The document discusses mucormycosis, a fungal infection caused by exposure to mucor molds. It provides details on COVID-19 associated mucormycosis infections, including risk factors like steroid use in severe COVID cases. The summary discusses the epidemiology and clinical manifestations of mucormycosis, as well as challenges in diagnosis. Standard diagnostic methods outlined include tissue biopsy, culture, and microscopy of samples to detect fungal hyphae. Early diagnosis and treatment are important to manage mucormycosis and reduce mortality.

1. COVID 19
Associated Fungal infections
Dr.T.V.Rao MD
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 1

2. I am Greatful to all @
School of Public Health
SRM University Sikkim
•Hon Professor Dr C H Satish Kumar
Vice Chancellor
• HonDr Govind Pratap Singh Associate
Dean ( BS)
•Dr Toms K. Thomas Head School of
Public Health
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 2

3. Caution Before you see the file
•Information on COVID-19 is rapidly
changing, sometimes daily. Refer to
reliable sources such as the CDC,
OSHA, NIOSH, State Health
Departments and peer reviewed
science publications.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 3

4. MICROBES HUNTING MAN
TRUE OR FALSE ???
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 4

5. What is Coronavirus disease
(COVID-19)
• Coronavirus disease (COVID-19) is an infectious
disease caused by a newly discovered coronavirus.
Most people infected with the COVID-19 virus will
experience mild to moderate respiratory illness
and recover without requiring special
treatment. Older people, and those with
underlying medical problems like cardiovascular
disease, diabetes, chronic respiratory disease, and
cancer are more likely to develop serious illness.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 5

6. What Are Coronaviruses
•Coronaviruses (CoVs) are a highly diverse family
of enveloped positive-sense single-stranded RNA
viruses. They infect humans, other mammals and
avian species, including livestock and companion
animals, and are therefore not only a challenge
for public health but also a veterinary and
economic concern.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 6

7. Structure of Coronavirus
• The coronavirus virion consists of
structural proteins, namely spike (S),
envelope (E), membrane (M),
nucleocapsid (N) and, for some
betacoronaviruses, haemagglutinin-
esterase. The positive-sense, single-
stranded RNA genome (+ssRNA) is
encapsidated by N, whereas M and E
ensure its incorporation in the viral
particle during the assembly
process. S trimers protrude from the
host-derived viral envelope and
provide specificity for cellular entry
receptor
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 7

8. Viral tropism and pathogenicity.
• The initial steps of coronavirus infection involve the
specific binding of the coronavirus spike (S) protein
to the cellular entry receptors, which have been
identified for several coronaviruses and include
human aminopeptidase N (APN; HCoV-229E),
angiotensin-converting enzyme 2 (ACE2; HCoV-NL63,
SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase
4 (DPP4; MERS-CoV). The expression and tissue
distribution of entry receptors consequently
influence viral tropism and pathogenicity.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 8

9. How the COVID 19 Spreads
•COVID-19 virus spreads
primarily through droplets
of saliva or discharge from
the nose when an infected
person coughs or sneezes,
so it’s important that you
also practice respiratory
etiquette
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 9

10. Learning from the Past
Influenza 1918
• Respiratory viral infections
predispose patients to co-
infections and these lead to
increased disease severity and
mortality. Most fatalities in the
1918 influenza outbreak were
due to subsequent bacterial
infection, particularly with
Streptococcus pneumoniae.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 10

11. Viral Infections associated with
secondary Bacterial infections
•Poor outcomes in the
2009 H1N1 influenza
pandemic were also
associated with
bacterial co-infections,
although few studies
captured these data.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 11

12. Rapid diagnosis of Associated Infections
with Covid 19 Saves many lives
• Rapid characterisation of
co-infection is essential in
the management and
treatment of the most
severe COVID-19 cases,
could help to save lives, and
will improve antimicrobial
stewardship throughout the
course of the pandemic.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 12

