Covid-19 and Mucormycosis

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients.

While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor.

Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis.

Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

The symptoms of mucormycosis depend on where in the body the fungus is growing. The most common presentation is a sinus infection (sinusitis) that is accompanied by nasal congestion, nasal discharge, and sinus pain. A fever and headache may also occur.

Disease prevention

Prevention of COVID-associated mucormycosis needs to focus on addressing the underlying risk factors:

• aiming for better glycemic control in those with diabetes,
• appropriate use of systemic corticosteroids and
• prevention of unnecessary use of antibiotic, antifungal and other immunomodulators.

Treatment

Mucormycosis is difficult to treat. It may sometimes requires both intravenous antifungal therapy and surgical excision, thus necessitating a multidisciplinary team approach in a facility setting. 

Liposomal amphotericin B is the drug of choice and needs to be initiated early. Other antifungals like posaconazole, or isavuconazolehave also been described for treatment. 

CITATIONS:

//pubmed.ncbi.nlm.nih.gov/33544266/

//www.who.int/india/emergencies/coronavirus-disease-(covid-19)/mucormycosis

There are increasing case reports of rhino-orbital mucormycosis in people with coronavirus disease 2019 (COVID-19), especially in India. Diabetes mellitus (DM) is an independent risk factor for both severe COVID-19 and mucormycosis. We aim to conduct a systematic review of literature to find out the patient's characteristics having mucormycosis and COVID-19.

An unholy trinity of diabetes, rampant use of corticosteroid in a background of COVID-19 appears to increase mucormycosis. All efforts should be made to maintain optimal glucose and only judicious use of corticosteroids in patients with COVID-19.

//www.sciencedirect.com/science/article/pii/S1871402121001570

Mucormycosis is a fungal infection which is spread through inhalation of spores or mucormycetes (1).  COVID-19 Associated Mucormycosis (CAM) has caused a rapid increase in the number of cases worldwide, with majority being reported in India. According to ICMR, an increased risk of mucormycosis is associated with multiple conditions (Diabetes, weak immune system due to use of steroids, prolonged ICU/hospital stay, co-morbidities / post organ transplant / cancer, Voriconazole therapy) in COVID-19 patients (2). Considering this, it is imperative to reflect upon the measures to combat the additional crisis of mucormycosis. This paper summarizes the preventive strategies that can be employed for management of COVID-19 related mucormycosis (3).

References

1. //www.gavi.org/vaccineswork/black-fungus-epidemic-hitting-covid-19-patients-india&source=gmail&ust=1624418176005000&usg=AFQjCNGjkGIEwPA4a-8GfaVGmGFGR3km_ A"> //www.gavi.org/vaccineswork/black-fungus-epidemic-hitting-covid-19-patients-india
2. //pib.gov.in/PressReleseDetailm.aspx?PRID%3D1718501&source=gmail&ust=1624418176005000&usg=AFQjCNEtFoUJxZWv6ShybFAZY8chVdC9T Q"> //pib.gov.in/PressReleseDetailm.aspx?PRID=1718501
3. //pmj.bmj.com/content/early/2021/06/08/postgradmedj-2021-140537&source=gmail&ust=1624418176005000&usg=AFQjCNFyWEumQwG3THX_s2fQR8g7KYAIc A"> //pmj.bmj.com/content/early/2021/06/08/postgradmedj-2021-140537

What is Mucormycosis?

Mucormycosis is a serious and rare condition that is caused by a group of moods called Mycocytes. The fungus is found throughout the environment for example in soil, decaying organic matter such as leaves , compost piles, rotten wood etc.

people get infected with mucormycosis if they they come in contact with the fungal spores in the environment. For example : If anyone inhales the fungal spores it causes infection of sinuses and lungs. Such infections are common Among Immune-compromised individuals, Person on Steroid treatment or any condition that lowers the ability of the body to fight against infection.¹

Types of Mucormycosis:

1. Rhinocerebral mucormycosis : (sinus and brain) commonly seen in patients with diabetes and kidney transplant.
2. Pulmonary Mucormycosis : Commonly found in people with Cancer , Post organ transplant and stem cell therapy.
3. Gastrointestinal mucormycosis : commonly seen in young children and rarely in adults. Especially Premature Infants, in less than 1 month of age, due to antibiotics treatment, surgery, medications that lower the ability of the infant’s body to fight the infection.
4. Cutaneous Mucormycosis : (Skin) This typr of mucormycosis occurs when the skin ruptues and contacts the fungus like in skin trauma, after surgery (over suture site), burns. This is the common form og fungal infection among those who have good immunity.
5. Disseminated mucormycosis : This type occurs when the infection spreads through the blood stream and affects other parts of the body. It can affect brain, spleen , heart and skin to name a few.

