Review Article

A Comprehensive Study of the Global COVID-19 Pandemic and Fungal Co-Infections: A Review

Abstract

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-19), which has resulted in high death tolls around the world and a significant health burden. The purpose of this study is to bring attention to the early diagnosis and treatment of fungal diseases in coronavirus disease 2019 (COVID-19) patients. Materials and Methods: We searched peer-reviewed articles, reviews, surveillance reports, and clinical studies published from January 2020 to December 2023 using databases including PubMed, Scopus, and Web of Science. Results: Severely ill COVID-19 patients are at high risk for life-threatening fungal co-infections. The most prevalent is pulmonary aspergillosis, affecting up to a third of ICU patients, largely driven by corticosteroid use. Candidiasis is also common with prolonged ICU stays. Diagnosis is challenging, and treatment requires specific antifungals. Conclusion: Fungal co-infections increase COVID-19 mortality. Manage with early diagnosis, targeted antifungals, and risk factor control. Global focus on awareness, diagnostics, and antifungal stewardship is crucial. Keywords: Covid-19; Sars-cov-2; Fungal co-infection; Aspergillosis; Mucormycosis; Candidiasis.
1. Pan A, Liu L, Wang C, Guo H, Hao X, Wang Q, et al. Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan, China. Jama. 2020;323(19):1915-23.
2. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet. 2020;395(10229):1033-4.
3. Rawson TM, Moore LS, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clinical infectious diseases. 2020;71(9):2459-68.
4. Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. Jama. 2020;323(20):2085-6.
5. Fekkar A, Lampros A, Mayaux J, Poignon C, Demeret S, Constantin J-M, et al. Occurrence of invasive pulmonary fungal infections in patients with severe COVID-19 admitted to the ICU. American journal of respiratory and critical care medicine. 2021;203(3):307-17.
6. Arastehfar A, Carvalho A, Houbraken J, Lombardi L, Garcia-Rubio R, Jenks J, et al. Aspergillus fumigatus and aspergillosis: From basics to clinics. Studies in Mycology. 2021;100(1):100115-.
7. Amin A, Vartanian A, Poladian N, Voloshko A, Yegiazaryan A, Al-Kassir AL, et al. Root causes of fungal coinfections in COVID-19 infected patients. Infectious Disease Reports. 2021;13(4):1018-35.
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.
9. Prattes J, Koehler P, Hoenigl M. COVID-19 associated pulmonary aspergillosis: regional variation in incidence and diagnostic challenges. Intensive care medicine. 2021;47(11):1339-40.
10. Alanio A, Dellière S, Fodil S, Bretagne S, Mégarbane B. Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19. The Lancet Respiratory Medicine. 2020;8(6):e48-e9.
11. Prattes J, Wauters J, Giacobbe DR, Salmanton-García J, Maertens J, Bourgeois M, et al. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology. Clinical Microbiology and Infection. 2022;28(4):580-7.
12. Hashim Z, Nath A, Khan A, Neyaz Z, Marak RS, Areekkara P, et al. New insights into development and mortality of COVID‐19‐associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients. Mycoses. 2022;65(11):1010-23.
13. White PL, Dhillon R, Cordey A, Hughes H, Faggian F, Soni S, et al. A national strategy to diagnose coronavirus disease 2019–associated invasive fungal disease in the intensive care unit. Clinical Infectious Diseases. 2021;73(7):e1634-e44.
14. Tappe B, Lauruschkat CD, Strobel L, Pantaleón García J, Kurzai O, Rebhan S, et al. COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds. medRxiv. 2022:2022.04. 21.22274082.
15. Nitipong Permpalung M, Chiang TP-Y, Massie AB. COVID-19 Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients. Clin Infect Dis. 2021;74:83-91.
16. Egger M, Bussini L, Hoenigl M, Bartoletti M. Prevalence of COVID-19-Associated Pulmonary Aspergillosis: Critical Review and Conclusions. Journal of Fungi. 2022;8(4):390.
17. Kariyawasam RM, Dingle TC, Kula BE, Vandermeer B, Sligl WI, Schwartz IS. Defining COVID-19 associated pulmonary aspergillosis: systematic review and meta-analysis. Clinical Microbiology and Infection. 2022.
18. Kim J-Y, Kang C-I, Lee JH, Lee WJ, Huh K, Cho SY, et al. Clinical features and outcomes of invasive fusariosis: a case series in a single center with literature review. Infection & Chemotherapy. 2021;53.
19. Koehler P, Bassetti M, Chakrabarti A, Chen SC, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. The Lancet Infectious Diseases. 2021;21(6):e149-e62.
20. O'Shea M, Birkhamshaw E, Khalil R, Wickramasinghe N, Hamad M, Crooks N, et al. Implementation of a diagnostic algorithm for COVID-19-associated pulmonary aspergillosis. Journal of Hospital Infection. 2022;129:203-6.
21. Pasquier G, Bounhiol A, Robert Gangneux F, Zahar JR, Gangneux JP, Novara A, et al. A review of significance of Aspergillus detection in airways of ICU COVID‐19 patients. Mycoses. 2021;64(9):980-8.
22. Serris A, Danion F, Lanternier F. Disease entities in mucormycosis. J Fungi 5 (1): 23. Link: https://bit ly/3rH0DB1. 2019.