13. Opportunistic fungal Infections
• Mucormycosis is the
third invasive mycosis in
order of importance
after candidiasis and
aspergillosis and is
caused by fungi of the
class Zygomycetes. The
most important species
in order of frequency is
Rhizopus arrhizus
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 13

14. Identification of Mucor
Infections
• Identification of the agents
responsible for
mucormycosis is based on
macroscopic and
microscopic morphological
criteria, carbohydrate
assimilation and the
maximum temperature
compatible with its growth.
• Image source NEJM
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 14

15. What is Mucormycosis
• Mucormycosis is an aggressive
opportunistic fungal infection, also
known as phycomycosis and
zygomycosis. Although
mucormycosis can affect other
parts of the body such as the lungs
and gastrointestinal tract,. It is
caused by organisms of the family
Mucoraceae (including the genera
Mucor, Absidia, and Rhizopus)
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 15

16. Need the Multi disciplinary infections
management
• Guidance on the complex
multidisciplinary
management of infections
caused by these pathogens
has the potential to improve
prognosis. Management
routes depend on the
availability of diagnostic and
therapeutic options.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 16

17. Need Emergency Diagnosis
• Timely diagnosis is paramount
in cases of mucormycosis.
Persons with suspected rhino
cerebral disease should
undergo emergent computed
tomography (CT) imaging of
the paranasal sinuses and an
endoscopic examination of
their nasal passages with
biopsies of any suggestive
lesions.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 17

18. Where we stand in Emergency
Diagnosis of Fungal Infections ?
Medical Colleges ?
Private Laboratories
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 18

19. 29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 19

20. Intended Learning
outcomes
To be aware of the epidemiology of mucormycosis
To understand the pathophysiology of mucormycosis
To be familiar with different clinical manifestations of mucormycosis
To be aware of the available management options for mucormycosis
To be aware of the complications and prognosis of mucormycosis
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 20

21. Source of Fungal Infections
• Mucormycosis is a rare fungal
infection caused by a group of
molds called Mucoromycotina
found in soil and decaying
organic matter.
• Mucormycosis infection
occurs in two ways: when
people inhale fungal spores,
as in the pulmonary or sinus
form; and cutaneous, when
fungus
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 21

22. Clinical spectrum of mucormycosis
• Rhino-cerebral mucormycosis Brain
and nasal sinuses
• Most common
• Pulmonary mucormycosis
• Cutaneous mucormycosis
• Gastrointestinal mucormycosis
• Disseminated mucormycosis
• Isolated renal mucormycosis Kauffman CA. Clin Infect Dis 2004;39:588-90.
Roden et al. Clin Infect Dis 2005;41:634-53.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 22

23. Scientific approaches in Mucormycosis
•The entity of mucormycosis was introduced at the
ECIL 3 (25-26 September 2009, Juan-les-Pins,
France) and brought together a panel of 57 expert
hematologists, oncologists, microbiologists,
infectious disease specialists and clinical trial
investigators from across Europe. This is the first
time the ECIL group addresses a topic where there
are no randomized studies to be analyzed.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 23

24. Mucormycosis triggered by
•Doctors believe
mucormycosis, which has an
overall mortality rate of
50%, may be being triggered
by the use of steroids, a life-
saving treatment for severe
and critically ill Covid-19
patients.
• TOTAL MISSUE OF
ANTIBIOTICS???
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 24

25. Aetiology: Several genera of Phycomycetes
• Common
• Rhizopus spp.
• ~70% of rhinocerebral mucormycosis cases
•Mucor spp.
• Rhizomucor spp.
• Rare
• Apophysomyces spp.
• Cunninghamella spp.
• Lichtheimia (Absidia) spp.
• Saksenaea spp.
Kauffman CA. Clin Infect Dis 2004;39:588-90.
Roden et al. Clin Infect Dis 2005;41:634-53.
Binders et al. Clin Microbial Infect. 2014;6:60-6
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 25