Types of fungi that cause Mucormycosis are:

• Rhizopus species.
• Mucor species
• Rhizomucor species
• Syncephelastrum species
• Cunnighmella bertholleltiae
• Apophysomyces species
• Lichtheimia species.

The symptoms of Mucormycosis depends on the site of infection.

Rhinocerebral infection symptoms include:

• Headache
• One- sided facial swelling
• Nasal /sinus congestion
• Black lesions spotted on nasal bridge or upper side of mouth which becomes severe very quickly.
• Fever

Pulmonary Mucormycosis symproms include:

• Fever
• Cough
• chest pain
• Shortness of breath.

Cutaneous mucormycosis symptoms include

• Looks like blisters on skin or ulcers.
• Nausea and vomiting
• Abdominal pain
• Gastrointestinal bleeding

Disseminated mucormycosis symptoms are difficult to define as it occurs most commonly among people who are already suffering from other medical conditions. If it is disseminated infection in brain the patient can develop symptoms like altered mental status or coma.

COVID-19 and mucormycosis

Coronavirus disease 2019 (COVID-19) caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with range of opportunistic bacterial and fungal infection . aspergillosis and candida have been reported as the main fungal pathogens causing infection among COVID patients. Recently many cases of Mucormycosis has been reported among COVID patients world wide and in India.

Following factors are possible causes for mucormycosis among COVID-19 affected patients:

Ideal environment in lungs for the growth of Mucorales spores – that is

• hypoxia – low oxygen levels
• High glucose (among diabetes patients, new-onset hyperglycemia/steroid induced hyperglycemia )
• acidic medium- metabolic acidosis , diabetic ketoacidosis
• high iron levels (increased ferritins)
• decreased phagocytic activity of white blood cells due to immunosuppression .
• prolonged hospitalization with ot without ventilation.

World wide prevalence of mucormycosis varied between 0.005 to 1.7 per million population, While its prevalence is 80 times higher in India – 0.14 per 1000. This number tells us that India has undoubtedly highest number of cases of mucormycosis. The reason for such high number of mucormycosis cases in India can be attributed to the fact that India has second largest number of Diabetes Mellitus cases in the world. Importantly DM has been the most common cause of the mucormycosis. DM is the leading risk factor for mucormycosis and has a mortality rate of 46%.

Exposure to corticosteroids is also linked to Opportunistic infections. Even short span of exposure to the Corticosteroid treatment during COVID -19 coupled with DM has been linked to mucormycosis.

A study depicting the systemic review of cases of mucormycosis and COVID-19 worldwide and India. The study aimed at conducting systemic review of literature to understand the characters of having mucormycosis and COVID-19.²

The database used were- PubMed and Google scholar. The results of the review were as follows: Out of 101 cases of mucormycosis in patients with COVID-19  , 82 were from India and 19 from other parts of the world. Mucormycosis was predominantly seen in males – 78.9% among both the groups of active (59.4%)or recovered (40.6%). Pre-existing Diabetes Mellitus was present in 80% of the cases. Concomitant ketoacidosis (DKA) was present among 14.9% cases. Corticosteroid intake for treatment was recorded in 76.3% of cases. Mucormycosis including nose and sinuses was followed by Rhino-orbital mucormycosis. Mortality rate was 30.7%.

To conclude it is the Trinity of Diabetes, treatment with corticosteroids in a background of COVID -19  caused mucormycosis, mostly Rhino-orbital in COVI-19 pandemic period. Care must be taken in controlling sugar levels among the COVID patients and judicious use of corticosteroids with regular monitoring is required. Prolonged ventilatory support should also be avoided as much as possible.

References

1. Richardson M. the ecology of the Zygomycetes and its impact on environmental exposureexternal icon. Clin Microbiol Infect. 2009 Oct;15 Suppl 5:2-9
2. Awadhesh Kumar Singh, Ritu Singh, Shashank R Joshi, Anoop. Misra, Mucormycosis in COVID-19 : A systemic review of cases reported worldwide and in India, science direct, DOI: //doi.org/10.1016/j.dsx.2021.05.019

COVID-19 and MUCORMYCOSIS:

    ☆ Mucor is fungus commonly seen in environment.

