While on one side, we continue to fight against COVID-19, on the other side, the issue of post-COVID-19 infections such as mucormycosis, has risen as a serious threat. India now holds the notorious reputation of being the world's centre for both diabetes and mucormycosis. This article throws light on understanding the condition and possible treatments keeping in mind the comorbidities. 

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COVID-19 versus diabetes

Diabetes is India's leading disease, with an estimated 77 million adult cases. According to a recent cross-sectional survey conducted across all Indian states, 47 per cent of Indians are ignorant of their diabetic status, and about a quarter of all diabetic patients maintain sufficient glycaemic regulation when on care.

Post COVID-19 sepsis is what happens when SARS-CoV-2 has wreaked havoc on the human body, leaving us to deal with the aftermath. It results in an abnormal innate immune response, ciliary malfunction, cytokine storm, thrombo-inflammation, microvascular coagulation, and ultimately immune fatigue. This sequence of events favours secondary bacterial and fungal infections, especially in sick patients undergoing emergency invasive surgeries, mechanical ventilation, CRRT, ECMO, low nurse-to-patient ratios, extended hospital stays, and asepsis violations. Additionally, the use of corticosteroids and anti-IL-6 therapies in these particularly vulnerable hosts, along with elevated fungal spore counts in the soil, provides new opportunities for mould infections.

Though COVID-19-associated pulmonary aspergillosis (CAPA) has gotten a lot of attention around the world, the Indian epidemiology of invasive mould infections in ICUs shows a large burden of invasive mucormycosis. In our world, this has recently arisen as a life-threatening COVID-19 complication. While the predisposing factors and pathogenesis are identical to those of other mould pathogens, certain distinct features and main distinguishing factors must be kept in mind in order to quickly suspect the infection, validate the diagnosis, and provide appropriate therapeutic action.

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What are mucorales?

Mucorales are common moulds that thrive on rotting organic matter in the atmosphere. Due to the primarily hot, humid weather in our tropical atmosphere, multiple studies from hospitals around the country have shown high mould spore counts also in hospital air. In contrast to CAPA, invasive mucormycosis has been reported in patients with mild to moderate SARS-CoV-2 infections. In undiagnosed or poorly regulated diabetics, the main predisposing factor tends to be hyperglycaemia. Polymorphonuclear dysfunction compromised chemotaxis, and faulty intracellular killing are all consequences of hyperglycaemia. Mucorales' ability to obtain iron from the host, which is required for its development, is a significant virulence feature.

Free iron becomes easily accessible in the serum in ketoacidosis. The mucorales efficiently absorb this surplus endogenous iron through siderophores or iron permeases, boosting their virulence even further. The use of corticosteroids and immunosuppressive drugs in vulnerable hosts amplifies the impact significantly. Neutrophil proliferation, ingestion, and phagolysosome fusion are all affected by corticosteroids. When combined with the possible consequences of steroid-induced hyperglycaemia, the diabetic COVID-19 patient taking corticosteroids or other immunosuppressive drugs is particularly vulnerable to the occurrence of mucormycosis.

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Impact of steroids

The groundbreaking RECOVERY trial, which was released in June 2020, established an 'authorisation' for the use of steroids in patients with COVID-19. But nevertheless, the facts and evidence made it abundantly clear that there were some critical messages which appear to have been missed. In moderate to serious disease, the benefit was directly demonstrated with a low dose, limited period dexamethasone. While higher doses and longer durations can be used for persuasive purposes in rare situations, those patients should be tested for undiagnosed diabetes, reviewed for stringent glycaemic regulation, and closely watched for secondary infections. A careless approach towards the use of steroids should be avoided at all times.

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Manifestations of mucormycosis

Mucormycosis has two major manifestations in this setting: rhino-orbital-cerebral and pulmonary. The presumption is focused on indirect clinical and imaging clues, risk factors, and disease initiation or worsening when taking some antibacterial or antifungal medication that doesn't mask mucor. To recognise mucor's confirmation, clinicians should have seen a "significant" number of incidents.

Tissue necrosis manifested as a necrotic lesion, eschar, or black discharge in the nasal or oral cavity, is the clinical characteristic. Involvement of the orbital, ocular, and cranial nerves are also warning signals that must be taken seriously. Alternative erroneous diagnoses result from the utilisation of antibacterials and further steroid therapy, which adds to the flames.

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Investigations

Biopsy, KOH mount, and calcofluor stain are also effective screening techniques. Mucor is notoriously difficult to culture regularly. Biopsy is the gold standard for diagnosis, and the benefits outweigh the risks, even in locations that are hard to reach or in the case of coagulopathy.

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Therapies 

Antifungal agents, surgical debridement, reversal of systemic predisposing causes, and adjunctive are all treatment standards. Amphotericin B has long been considered the gold standard for treating invasive mucormycosis. Patients treated with COVID-19 can cause acute or chronic renal impairment, which can be alleviated by transitioning to a less- or non-nephrotoxic substitute. As a result, Posaconazole or Isavuconazole may be needed. The above also has the benefit of shortening the QT interval, which may have been prolonged by HCQ, azithromycin, which many patients are also receiving.

Surgical debridement, performed as soon as possible, is critical in the treatment of mucormycosis. The best time for surgery to minimise the risk of infection in the patient with COVID-19 and spread to the operating team is a point of contention. After ten days, no virus capable of replication was recovered from patients with mild to moderate illness; after fifteen days, no virus capable of replication was recovered from any seriously ill patient.

Caspofungin, deferasirox, statins, aspirin, and hyperbaric oxygen can be used as adjuvant treatment. Mucormycosis must be actively treated by a multidisciplinary team comprised of representatives from almost every department of the hospital. Therapy is dangerous and requires many resources. According to a new Indian survey, 24.3 per cent of patients left the hospital against medical advice due to concerns about the expected cost, morbidity, and prognosis associated with surgery. Mucormycosis that develops in the post-COVID-19 environment strains a patient's family that is narrowly healing from a perilous viral infection.

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Bottom line

COVID-19 infection is associated with severe pulmonary disease and related alveolo-interstitial pathology. This can predispose a person to invasive fungal infections of the airways, sinuses, and lungs. Additionally, innate immunity is altered as a result of COVID-19-associated immune dysregulation, as shown by reduced T cells, including CD4 and CD8 cells. In the future, all clinicians, including ophthalmologists, should be aware of the possibility of fungal infections such as mucormycosis developing in patients with COVID-19 disease, particularly in those with comorbid conditions and on immunosuppressive drugs.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.