26. Environmental source of Fungi
•The fungus that causes
the disease is ubiquitous
in nature and is found in
soil and on decaying
vegetation. Because the
fungus is so widespread,
humans are exposed to
it on a regular basis
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 26

27. Spores of the Fungus are Inhaled
But do not produce in Normal healthy people
…
• The spores of the fungus
are inhaled through the
mouth and nose, but
infection rarely occurs in
a person with an intact
immune system because
macrophages
phagocytize the spores
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 27

28. What is black fungus?
Is it right Call as Black fungus
• t's caused by a group of
molds, called
mucormycetes.
Individuals are infected
after inhaling fungal
spores found naturally in
India's environment and
so
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 28

29. NAMING THE FUNGAL INFECTIONS BY COLORS
IS IT RIGHT OR WRONG ???
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 29

30. Immunocompromised patients are Highly
susceptible to fungal Infections
• However, an
immunocompromised
individual is unable to
mount an effective immune
response against the
inhaled spores; thus,
germination and hyphae
formation occur and
infection develops, most
commonly in the sinuses
and lungs.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 30

31. Clinical manifestation:
Rhinocerebral mucormycosis
• Unilateral headache - behind the eye
• Facial pain
• Eye swelling (Proptosis) + visual
disturbance
• Necrotic lesions on the hard palate or
nasal mucosa
• ENT symptoms
• Nasal congestion
• Black discharge
• Acute sinusitis
• Epistaxis
• Systemic symptoms: fevers
Wali et al. J Infect Public Health. 2012;5:116-26.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 31

32. Clinical manifestation – Disseminated
• Disseminated disease stems from
pulmonary focus
• Spread is haematogenous
• Deferoxamine therapy is the most
significant risk factor for
disseminated disease
• Manifestation:
• Headache
• Fever
• Visual disturbance
• Altered mentation Sarrami et al. Int J Prev Med. 2013; 4: 1468–1471.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 32

33. Mucormycosis, dubbed
"black fungus
•Mucormycosis, dubbed
"black fungus", is caused
by a mould found in soil
and in decaying organic
matter like rotting leaves,
according to the US
Centers for Disease
Control and Prevention
(CDC).
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 33

34. Diagnosis and testing for
Mucormycosis
• Laboratory personal perform a tissue
biopsy, in which a small sample of
affected tissue is analyzed in a
laboratory for evidence of
mucormycosis under a microscope or
in a fungal culture. You may also
need imaging tests such as a CT scan
of your lungs, sinuses, or other parts
of your body, depending on the
location of the suspected infection.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 34

35. Where does black fungus
come from?
• Mucormycosis or black fungus is a
complication caused by a fungal
infection. People catch
mucormycosis by coming in
contact with the fungal spores in
the environment. It can also
develop on the skin after the
fungus enters the skin through a
cut, scrape, burn, or other types
of skin trauma
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 35

36. STANDARD METHODS
TO DIAGNOSE
MUCORMYCOSIS
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 36

37. Diagnosis of Mucormycosis
• The diagnosis of mucormycosis
is challenging and treatment
should start as early as
possible in order to decrease
mortality. No circulating
antigen detection test (similar
to galactomannan detection
for invasive aspergillosis) is
available for the diagnosis of
mucormycosis
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 37

38. Microscopic examination
•Demonstration of
hyphae in clinical
samples by direct
microscopy is important
because it is rapid and
highly suggestive of
disease.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 38

39. What we can do with existing facilities in
teaching Hospital and Private labs too
• It can detect the actual
assimilation stage of
infection. Dextrose
Sabourauds Agar medium
is mostly applicable for
fungal growth following a
period of growth with
appropriate time and
temperature.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 39

40. Basic staining methods
• Haematoxylin and Eosin
stain helps to detect aseptate
broad fungal hyphae and
shows cytoplasm stained
pink-orange and nuclei
stained with dark blue or
purple. Lacto phenol cotton
blue staining is able to detect
mucor sporangium with
sporangiophore
• Source RSNA
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 40