     ☆ It causes disease when immunity is low.

      ☆ It occurs during COVID-19 infection (or) few weeks after 

 recovery from COVID-19. 

        ☆ It also occurs in patients with uncontrolled diabetes

Symptoms:

        • Nose and sinuses infection 

        • Headache, nasal obstruction 

        • Loss of sensation on face

        • Eye swelling, double vision, drooping eyelids.

COVID 19 and Mucormycosis

COVID has been a massive disaster from the year of 2019. Some claims it to be a BioWar while others say it has natural. But still researches are being carried out to find the exact cause for the outbreak.

Initially it has been said that Covid-19 had no risk effects on HIV carriers but resend studies says that Covid-19 has a severe effect on people with HIV infection. This has disrupted the treatment service for HIV.

India is facing problems in providing the immediate medication due to less availability of oxygen concentrators, ventilators, oxygen cylinders. This has provoked the hashtags such as #Covid19IndiaHelp. The government of India is providing vaccines to nearby health centre but people of India have great hesitance towards vaccination.

By following the rules and regulation the effective spreading of Covid-19 can be decreased.

Mucormycosis is a fungal infection that affects the airway. It is also airborne disease. Patients with uncontrollable diabetes are likely to be affected severely.

Citation

Juan Ambrosioni, PhD , José Luis Blanco, PhD
//doi.org/10.1016/S2352-3018(21)00070-9

George Petrikkos, Anna Skiada, Olivier Lortholary, Emmanuel Roilides, Thomas J. Walsh, Dimitrios P. Kontoyiannis, Epidemiology and Clinical Manifestations of Mucormycosis, Clinical Infectious Diseases, Volume 54, Issue suppl_1, February 2012, Pages S23–S34, //doi.org/10.1093/cid/cir866

Mucormycosis and covid 19 riding the second wave in India

Mucormycosis or black fungus is a rare, fatal, and fungal disease caused by a group of molds which can lead to death if not treated adequately. The second wave in India has bought in the most cases of Mucormycosis which rose to a record high of 0.4 million on May 2021 and declined later. This accounted for 45 % of detected cases of Mucormycosis and 34 % of deaths globally in May 2021. Multiple states in India have declared it an epidemic.

The group at risk includes individuals who suffer from:

• uncontrolled diabetes
• use excessive corticosteroids
• Are severely immunocompromised due to diseases and conditions like cancer or AIDS
• Have undergone surgery and have cuts/wounds
• individuals who have recovered from severe covid 19 infections that were subjected to corticosteroids during the covid 19 treatment.

Symptoms of Mucormycosis

It depends on the site of the body the fungus is growing.

Symptoms of rhinocerebral (sinus and brain) mucormycosis include:

• One-sided swelling of face
• Headaches with or without Nasal or sinus congestion
• Black lesions on nasal bridge or upper inside of the mouth that quickly become more severe
• Fever

Symptoms of pulmonary (lung) mucormycosis include:

• Fever
• Pain in chest
• Cough
• Shortness of breath

Cutaneous (skin) mucormycosis presents blisters or ulcers, and the area affected may turn black. Other symptoms include pain, redness, warmth, or swelling around a wound.

Symptoms of gastrointestinal mucormycosis include:

• Nausea
• vomiting
• Abdominal pain
• Gastrointestinal bleeding

Disseminated mucormycosis affects people suffering other medical conditions, and can result in mental status changes or coma in the affected patients.

One must therefore identify these symptoms and report to a doctor immediately io suspicion for treatment.

Avoid direct contact with soil or water-damaged areas where this fungus may be found.

Wear an N95 mask if you need to visit such places.

Visit your health care provider/physician if you are a high-risk case for further treatment and prevention.

Maintain social distancing and regular hygiene measures while visiting crowded and susceptible areas.

//www.bbc.com/news/world-asia-india-57027829

//www.cdc.gov/fungal/diseases/mucormycosis/symptoms.html

//www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00265-4/fulltext

Mucormycosis is a very rare infection. It is caused by exposure to mucor mould which is commonly found in soil, plants, manure, and decaying fruits and vegetables. The reason for mucormycosis in COVID-19 patients includes uncontrolled diabetes and usage of corticosteroids for immunosuppression. Steroids reduce inflammation in the lungs for Covid-19 and appear to help stop some of the damage that can happen when the body's immune system goes into overdrive to fight off coronavirus. But they also reduce immunity and push up blood sugar levels in both diabetics and non-diabetic Covid-19 patients. Mucormycosis is mainly treated by using amphotericin B

Mucormycosis, the most treacherous post COVID-19 fungal infection is less common in developed countries than in developing countries. 

