Hartnett KP, Jackson BR, Perkins KM, Glowicz J, Kerins JL, Black SR, et al
. A guide to investigating suspected outbreaks of mucormycosis in healthcare. J Fungi (Basel) 2019;5:69.
Siwek GT, Pfaller MA, Polgreen PM, Cobb S, Hoth P, Magalheas-Silverman M, et al.
Incidence of invasive aspergillosis among allogeneic hematopoietic stem cell transplant patients receiving voriconazole prophylaxis. Diagn Microbiol Infect Dis 2006;55:209-12.
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al.
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.
Almyroudis NG, Sutton DA, Fothergill AW, Rinaldi MG, Kusne S. In vitro
susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother 2007;51:2587-90.
Marty FM, Cosimi LA, Baden LR. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 2004;350:950-2.
Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, et al.
Zygomycosis in a tertiary-care cancer center in the era of Aspergillus
-active antifungal therapy: A case-control observational study of 27 recent cases. J Infect Dis 2005;191:1350-60.
Siwek GT, Dodgson KJ, de Magalhaes-Silverman M, Bartelt LA, Kilborn SB, Hoth PL, et al.
Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis 2004;39:584-7.
Gupta N, Kumar A, Singh G, Ratnakar G, Vinod KS, Wig N. Breakthrough mucormycosis after voriconazole use in a case of invasive fungal rhinosinusitis due to Curvularia lunata
. Drug Discov Ther 2017;11:349-52.
Chakrabarti A, Kaur H, Savio J, Rudramurthy SM, Patel A, Shastri P, et al.
Epidemiology and clinical outcomes of invasive mould infections in Indian Intensive Care Units (FISF study). J Crit Care 2019;51:64-70.
Spellberg B, Edwards J Jr., Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.
Claustre J, Larcher R, Jouve T, Truche AS, Nseir S, Cadiet J, et al.
Mucormycosis in intensive care unit: Surgery is a major prognostic factor in patients with hematological malignancy. Ann Intensive Care 2020;10:74.
Grossman ME, Fox LP, Kovarik C, Rosenbach M. Cutaneous Manifestations of Infection in the Immunocompromised Host. 2nd
ed. New York: Springer; 2012.