Preview

Kuban Scientific Medical Bulletin

Advanced search

Rhinocerebral Form of Invasive Mycosis in COVID-19 Patients: Clinical Course, Diagnosis, Treatment Experience

https://doi.org/10.25207/1608-6228-2022-29-5-63-79

Abstract

Background. The incidence of invasive mycoses is reported to increase among patients with a history of new coronavirus infection COVID-19. Adhesion and damage of endothelial cells by zygomycetes lead to fungus angioinvasion, release of a large number of fungal proteases, lipases and mycotoxins, as well as vascular thrombosis, subsequent necrosis of tissues.

Objectives. Improvement of the diagnosis and treatment for COVID-19 associated invasive mycosis.

Methods. Examination and treatment of 143 patients with invasive mycosis of the maxillofacial area in the period from August 2021 to May 2022 at the Maxillofacial Unit of Regional Clinical Hospital of Emergency Medical Care, Krasnodar Krai, Russia. The diagnosis was confi rmed by cytological, culture-based methods, as well as pathomorphological study of surgical specimen. Follow-up monitoring was carried out in 1, 3, 6 months, with repeated CT and MRI investigations. The group under follow-up monitoring included 91 patients. The incidence of signs was determined via descriptive statistics methods in proportion of the total number of observations and expressed as a percentage. Statistika 12.5 and Excel 2010 (Windows 10) were used in the study, the graphical representation of the material was made in the same programs.

Results. Manifestation of invasive mycoses of the maxillofacial area occurred during the early convalescent period of coronavirus infection in specialized infectious hospitals or within two weeks after discharge from the hospital. A typical clinical picture includes rhinocerebral zygomycosis with the development of fungal osteomyelitis of the upper jaw, nasal bones, zygomatic bone, ethmoidal labyrinth bones, sphenoid bone, frontal bone. 17 cases (11.9%) had a lethal outcome as a result of disseminated form of fungal infection caused by Mucorales (14 patients), Aspergillus (3 patients) with damage to the brain, lungs, kidneys and fatal massive necrotic lesions of the craniofacial area. An integrated approach embraced early antifungal therapy (Amphotericin B) as well as surgical debridement of the lesions and provided a positive effect in treatment.

Conclusion. Invasive fungal infections require prompt diagnosis and early prescription of antifungal therapy (prior to histological confi rmation of diagnosis) to minimize consequences and prevent fatal outcome. Due to the nonspecifi c nature of clinical symptoms and diffi culties of early diagnosis of invasive zygomycosis and aspergillosis, it is necessary to be alert to potential invasive aggressive mycoses in immunocompromised patients who have a history of a new coronavirus infection COVID-19.

About the Authors

Yu. V. Savosin
Kuban State Medical University

Yuriy V. Savosin — Senior Laboratory Assistant, Department of Surgical Dentistry and Maxillofacial Surgery;  Senior Resident, Department of Maxillofacial Surgery Clinical Emergency Medical Care Hospital

Mitrofanа Sedina str., 4, Krasnodar, 350063



S. K. Shafranova
Kuban State Medical University

Svetlana K. Shafranova — Candidate of Medical Science, Associate Professor, Department of Surgical Dentistry and Maxillofacial Surgery 

Mitrofanа Sedina str., 4, Krasnodar, 350063



T. V. Gaivoronskaya
Kuban State Medical University

Tatyana V. Gaivoronskaya — M.D, Prof.; Vice Rector for Education and Training, Head of the Department of Surgical Dentistry and Maxillofacial Surgery

Mitrofanа Sedina str., 4, Krasnodar, 350063



M. G. Avdeeva
Kuban State Medical University

Marina G. Avdeeva — M.D., Prof; Head of the Department of Infectious Diseases and Phthisiopulmonology 

Mitrofanа Sedina str., 4, Krasnodar, 350063



S. A. Vartanyan
Regional Clinical Hospital of Emergency Medical Care; Kuban State Medical University
Russian Federation

Seyran A. Vartanyan — Head of Maxillofacial Surgery Unit of Clinical Emergency Medical Care Hospital ; Chief Visiting Maxillofacial Surgeon of Krasnodar Krai; Research Assistant of ICPE, Surgery Department #2 