23. Hussain S, Riad A, Singh A, Klugarová J, Antony B, Banna H, et al. Global prevalence of COVID-19-associated mucormycosis (CAM): living systematic review and meta-analysis. Journal of Fungi. 2021;7(11):985.
24. Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2021;15(4):102146.
25. Sugar AM. Mucormycosis. Clinical infectious diseases. 1992;14(Supplement_1):S126-S9.
26. Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SC, 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. The Lancet infectious diseases. 2019;19(12):e405-e21.
27. Honavar SG. Code mucor: guidelines for the diagnosis, staging and management of rhino-orbito-cerebral mucormycosis in the setting of COVID-19. Indian journal of ophthalmology. 2021;69(6):1361.
28. Chegini Z, Didehdar M, Khoshbayan A, Rajaeih S, Salehi M, Shariati A. Epidemiology, clinical features, diagnosis and treatment of cerebral mucormycosis in diabetic patients: a systematic review of case reports and case series. Mycoses. 2020;63(12):1264-82.
29. Rabiei MM, Zali A, Roodsari SR, Arab-Mazar Z, Lotfali E. Fungal Central Nervous System Infections in Patients With COVID-19. International Clinical Neuroscience Journal. 2021;8(4):154-6.
30. Smith C, Lee SC. Current treatments against mucormycosis and future directions. PLoS Pathogens. 2022;18(10):e1010858.
31. Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diagnosis of mucormycosis: an update. Journal of fungi. 2020;6(4):265.
32. Beiglboeck FM, Theofilou NE, Fuchs MD, Wiesli MG, Leiggener C, Igelbrink S, et al. Managing mucormycosis in diabetic patients: A case report with critical review of the literature. Oral Diseases. 2022;28(3):568-76.
33. Niemiec MJ, Kapitan M, Polke M, Jacobsen ID. Commensal to pathogen transition of Candida albicans. 2017.
34. Ahmed N, Mahmood MS, Ullah MA, Araf Y, Rahaman TI, Moin AT, et al. COVID-19-associated candidiasis: possible patho-mechanism, predisposing factors, and prevention strategies. Current Microbiology. 2022;79(5):127.
35. Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M, et al. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clinical Microbiology and Infection. 2021;27(1):83-8.
36. Nieto M, Robles JC, Causse M, Gutiérrez L, Cruz Perez M, Ferrer R, et al. Polymerase chain reaction versus blood culture to detect Candida species in high-risk patients with suspected invasive Candidiasis: The MICAFEM Study. Infectious Diseases and Therapy. 2019;8:429-44.
37. Clancy CJ, Nguyen MH. Diagnosing invasive candidiasis. Journal of clinical microbiology. 2018;56(5):e01909-17.
38. Gonzalez-Lara MF, Ostrosky-Zeichner L, editors. Invasive candidiasis. Seminars in Respiratory and Critical Care Medicine; 2020: Thieme Medical Publishers.
39. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2016;62(4):e1-e50.
40. Drogari-Apiranthitou M, Mpakosi A, Siopi M, Argyropoulou A, Vrioni G, Mamali V, et al. P185 Epidemiology of human fusariosis in Greece: results from a 16-year nationwide multicenter survey. Medical Mycology. 2022;60(Supplement_1):myac072P185.
41. Damani J. COVID-19-ASSOCIATED PULMONARY FUSARIUM INFECTION IN A NON-CRITICALLY ILL IMMUNOCOMPETANT PATIENT. Chest. 2021;160(4):A286.
42. Herkert PF, Al-Hatmi AM, de Oliveira Salvador GL, Muro MD, Pinheiro RL, Nucci M, et al. Molecular characterization and antifungal susceptibility of clinical Fusarium species from Brazil. Frontiers in Microbiology. 2019;10:737.
43. Szydłowicz M, Matos O. Pneumocystis pneumonia in the COVID-19 pandemic era: similarities and challenges. Trends in parasitology. 2021;37(10):859-62.
44. Gioia F, Albasata H, Hosseini-Moghaddam SM. Concurrent infection with SARS-CoV-2 and pneumocystis jirovecii in immunocompromised and immunocompetent individuals. Journal of Fungi. 2022;8(6):585.
45. Chong WH, Saha BK, Chopra A. Narrative review of the relationship between COVID-19 and PJP: does it represent coinfection or colonization? Infection. 2021;49(6):1079-90.
46. Menon AA, Berg DD, Gay EB, Fredenburgh LE. Reply to Blaize et al.: COVID–19–related respiratory failure and lymphopenia do not seem associated with pneumocystosis. American Journal of Respiratory and Critical Care Medicine. 2020;202(12):1736-7.
47. Weyant RB, Kabbani D, Doucette K, Lau C, Cervera C. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opinion on Pharmacotherapy. 2021;22(12):1579-92.
48. Keshmiri MS, Aghdasi S, Noorali S, Shafaghi S, Serati A, Naghashzadeh F, Movahed MR, Shadanfar S, Hajimoradi M, Kashani BS. Bronchial Artery Embolization for Life-Threatening Hemoptysis in COVID-19 Patients. Int J Angiol. 2022 May 19;33(4):307-314. doi: 10.1055/s-0042-1745839. PMID: 39502345; PMCID: PMC11534474.
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Keywords
Covid-19; Sars-cov-2; Fungal co-infection; Aspergillosis; Mucormycosis; Candidiasis.

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Bahrami N, Bayat M, Surani Z, Shirian S, Shahverdi M, Karimi R, Tabatabaee SN, Abolfathi A, Yousefi-Koma H, Shafaghi S, Ahmadinia M, Mohamadnia A. A Comprehensive Study of the Global COVID-19 Pandemic and Fungal Co-Infections: A Review. J Craniomaxillofac Res. 2025;12(3):148-155.