Immunological response to COVID-19 and its role as a predisposing factor in invasive aspergillosis

Document Type : Reviews


1 Invasive Fungi Center, Communicable Diseases Research Institute, Mazandaran University of Medical Sciences, Sari, Iran

2 Department of Medical Parasitology and Mycology, School of Medicine, Babol University of Medical Sciences, Babol, Iran

3 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

4 Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria

5 Division of Infectious Diseases and Global Health, University of California San Diego, La Jolla, California



The world is involved with a pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2. The clinical manifestations of reported COVID-19-associated pulmonary impairments range from asymptomatic infections to a pneumonia-induced acute respiratory distress syndrome that requires mechanical ventilation. Fungal superinfections complicating the clinical course remain underexplored. Angiotensin-converting enzyme 2, the receptor for COVID-19 that is mainly expressed in airway epithelia and lung parenchyma, is considered an important regulator of innate immunity. With regard to the viral-cell interaction, imbalanced immune regulation between protective and altered responses caused by the exacerbation of inflammatory responses should be considered a major contributor to secondary pulmonary aspergillosis. In addition, the complex inherited factors, age-related changes, and lifestyle may also affect immune responses. The complication and persistence of invasive aspergillosis have been well described in patients with severe influenza or COVID-19. However, there is a scarcity of information about the immunological mechanisms predisposing patients with COVID-19 to fungal co-infections. Therefore, this study was conducted to investigate the aforementioned domain.


1. Kui L, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J. 2020; 133(9):1025-31.
2. Verweij PE, Gangneux JP, Bassetti M, Brüggemann RJ, Cornely OA, Koehler P, et al. Diagnosing COVID-19-associated pulmonary aspergillosis. Lancet Microbe. 2020; 1(2):e53-5.
3. Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012; 487(7408):477-81.
4. Hernández PP, Mahlakõiv T, Yang I, Schwierzeck V, Nguyen N, Guendel F, et al. Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection, Nature Immunology volume. Nat Immunol. 2015; 16(7):698-707.
5. Cunha C, Carvalho A, Esposito A, Bistoni F, Romani L. DAMP signaling in fungal infections and diseases. Front Immunol. 2012; 3:286.
6. Arastehfar A, Carvalho A, van de Veerdonk FL, Jenks JD, Koehler P, Krause R, et al. COVID-19 associated pulmonary aspergillosis (CAPA)-From immunology to treatment. J Fungi. 2020; 6(2):91.
7. Mohamed A, Hassan T, Trzos-Grzybowska M, Thomas J, Quinn A, O'Sullivan M, et al. Multi-triazole-resistant Aspergillus fumigatus and SARS-CoV-2 co-infection: a lethal combination. Med Mycol Case Rep. 2020; In Press.
8. Meijer EF, Dofferhoff AS, Hoiting O, Buil JB, Meis JF. Azole-resistant COVID-19-associated pulmonary Aspergillosis in an immunocompetent host: a case report. J Fungi. 2020; 6(2):79.
9. Zheng M, Zhao X, Zheng S, Chen D, Pengcheng Du, Xinglin Li, et al. Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion. Emerg Microbes Infect. 2020; 9(1):1567-79.
10. Schloer S, Goretzko J, Kühnl A, Brunotte L, Ludwig S, Reschera U. The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo. Emerg Microbes Infect. 2019; 8(1):80-93.
11. Davy CM, Donaldson ME, Subudhi S, Rapin N, Warnecke L, Turner JM, et al. White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats. Sci Rep. 2018; 8(1):15508.
12. Dickson RP, Martinez FJ, Huffnagle GB. The role of the microbiome in exacerbations of chronic lung diseases. Lancet. 2014; 384(9944):691-702.
13. Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019; 23(1):99.
14. Krüger W, Vielreicher S, Kapitan M, Jacobsen ID, Niemiec MJ. Fungal-bacterial interactions in health and disease. Pathogens. 2019; 8(2):70.
15. Andreakos E, Salagianni M, Galani IE, Koltsida O. Interferon-λs: front-line guardians of immunity and homeostasis in the respiratory tract. Front Immunol. 2017; 8:1232.
16. Wang H, Ding Y, Li X, Yang L, Zhang W, Kang W. Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. N Engl J Med. 2003; 349(5):507-8.
17. Sales-Campos H, Tonani L, Cardoso CR, Kress MR. The immune interplay between the host and the pathogen in Aspergillus fumigatus lung infection. Biomed Res Int. 2013; 2013:693023.
Tavakoli M et al. Immunological response to COVID-19 and invasive aspergillosis
Curr Med Mycol, 2020, 6(4): 75-79 79
18. Richard N, Marti L, Varrot A, Guillot L, Guitard J, Hennequin C, et al. Human bronchial epithelial cells inhibit Aspergillus fumigatus germination of extracellular conidia via FleA recognition. Sci Rep. 2018; 8(1):15699.
19. Wang X, Hu J, Price SR. Inhibition of PI3-kinase signaling by glucocorticoids results in increased branched-chain amino acid degradation in renal epithelial cells. Am J Physiol Cell Physiol. 2007; 292(5):C1874-9.
20. Loeffler J, Haddad Z, Bonin M, Romeike N, Mezger M, Schumacher U, et al. Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus. J Med Microbiol. 2009; 58(Pt 1):49-58.
21. Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, et
al. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N Engl J Med. 2014; 370(5):421-32.
22. Bahadoran A, Lee SH, Wang SM, Manikam R, Rajarajeswaran J, Raju CS, et al. Immune responses to influenza virus and its correlation to age and inherited factors. Front Microbiol. 2016; 7:1841.
23. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020; 10(2):102-8.
24. Chauhan B, Santiago L, Kirschmann DA, Hauptfeld V, Knutsen AP, Hutcheson PS, et al. The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary
Volume 6, Issue 4
December 2020
Pages 75-79
  • Receive Date: 28 August 2020
  • Revise Date: 24 October 2020
  • Accept Date: 07 November 2020
  • First Publish Date: 22 November 2020