40 let Pobedy str., 14, Krasnodar, 350042



References

1. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J. Infect. 2020; 81(2): 266–275. DOI: 10.1016/j.jinf.2020.05.046

2. Langford B.J., So M., Raybardhan S., Leung V., Westwood D., MacFadden D.R., Soucy J.R., Daneman N. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin. Microbiol. Infect. 2020; 26(12): 1622–1629. DOI: 10.1016/j.cmi.2020.07.016

3. Chen X., Liao B., Cheng L., Peng X., Xu X., Li Y., Hu T., Li J., Zhou X., Ren B. The microbial coinfection in COVID-19. Appl. Microbiol. Biotechnol. 2020; 104(18): 7777–7785. DOI: 10.1007/s00253-020-10814-6

4. Avdeeva M.G., Kulbuzheva M.I., Zotov S.V., Zhuravleva Ye.V., Yatsukova A.V. Microbial landscape in hospital patients with new coronavirus disease (COVID-19), antibiotic resistance comparison vs. Pre-covid stage: a prospective study. Kuban Scientific Medical Bulletin. 2021; 28(5):14–28 (In Russ., English abstract). DOI: 10.25207/1608-6228-2021-28-5-14-28

5. Peng J., Wang Q., Mei H., Zheng H., Liang G., She X., Liu W. Fungal co-infection in COVID-19 patients: evidence from a systematic review and meta-analysis. Aging (Albany NY). 2021; 13(6): 7745–7757. DOI: 10.18632/aging.202742

6. Mohamed A., Rogers T.R., Talento A.F. COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges. J. Fungi (Basel). 2020; 6(3): 115. DOI: 10.3390/jof6030115

7. Machado M., Valerio M., Álvarez-Uria A., Olmedo M., Veintimilla C., Padilla B., De la Villa S., Guinea J., Escribano P., Ruiz-Serrano M.J., Reigadas E., Alonso R., Guerrero J.E., Hortal J., Bouza E., Muñoz P.; COVID-19 Study Group. Invasive pulmonary aspergillosis in the COVID-19 era: An expected new entity. Mycoses. 2021; 64(2): 132–143. DOI: 10.1111/myc.13213

8. Song G., Liang G., Liu W. Fungal Co-infections Associated with Global COVID-19 Pandemic: A Clinical and Diagnostic Perspective from China. Mycopathologia. 2020; 185(4): 599–606. DOI: 10.1007/s11046-020-00462-9

9. Heaney A.K., Head J.R., Broen K., Click K., Taylor J., Balmes J.R., Zelner J., Remais J.V. Coccidioidomycosis and COVID-19 Co-Infection, United States, 2020. Emerg. Infect. Dis. 2021; 27(5): 1266–1273. DOI: 10.3201/eid2705.204661

10. Muthu V., Rudramurthy S.M., Chakrabarti A., Agarwal R. Epidemiology and Pathophysiology of COVID-19-Associated Mucormycosis: India Versus the Rest of the World. Mycopathologia. 2021; 186(6): 739–754. DOI: 10.1007/s11046-021-00584-8

11. Tabassum T., Araf Y., Moin A.T., Rahaman T.I., Hosen M.J. COVID-19-associated-mucormycosis: possible role of free iron uptake and immunosuppression. Mol. Biol. Rep. 2022; 49(1): 747–754. DOI: 10.1007/s11033-021-06862-4

12. Sundaram N., Bhende T., Yashwant R., Jadhav S., Jain A. Mucormycosis in COVID-19 patients. Indian J. Ophthalmol. 2021; 69(12): 3728–3733. DOI: 10.4103/ijo.IJO_1316_21

13. Chao C.M., Lai C.C., Yu W.L. COVID-19 associated mucormycosis — An emerging threat. J. Microbiol. Immunol. Infect. 2022; 55(2): 183–190. DOI: 10.1016/j.jmii.2021.12.007

