Mixed invasive fungal infections among COVID-19 patients

Document Type : Original Articles

Authors

1 Department of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, Indi

2 Department of Internal Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

3 Department of ENT, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

4 Department of Pathology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

10.18502/cmm.7.4.8407

Abstract

Background and Purpose: The healthcare system in India collapsed during the second
wave of the COVID-19 pandemic. A fungal epidemic was announced amid the pandemic with several cases of COVID-associated mucormycosis and pulmonary aspergillosis being reported. However, there is limited data regarding mixed fungal infections in COVID-19 patients. Therefore, we present a series of ten consecutive COVID-19 patients with mixed invasive fungal infections (MIFIs).
Materials and Methods: Among COVID-19 patients hospitalized in May 2021 at a
tertiary care center in North India, 10 cases of microbiologically confirmed COVID-19-
associated mucormycosis-aspergillosis (CAMA) were evaluated.
Results: All patients had diabetes and the majority of them were infected with severe
COVID-19 pneumonia (6/10, 60%) either on admission or in the past month while two
were each of moderate (20%) and mild (20%) categories of COVID-19; and were treated
with steroid and cocktail therapy. The patients were managed with amphotericin-B along with surgical intervention. In total, 70% of all CAMA patients (Rhizopus arrhizus with Aspergillus flavus in seven and Aspergillus fumigatus complex in three patients)
survived.
Conclusion: The study findings reflected the critical importance of a high index of
clinical suspicion and accurate microbiological diagnosis in managing invasive dual
molds and better understanding of the risk and progression of MIFIs among COVID-19
patients. Careful scrutiny and identification of MIFIs play a key role in the
implementation of effective management strategies.
 


 