While global attention is focused on COVID-19, the Indian subcontinent is overburdened by Mucormycosis, which emerged as a new manifestation of coronavirus roughly in 14 out of 1,00,000 patients.

Hyperglycemia in uncontrolled diabetes is the strongest predisposing factor for Mucormycosis, besides long-stay of COVID patients in the ICU.

An important virulence trait of Mucormycosis is the ability to acquire iron from the host, which is essential for its growth. The amplified use of corticosteroids and immunosuppressants has enhanced its virulence, making the patients vulnerable to Mucormycosis and leads to cascade of events such as:

• Loss of eyesight
• Hearing impairment
• Thrombosis
• Tissue necrosis
• Brain cell loss

Treatment principles of Mucormycosis is of multi-model approach:

• Injection of anti-fungal agents
• Surgical debridement
• Timely dosage of adjuvant therapy

Ultimately, recovery is a challenge.

Posted by: @ashishjoshi

Please share your thoughts about Covid-19 and Mucormycosis, the black fungus.

Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of molds called mucormycetes. These molds live throughout the environment. Mucormycosis mainly affects people who have health problems or take medicines that lower the body's ability to fight germs and sickness.

Mucormycosis, a potentially life-threatening fungal infection, is adding to India’s COVID-19-related death toll with reported cases in the 2nd wave which typically affects patients recovering from COVID-19 who are immuno-compromised due to COVID or may be by the use of steroids and/or concomitant diabetes. In recent times, there seems to be a few cases showing oral manifestations though rarely diagnosed but other than the usual symptoms seen in SARS-COV-2 positive patients, mucormycosis of oral cavity presents with fungal white patches on tongue. In some cases ulcers in mouth and gingivitis have also been reported with loosening of anterior teeth and white hairy scrapable patched on buccal mucusa.

Hyperglycemia in patients with diabetes creates an even more favorable environment. In addition, COVID-19 damages and weakens the superior respiratory tract and the eye, increasing susceptibility to fungal infection. Another contributing factor is the use of antibiotics, also commonly prescribed in patients with COVID-19 to fight secondary infections. The symptoms of mucormycosis can range from bad breath to loosening of teeth. It is very necessary that treating doctor should advise their patients, who have recovered from Covid-19, to go for regular oral and dental check-ups for at least a month esp for the patients who have diabetes. An infection in the mouth can increase the viral load of the disease. To tackle this combo fight against COVID and mucormycosis, one should keep their sinuses clear, steam inhalation is recommended. Nasal irrigation with betadine sloution can help to prevent infections. Besides these, the recovered patients must take a high protein, low sugar diet and take Vitamins A, E and B-Complex.

There is a need to address this issue and fill the gaps in terms of advocacy for such infections to the remote areas and tribals, which I feel SMAART tracker informatics platform should incorporate this informagraphics with basic preventive and referral services pan India.

COVID-19 caused by SARS CoV-2 has been sweeping across the globe. Although COVID-19 itself is associated with several risk factors for a fungal infection called mucormycosis, it has been observed that COVID-19 patients with diabetes are at an even greater risk of acquiring this secondary infection. 

Mucormycosis( previously called zygomycetes) is a potentially lethal but rare fungal infection caused by a group of molds called mucormycetes. It often affects immunocompromised individuals, particularly those with diabetes mellitus, leukemia, lymphoma, previous stem cell transplant, and systemic corticosteroid use.

Mucormycosis presents itself as either a respiratory or a skin infection. 

Signs of respiratory infection may include:

• Cough
•  Fever 
• Headache
• Nasal or sinus congestion
• One-sided facial swelling

With a skin infection, mucormycosis could be manifested in the form of:

• Blackened skin tissue
• Blisters
• Redness
• Swelling and tenderness
• Ulcers

People with conditions such as burns, cuts, cancer, recent organ transplant, AIDS, and untreated diabetes are at a higher risk of contracting this infection.

If left untreated, mucormycosis could cause brain infection, paralysis, pneumonia, seizures, or even death.