14. Khostelidi S.N., Zaytsev V.A., Vartanyan S.A., Nikitin N.A., Evtukh G.N., Gilalov M.N., Portnov G.V., Zubareva A.A., Baranova I.B., Bogomolova T.S., Avdeenko Yu.L., Shadrivova O.V., Desyatik E.A., Shagdileeva E.V., Borzova Yu.V., Krivolapov Yu.A., Vasilyeva N.V., Klimko N.N. cormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study. Journal Infectology. 2022; 14(2): 116-127 (In Russ. English abstract). DOI: 10.22625/2072-6732-2022-14-2-116-127

15. Singh K., Kumar S., Shastri S., Sudershan A., Mansotra V. Black fungus immunosuppressive epidemic with Covid-19 associated mucormycosis (zygomycosis): a clinical and diagnostic perspective from India. Immunogenetics. 2022; 74(2): 197–206. DOI: 10.1007/s00251-021-01226-5

16. Didehdar M., Chegini Z., Moradabadi A., Anoushirvani A.A., Tabaeian S.P., Yousefimashouf M., Shariati A. Gastrointestinal mucormycosis: A periodic systematic review of case reports from 2015 to 2021. Microb. Pathog. 2022; 163: 105388. DOI: 10.1016/j.micpath.2022.105388

17. Bhattacharyya A., Sarma P., Kaur H., Kumar S., Bhattacharyya J., Prajapat M., Prakash A., Sharma S., Reddy D.H., Thota P., Bansal S., Gautam B.S., Medhi B. COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis. Indian J. Pharmacol. 2021; 53(6): 499–510. DOI: 10.4103/ijp.ijp_839_21

18. Sanghvi D., Kale H. Imaging of COVID-19-associated craniofacial mucormycosis: a black and white review of the “black fungus”. Clin. Radiol. 2021; 76(11): 812–819. DOI: 10.1016/j.crad.2021.07.004

19. Al-Tawfiq J.A., Alhumaid S., Alshukairi A.N., Temsah M.H., Barry M., Al Mutair A., Rabaan A.A., Al-Omari A., Tirupathi R., Al Qahtani M., Al Bahrani S., Dhama K. COVID-19 and mucormycosis superinfection: the perfect storm. Infection. 2021; 49(5): 833–853. DOI: 10.1007/s15010-021-01670-1

20. Mahalaxmi I., Jayaramayya K., Venkatesan D., Subramaniam M.D., Renu K., Vijayakumar P., Narayanasamy A., Gopalakrishnan A.V., Kumar N.S., Sivaprakash P., Sambasiva Rao K.R.S., Vellingiri B. Mucormycosis: An opportunistic pathogen during COVID-19. Environ. Res. 2021; 201: 111643. DOI: 10.1016/j.envres.2021.111643

21. Manchanda S., Semalti K., Bhalla A.S., Thakar A., Sikka K., Verma H. Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review. Emerg. Radiol. 2021; 28(6): 1063–1072. DOI: 10.1007/s10140-021-01980-9

22. Ullmann A.J., Aguado J.M., Arikan-Akdagli S., Denning D.W., Groll A.H., Lagrou K., Lass-Flörl C., Lewis R.E., Munoz P., Verweij P.E., Warris A., Ader F., Akova M., Arendrup M.C., Barnes R.A., Beigelman-Aubry C., Blot S., Bouza E., Bruggemann R.J.M., Buchheidt D., Cadranel J., Castagnola E., Chakrabarti A., Cuenca-Estrella M., Dimopoulos G., Fortun J., Gangneux J.P., Garbino J., Heinz W.J., Herbrecht R., Heussel C.P., Kibbler C.C., Klimko N., Kullberg B.J., Lange C., Lehrnbecher T., Löffler J., Lortholary O., Maertens J., Marchetti O., Meis J.F., Pagano L., Ribaud P., Richardson M., Roilides E., Ruhnke M., Sanguinetti M., Sheppard D.C., Sinkó J., Skiada A., Vehreschild M.J.G.T., Viscoli C., Cornely O.A. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin. Microbiol. Infect. 2018; 24 Suppl 1: e1–e38. DOI: 10.1016/j.cmi.2018.01.002