Keywords


 1. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2
and COVID-19. Nat Rev Microbiol. 2021;19(3):141-154.
2. Cevik M, Kuppalli K, Kindrachuk J, Peiris M. Virology,
transmission, and pathogenesis of SARS-CoV-2. BMJ.
2020;371:m3862.
3. Werthman-Ehrenreich A. Mucormycosis with orbital
compartment syndrome in a patient with COVID-19. Am J
Emerg Med. 2021;42:264.e5-264.e8.
4. Moorthy A, Gaikwad R, Krishna S, Hegde R, Tripathi KK, Kale
PG, Rao PS, Haldipur D, Bonanthaya K. SARS-CoV-2,
Uncontrolled Diabetes and Corticosteroids—An Unholy Trinity
in Invasive Fungal infections of the maxillofacial region? A
retrospective, multi-centric analysis. J Maxillofac Oral Surg.
2021;6:1-8.
5. Hoenigl M. Invasive Fungal disease complicating coronavirus
disease 2019: When it rains, it spores. Clin Infec Dis.
2020;73(7):e1645-e1648.
6. Prakash H, Chakrabarti A. Epidemiology of mucormycosis in
India. Microorg. 2021;9(3):523-534.
7. Gangneux JP, Bougnoux ME, Dannaoui E, Cornet M, Zahar JR.
Invasive fungal diseases during COVID-19: We should be
prepared. J Mycol Med. 2020;30(2):100971
8. Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA,
Dannaoui E, Hochhegger B et al. Global guideline for the
diagnosis and management of mucormycosis: an initiative of the
european confederation of medical mycology in cooperation
with the mycoses study group education and research
consortium. Lancet Infect Dis. 2019;19(12):e405-e421.
9. Revision and Update of the Consensus Definitions of invasive
fungal disease from the european organization for research and
treatment of cancer and the mycoses study group education and
research consortium. Clin Infect Dis. 2020;71(6):1367-1376.
10. Management Protocol For Mucormycosis. 2021. Available from:
https://aiimsrishikesh.edu.in/a1_1/wp-content/uploads/2020/11/
MUCOR-Management-protocol_AIIMS-Rishikesh_Version-
1.0.cleaned.pdf
11. Arastehfar A, Carvalho A, van de Veerdonk FL, Jenks JD,
Koehler P, Krause R, Cornely OA, S Perlin D, Lass-Flörl C,
Hoenigl M. COVID-19 associated pulmonary aspergillosis
(CAPA)-from immunology to treatment. J Fungi. 2020;6(2):
91-101.
12. Bartoletti M, Pascale R, Cricca M, Rinaldi M, Maccaro A,
Bussini L et al. Epidemiology of invasive pulmonary
aspergillosis among COVID-19 intubated patients: a prospective
study. Clin Infect Dis. 2021; 73(11), e3606-e3614.
13. John, T.M.; Jacob, C.N.; Kontoyiannis, D.P. When Uncontrolled
Diabetes Mellitus and Severe COVID-19 Converge: The Perfect
Storm for Mucormycosis. J. Fungi 2021; 7:298-305.
14. Krüger W, Vielreicher S, Kapitan M, Jacobsen ID, Niemiec MJ.
Fungal-Bacterial Interactions in Health and Disease. Pathogens
(Basel, Switzerland). 2019;8(2):101-110.
15. Cox MJ, Loman N, Bogaert D, O'Grady J. Co-infections:
potentially lethal and unexplored in COVID-19. Lancet Microbe.
2020;1(1):e11.
16. Ichai P, Saliba F, Baune P, Daoud A, Coilly A, Samuel D.
Impact of negative air pressure in ICU rooms on the risk of
pulmonary aspergillosis in COVID-19 patients. Crit Care.
2020;24(1):538-544.
17. Cimolai N. The Complexity of Co-Infections in the Era of
COVID-19. SN Compr Clin Med. 2021;1-13.
18. Patanavanich R, Glantz SA. Smoking Is Associated With
COVID-19 Progression: A Meta-analysis. Nicotine Tob Res.
2020;22(9):1653-1656.
19. Pittet LA, Hall-Stoodley L, Rutkowski MR, Harmsen AG.
Influenza virus infection decreases tracheal mucociliary velocity
and clearance of Streptococcus pneumoniae. Am J Respir Cell
Mol Biol. 2010;42(4):450-460.
20. Kothari A, Singh V, Nath UK, et al. Immune dysfunction and
multiple treatment modalities for the SARS-CoV-2 pandemic:
races of uncontrolled running sweat? Biol (Basel).
2020;9(9):243-254.
21. Magira EE, Jiang Y, Economides M, Tarrand J, Kontoyiannis
DP. Mixed mold pulmonary infections in haematological cancer
patients in a tertiary care cancer centre. Mycoses.
2018;61(11):861-867.
22. Chakrabarti A, Kaur H, Savio J, et al. Epidemiology and clinical
outcomes of invasive mould infections in Indian intensive care
units (FISF study). J Crit Care. 2019;51:64-70.
23. Mohan V. Why are Indians more prone to diabetes?. J Assoc
Physicians India. 2004;52:468-474.
24. Huda MSB, Shaho S, Trivedi B, et al. Diabetic emergencies
during the COVID-19 pandemic: A case-control study. Diabet
Med. 2021;38(1):e14416.
25. Wang S, Ma P, Zhang S, et al. Fasting blood glucose at
admission is an independent predictor for 28-day mortality in
patients with COVID-19 without previous diagnosis of diabetes:
a multi-centre retrospective study. Diabetologia. 2020;
63(10):2102-2111.
26. Thompson Iii GR, Cornely OA, Pappas PG, et al. Invasive
Aspergillosis as an Under-recognized Superinfection in COVID-
19. Open Forum Infect Dis. 2020;7(7):ofaa242.
27. Banerjee M, Pal R, Bhadada SK. Intercepting the deadly trinity
of mucormycosis, diabetes and COVID-19 in India. Postgrad
Med J. 2021;2021:140537.
28. Rammaert B, Lanternier F, Zahar JR, et al. Healthcareassociated mucormycosis. Clin Infect Dis. 2012;54(1):S44-S54.
29. Guegan H, Iriart X, Bougnoux ME, Berry A, Robert-Gangneux
F, Gangneux JP. Evaluation of MucorGenius® mucorales PCR
assay for the diagnosis of pulmonary mucormycosis. J Infect.
2020;81(2):311-317.
30. Patel A, Agarwal R, Rudramurthy SM, et al. Multicenter
epidemiologic study of coronavirus disease-associated
mucormycosis, India. Emerg Infect Dis. 2021;27(9):2349