The first step in treating mucormycosis is receiving IV antifungal medications such ad amphotericin B, posaconazole, isavuconazole.

Often, surgery is done to remove the infected tissue.

COVID-19 associated mucormycosis (CAM) has been seen increasing rapidly worldwide and India is reporting majority of the cases.

- The severity of Mucor infection/ Black Fungus is largely dependent on the patient’s immunity and general health.

-COVID-19 has seen to worsen diabetes and also seen to cause diabetes in normal individuals who were non diabetic previously.

-The Covid 19 infection causes significant decrease in some types of white blood cells and thus decrease in immunity.

- Some medicationsused in treatement of Covid-19 like Steroids and Tocilizumab used for may worsen the immunity levels.

-In Covid –19 infection,high blood sugar levels, and immunosuppressive treatments are all present then the risk from infection increases.

 Mucormycosis / Black fungus

-Mucormycosis is not a new disease , commonly known as Black fungus

-It is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes. Mucor is a fungus which is normally present in the environment and in soil and it causes disease to those who have critically low immunity .

-It mainly affects people who are having low immunity or patients who are already infected with other diseases (high-risk group includes people with diabetes, solid organ transplantation, neutropenia, or iron overload )

-The risk is high for people living with HIV and those using immunomodulating drugs too.
-Cases of Mucor infection has seen a sudden increase during COVID-19 infection or weeks after recovery as they immunity is hampered during Covid-19

-It is rare but is a serious complication of COVID-19 infection with mucormycosis can cause loss of eye and may be life-threatening

-Alarming symptom for Mucormucosis generally start in Nose and me progress to the eye and the brain and it is an aggressive life-threatening infections requiring early diagnosis and treatment.

References used-

//covid.aiims.edu/mucormycosis-in-covid-19/

//www.who.int/india/emergencies/coronavirus-disease-(covid-19)/mucormycosis

//pubmed.ncbi.nlm.nih.gov/33463566/

Mucormycosis or which is also known as black fungus, is a serious but rare fungal infection, it will mainly effect people who are having lower immune system/response in their body. Mode of spread of infection is through contact with the fungal spores in the environment. Mucormycosis is seen in the people who are mainly effected with covid-19,as their immunity system is weakened. In India mainly during the second wave of covid-19 pandemic, high rise of mucormycosis cases are seen mainly due to the 1)unhygienic conditions of the hospitals/wards which resulted in spread of the fungal infection 2)Usage of single mask for many days/usage of masks which are contaminated also resulted in increase of spread of fungus 3)It is also seen in people with High usage of steroids (which are being used for treatment of covid-19)and also with uncontrolled diabetes.4)It is seen in people who are suffering with other Comorbities along with covid-19 which lead to the weakened immune response in their body.

Signs to watch out for :1)facial pain,2)fresh onset of headache especially post covid-19,3)nasal or sinus congestion,4)black lesions on upper inside of mouth,5)pain in eye, loss of vision .If left untreated it results in severe manifestations mainly causing structural damage. Now, currently people are becoming aware of the black fungus infection and they are visiting the hospitals during the initial stage which is preventing them from any further structural damage caused by it. Certain precautions/preventive measures should be followed in order to avoid the spread of the fungal infection ,the first and the foremost is to wear a mask(mostly N-95) ,maintain hygienic conditions, reduce the use of steroids , maintaining the level of blood glucose/sugar, taking any antifungal medications if prescribed.

Highly invasive nature of Mucormycosis, needs diagnostic tests that are efficient and less time consuming. Periodic checks post COVID-19  or during the course of hospitalization will ensure controlling the spread. Currently below are the available methods of diagnosis, 

1. Clinical diagnosis 

2. Routine laboratory diagnosis  

3. Applied molecular methods

4. Non invasive diagnostic methods

Diagnosis of mucormycosis is challenging. Histopathology, direct examination and culture remain the gold standard of diagnosis  although the molecular methods are improving. DNA in blood have shown promising results for earlier and rapid diagnosis and could be used as screening tests in high-risk patients, but have to be validated in clinical studies. Much needed, rapid methods that do not require invasive procedures, such as serology-based point-of-care, or metabolomics-based breath tests, are being developed and hopefully will be evaluated in the near future.

Here is a link to the article for details on the diagnostic tests - //pubmed.ncbi.nlm.nih.gov/33147877/