23. Avdeeva M.G., Mozgaleva N.V., Parkhomenko Y.G. Malignant course of invasive pulmonary aspergillosis in the new coronavirus infection COVID-19. Epidemiology and Infectious Diseases. 2021; 26(2): 84–91 (In Russ., English abstract). DOI: 10.17816/EID105289

24. Ledoux M.P., Guffroy B., Nivoix Y., Simand C., Herbrecht R. Invasive Pulmonary Aspergillosis. Semin. Respir. Crit. Care Med. 2020; 41(1): 80–98. DOI: 10.1055/s-0039-3401990

25. Garg D., Muthu V., Sehgal I.S., Ramachandran R., Kaur H., Bhalla A., Puri G.D., Chakrabarti A., Agarwal R. Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature. Mycopathologia. 2021; 186(2): 289–298. DOI: 10.1007/s11046-021-00528-2

26. Wiederhold N.P. Emerging Fungal Infections: New Species, New Names, and Antifungal Resistance. Clin. Chem. 2021; 68(1): 83–90. DOI: 10.1093/clinchem/hvab217

27. Brackin A.P., Hemmings S.J., Fisher M.C., Rhodes J. Fungal Genomics in Respiratory Medicine: What, How and When? Mycopathologia. 2021; 186(5): 589–608. DOI: 10.1007/s11046-021-00573-x

28. Taraskina A.E., Pchelin I.M., Ignatieva S.M., Spiridonova V.A., Uchevatkina A.E., Filippova L.V., Frolova E.V., Vasilyeva N.V. Molecular genetic methods for detection and species identification of fungal order mucorales in accordance with the global guideline for the diagnosis and management of mucormycosis (literature review). Problemy Meditsinskoi Mikologii. 2020; 22(1): 3–14 (In Russ., English abstract). DOI: 10.24412/1999-6780-2020-1-3-14

29. Lai C.C., Yu W.L. COVID-19 associated with pulmonary aspergillosis: A literature review. J. Microbiol. Immunol. Infect. 2021; 54(1): 46–53. DOI: 10.1016/j.jmii.2020.09.004

30. Al-Hatmi A.M.S., Mohsin J., Al-Huraizi A., Khamis F. COVID-19 associated invasive candidiasis. J. Infect. 2021; 82(2): e45–e46. DOI: 10.1016/j.jinf.2020.08.005

31. Posteraro B., Torelli R., Vella A., Leone P.M., De Angelis G., De Carolis E., Ventura G., Sanguinetti M., Fantoni M. Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report. J .Fungi (Basel). 2020; 6(3): 163. DOI: 10.3390/jof6030163

32. Chowdhary A., Tarai B., Singh A., Sharma A.. Multidrug-Resistant Candida auris Infections in Critically Ill Coronavirus Disease Patients, India, April-July 2020. Emerg. Infect. Dis. 2020; 26(11): 2694–2696. DOI: 10.3201/eid2611.203504.

33. Hussain S., Baxi H., Riad A., Klugarová J., Pokorná A., Slezáková S., Líčenik R., Najmi A.K., Klugar M. COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping. Int. J. Environ. Res. Public. Health. 2021; 18(19): 10340. DOI: 10.3390/ijerph181910340


Review

For citations:


Savosin Yu.V., Shafranova S.K., Gaivoronskaya T.V., Avdeeva M.G., Vartanyan S.A. Rhinocerebral Form of Invasive Mycosis in COVID-19 Patients: Clinical Course, Diagnosis, Treatment Experience. Kuban Scientific Medical Bulletin. 2022;29(5):63-79. (In Russ.) https://doi.org/10.25207/1608-6228-2022-29-5-63-79

Views: 413


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1608-6228 (Print)
ISSN 2541-9544 (Online)