41. Diagnosis: Histopathology
Non-septate hyphae with right-angle branching
Guarner & Brandt. Clin Microbiol Rev. 2011;24:247-280
Septate hyphae with acute-angle branching
Agents of mucormycosis Aspergillus spp.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 41

42. Processing's of Specimens for Mucormycosis
• The material taken from biopsies
should be carefully managed so
as not to be crushed because
zygomycetes are fragile, and
culture may thus remain
negative. Growth is rapid and
usually occurs during incubation
for 24 h at 25-37°C. Culture of a
sterile site confirms
mucormycosis infection and
allows precise genus and species
identification
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 42

43. Utility of Blood cultures ????
• Blood cultures are almost
always negative and their
positivity should evoke the
suspicion of contamination.
Similarly, agents of
mucormycosis are rarely
present in the cerebrospinal
fluid even during central
nervous system infections.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 43

44. Observation after treatment with Potassium
hydroxide
need for Florescent Microscope
• Specimens can be observed
after treatment with potassium
hydroxide, staining with an
optical brightener (calcofluor
white), or with Gomori
methamine-silver Hyphae are
hyaline, non- or pauciseptate,
ribbon-like with a large
diameter (5-25 μm
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 44

45. Use of Special staining Methods
• When hyphae are
fragmented, a definitive
diagnosis of mucormycosis
can be difficult by direct
examination and culture is
required to confirm the
diagnosis. Tissue can be
stained with Gomori
methaminesilver or
Periodic-acid Schiff
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 45

46. Diagnosis needs Expertise
• Hyphae may be observed within
necrotic tissue with signs of
angioinvasion and infarction;
neutrophilic infiltrates or granuloma
formation may be present in
patients who are not
granulocytopenic or with more
chronic infection, respectively.
Occasionally,
immunohistochemistry with
commercially available
antizygomycete antibodies may help
in the diagnosis.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 46

47. Molecular Methods to identify fungi
•When cultures are
negative, molecular
identification from tissue
samples can confirm the
histological diagnosis.
However, at present, there
is no standardized method
available. Fresh or frozen
samples are preferred;
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 47

48. Recent advances in Diagnosis
• Molecular identification of agents
of mucormycosis can help to
confirm diagnosis and identify the
fungus to the genus and species
level. Different techniques have
been reported: DNA probes
targeting 18S subunit, ITS1
sequencing after polymerase
chain reaction (PCR) with pan-
fungal primers, 18S-targeted
semi-nested PCR and real-time
PCR targeting cytochrome b gene.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 48

49. Prevention in all work settings
• Wash hands after removing gloves or when soiled.
• Wear a mask.
• Keep common surfaces such as telephones, keyboards clean.
• Avoid sharing equipment if possible.
• Minimize group meetings by using phone, email, and avoid close contact
when meetings are necessary.
• Consider telework.
• Limit unnecessary visitors to the workplace.
• Maintain your physical and emotional health with rest, diet, exercise, and
relaxation.
49

50. Rapid Diagnosis with Imagining techniques
CT scan saves lives continues to be most
preferred tool
•You may also need
imaging tests such as
a CT scan of your
lungs, sinuses, or
other parts of your
body, depending on
the location of the
suspected infection.
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 50

51. 51
• Preparing for the threat.
• Implementing preventive measures.
• Implementing the continuity of operations plan.
• Managing business recovery post-epidemic.
PUBLIC HEALTH PERSONAL HAVE A GREAT ROLE TO
PLAY

52. WHAT ALL WE SAY COVID 19 MADE
US STUDENTS OF MEDICNE
29-05-2021 Dr.T.V.Rao MD @ Covid19 and Mucourmycosis 52

53. References
• Diagnosis and treatment of mucormycosis in patients with
hematological malignancies: guidelines from the 3rd European
Conference on Infections in Leukemia (ECIL 3)
• CDC resources on Covid 19 and Mucormycosis
• Google resources on Covid 19 and Mucormysocis
• NIH We resources
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