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Opportunistic Fungal Infections Post-COVID: How Threatened Are We?
Quite unlike the previous wave, we are witnessing the harrowing emergence of a deadly and serious morbidity-inflicting condition diagnosed as mucormycosis in the current upsurge of coronavirus disease 2019 (COVID-19) due to Delta variant (B.1.617.2 strain) of severe acute respiratory syndrome coronavirus 2. Mucormycosis is an opportunistic fungal infection caused by (SARS-COV-2) fungi belonging to the order Mucorales, and specifically Rhizopus oryzae species are by far the most common cause of infection.
Mucormycosis, colloquially, known as black fungus is a serious infection that was seen in very rare numbers in India before COVID-19, but it is now affecting post-COVID patients in large numbers. This fungus is present everywhere on soil, bread mould, rotten fruit and vegetables and humans have a strong natural resistance to the infection. This organism is frequently found to colonise the oral mucosa, nasal mucosa, paranasal sinuses and pharyngeal mucosa of asymptomatic patients. These fungi do not usually cause disease in healthy people with intact immune systems, but patients with certain health conditions can be predisposed to the development of invasive fungal disease.  The spores of the fungus enter the body mostly by inhalation during COVID-19 infection or after a few weeks of apparent recovery from it in whom immunity is critically low and can involve nose and sinuses, palate, maxilla, jawbone, lungs, eyes and brain. Commonest sites involved with mucormycosis are nose and sinuses, followed by rhino-orbital, and rhino-orbito-cerebral (ROCM). The hallmarks of disease caused by these pathogens are angioinvasion, thrombosis, ischemia and necrosis of involved tissue. Pathogenesis and mechanism of bone destruction are attributed to the reduced vascularity by thrombi formation.
Mucormycosis becomes pathogenic when the patient's general resistance has been altered by metabolic disorders, immunosuppressive therapy, malignancy or other chronic debilitating disorders.   An underlying disease, frequently diabetes mellitus, is almost always present. The major risk factors for mucormycosis are diabetic ketoacidosis (DKA), other forms of metabolic acidosis and immunocompromised patients.
For the current violent upsurge of this fungal infection, multiple hypotheses have been suggested such as the widespread and injudicious use of corticosteroids in terms of correct timing, dose and duration and cocktails of other drugs to patients with even mild COVID-19, excessive use of zinc supposedly to enhance immunity, mask hygiene, use of industrial oxygen which, although, have not yet been asserted. Experts now opine that the ‘Poly-Pharmacy’ phenomenon was irrational.
It is a proven fact that iron plays an important role in the growth of black fungus inside the body. This fungus has selective propensity to acquire iron from the host by using multiple processes. Recent data demonstrate that the level of available unbound iron in serum plays a critical factor in uniquely predisposing patients with DKA to mucormycosis.  DKA patients have high levels of serum iron and the blood pH ranging from 7.3 to 6.88 which is an ideal environment for growth of Rhizopus. It is also being viewed that due to it's inherent property of causing severe immune suppression and acute hyperglycemic state, delta variant renders COVID-19 patients vulnerable to opportunistic infections like mucormycosis unlike the original strain of the virus.
Diagnosing mucormycosis by imaging studies, serological tests and culture studies is not unswerving. Definitive diagnosis of mucormycosis is based on histopathological examination. Good clinical examination with history and astute clinical approach in commencing treatment without delay can reduce morbidity and mortality.
Rapidity of dissemination of mucormycosis is an extraordinary phenomenon. A delay of even 12 hours in instituting antifungal treatment could be lethal. The physician needs to vigilantly observe the prodromal symptoms without waiting for the pathological diagnosis and tissue changes to occur. Do not miss warning signs and symptoms like headache, fever, pain in cheek bones, nasal obstruction, blackish or bloody discharge from nose, pain, numbness and swelling, discoloration of skin of face, localised facial puffiness, blurred vision, drooping eyelids, double vision, redness or swelling around eye and nose, toothache/loosening of teeth, discoloration or ulceration of palate in a COVID-19 patient or during the first few weeks after recovery.
Since mucormycosis occurs infrequently, it may pose a diagnostic and therapeutic dilemma for those not familiar with its clinical presentation. Early diagnosis and management will lessen the chance of its spread to adjacent tissue and may have great advantages. The aim of writing this editorial is to alert the clinicians to be aware of mucormycosis on the importance of early diagnosis and management.
Role of homoeopathy on patients of mucormycosis has not been explored by undertaking specific studies on this highly fatal and morbidity-inflicting fungus. However, research studies conducted on various fungi in invitro model have shown that homoeopathic medicines could prevent their growth. Clinical studies have shown encouraging results on the role of homoeopathy in fungal infections in general. Ministry of AYUSH, Govt. of India, has brought out a list suggesting around 25 homoeopathic medicines for suspected and diagnosed patients having ROCM, pulmonary, cutaneous and gastrointestinal mucormycosis on the recommendation of selected panel of homoeopathic doctors.
In the absence of definitive scientific evidence, as an adjuvant to mainstream antifungal intervention, homoeopathy is worth giving a try.
Do not miss warning signs and symptoms of prodromal stage.
Do not consider all cases with blocked nose or sinusitis like symptoms to be bacterial sinusitis especially while dealing with COVID-19 patients.
Do not lose crucial time by hesitating to initiate aggressive antifungal intervention. Because of unacceptably high mortality rate and the extreme morbidity, emergent, extensive disfiguring surgical debridement to remove all necrotic tissue where the saprophyte is thriving in abundance is needed.
02 July 2021 (online)
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