Dear Professor,

Thanks for your answer on my questions.

Aggressive steroids especially in diabetic patients

Thanks professor

https://www.researchgate.net/post/Antibiotics_in_COVID-19_are_they_really_helping_us_or_harming_us_Need_to_re-think

Nowadays, cases of Mucor-mycosis are on rise in COVID patients. Risk factors are diabetes, old age, steroids etc. Out of these risk factors diabetes and old age are unmodifiable risk factors and steroids are the sole drugs which has shown mortality benefit in COVID-19 pneumonia. In short, as of now we cannot modify any of them.

What about antibiotics? Every prescription of COVID-19 patient, whether mild symptoms or severe symptoms is having antibiotics on the top.

What’s the rational for using antibiotics in COVID-19?

Ans: Antibiotics are being prescribed to prevent secondary bacterial infection because COVID-19 itself is an immunocompromised state and almost every COVID-19 sick patient is getting steroids which can further suppress immunity increasing the chances of secondary bacterial infection.

Facts:

1. Antibiotics cannot kill viruses, so they are not the definite treatment for viral pneumonia.

2. Antibiotics can kill normal bacterial flora in our body and then in such ‘immunocompromised state’ fungi can take their place.

3. A retrospective small scale cohort study hypothesized that it’s ‘clinician’s anxiety’ over the possibility of concurrent or developing bacterial respiratory tract infections driving them to use antibiotics in cases of viral pneumonias.

Pitfalls of this study were, its small scale and retrospective nature. (Infect Control Hosp Epidemiol. 2010 November; 31(11): 1177–1183).

4. A study published in 2018 concluded that microbiota i.e., normal gut microbial flora drives an interferon (IFN) signature in lung stroma cells. These increased IFN signature impedes early influenza virus replication in lung epithelia. But the use of antibiotics reduces the IFN signature and facilitate early virus replication. (Bradley et al., 2019, Cell Reports 28, 245–256).

5. Even there is no data which shows that acute high doses of steroid use are associated with increase risk of bacterial infections.

Gibbs RC et al studied influence of prophylactic use of antibiotics on the incidence of staphylococcic infection in patients treated with steroids in the dermatological wards. They concluded that prophylactic addition of antibiotics certainly does not always succeed in preventing infection and may, in some cases, convert a potential hazard into reality. (JAMA. 1960;172(1):11-12. doi:10.1001/jama.1960)

RCTs of corticosteroid use in rheumatic diseases have not reported an increased risk of infection but observational studies have found a consistently elevated risk of infections (both serious and opportunistic). Of course, RCTs are considered more reliable when one has to draw some conclusion. (Rheum Dis Clin North Am. 2016 February; 42(1): 157–176.)

So, its time to re-think on extensive empirical antibiotics use.

Thanks for your good information

There are certain factors in COVID 19 patients which make them susceptible to mucor infection.

1. Diabetes- There are multiple ways described how the covid 19 virus can directly make the body insulin resistant, damage the beta cells of pancreas and reduce insulin secretion. The use of steroids adds fuel to the fire and therefore many previously non- diabetic individuals are having diabetes and at times are going into ketoacidosis.

2. Iron metabolism- During the cytokine storm the iron metabolism of the body is possibly affected, the fungi thrives on iron.

3. Immunosuppression- High dose of steroids and the virus itself damages the immune system.

All these make a covid 19 patient an ideal environment for mucor.

Possible sources of mucor- bed linen, contaminated humidifiers and oxygen sources.

The current trend shows younger population getting affected possibly because of the vaccination status.

Thank you so much to all expert for given your opinion

Mucorales causing colonisation of para-nasal sinuses is common in India, possibly due to the hot and humid weather. The fungus lies dormant in most individuals for the entirety of their lives. Possible factors that are a breeding ground for invasive disease are:

1. Uncontrolled Diabetes Mellitus, especially Diabetic Ketoacidosis. Diabetes with good control also leads to a higher risk, although less.

2. Steroid use, specially high doses upto Pulse therapy.

3. Immunosuppression, including possible chronic granulomatous disease/phagocytosis defects.

https://www.researchgate.net/publication/340585432_Case_of_mucormycosis_of_mandible_after_self-extraction_of_teeth_incidentally_detected_to_have_chronic_granulomatous_disease_Case_report_and_literature_review

4. Possible colonisation of central oxygen line, infrequent changing of water in the humidifier chamber.

5. Widespread use of broad spectrum antibiotics and at time prophylactic anti-fungals, that do no act against mucor, leading to selection pressure and promoting growth of Mucorales, by eliminating the competing normal flora.

What we can do best is to avoid unnecessary steroid use, especially in mild COVID, use judicious doses, ensure regular changing of water in the humidifier chamber, and maintain euglycemia with strict monitoring of blood sugars and insulin as needed.

Shubham Agarwal Thanks for your points

The above points cover most risk factors

Some more

1. people got no hospital beds in second wave in India . So steroids were often taken in unsupervised doses at home with no sugar monitoring .

2. Similarly there was no monitoring post covid/ hospital visit.

3. Some argue reusing moist masks, excessive steam, industrial oxygen use...all to contribute....but no evidence so far

Several,

1. Immunocompromised state due to several causes - Diabetes, steroids, post-viral (COVID-19) infection.

2. Mucor thrives on Iron. Serum Ferritin is raised in many patients of COVID-19

3. Mucor also thrives on Zinc. Keep in mind the prescriptions of Zinc supplements have surged during the pandemic, many patients may be on supra doses

Thanks all expert

Unfortunately there are patients who do have any of the factors mentioned above.

So covid per se having immunological alteration cannot be ruled out

Please have a look at this useful RG link.

Article SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids—An Unh...

Arvind Singh, Thanks. Thank you Pranav

Mucormycosis has surged in India recently, primarily affecting people recovering from COVID-19. This type of fungal infection is extremely rare and may be affecting people whose immune systems have been damaged by the coronavirus. The use of steroid drugs in these patients may partially explain some of the surge, while the immune-compromised state of COVID-19 patients could explain others. https://www.healthline.com/health-news/black-fungus-is-appearing-in-people-with-covid-19-what-to-know

Check https://indianexpress.com/article/lifestyle/health/covid-19-mucormycosis-fungal-infection-symptoms-treatment-causes-7286157/lite/

Uncontrolled diabetes, excessive use of corticosteroids for immunosuppression, and long-term stays in the intensive care unit are the common causes behind rise of mucormycosis (black fungus) in COVID-19 patients.

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

May be the the method of oxygen generation for cylinders to store oxygen.

Find our observations based on limited experience on the same here: Article COVID-19 associated Rhino-orbital Mucormycosis: a Single Cen...

Thanks to all

Multifactorial

1. Abuse of corticosteroids

2. Uncontrolled Hyperglycemia

3. COVID-19 altered immunoparalysis

4. ? Genetic susceptibility

5. ? Environmental factor.

and lack of early suspicion and diagnosis

Thanks to everyone for giving your suggestion and points in my important questions. Thank you so much @Chinaza Godswill Awuchi

Steroid abuse

lack Of proper standard of hygiene

environmental factor..

Hyperglycemia is much more important than immunocompromised state here. Mucormycosis doesn’t affect HIV positive individuals as much as diabetics.

Reasons for mucormycosis epidemic could be:

1. Diabetes/ elevated blood dugar levels are the biggest risk factors for mucormycosis.

2. Use of steroids: this reduces immunity and also elevates blood sugar levels and as I have said in previous point this (blood sugar) is the most important risk factor for mucormycosis.