Ellie Rose Mattoon¹, Radames JB Cordero² and Arturo Casadevall^2
1Krieger School of Arts and Sciences, Johns Hopkins University Baltimore, Maryland, USA
²Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, North Wolfe Street, Baltimore, USA

Part of the book: The Book of Fungal Pathogens 

Abstract

The physiological factors of COVID-19 infection and the environmental factors of treatment have predisposed a larger patient population to fungal infections. In this review, we provide an overview of the three most frequently documented fungal infections associated with COVID-19: aspergillosis, mucormycosis, and candidemia. For all three secondary infections, we review the literature making efforts to determine the incidence of infection, physiological or environmental causes of co-infection with COVID-19, and the mortality of infection both with and without COVID-19. These infections vary in their etiology in association with COVID-19 infection, in addition to their recommended treatments and mortality. Ultimately, we demonstrate the importance of early diagnosis of secondary infections and the proper identification of fungal pathogens for treatment purposes, while also highlighting research gaps in this new field.

Keywords: COVID-19, secondary fungal infections, COVID-19 associated pulmonary
aspergillosis (CAPA), COVID-19 associated mucormycosis (CAM), COVID-19 associated candidemia (CAC)

References

[1] WHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus (COVID-19) Dashboard with
Vaccination Data [Internet]. [cited 2022 Mar 13]. Available from: https://covid19.who.int/.
[2] Bösmüller, H., Matter, M., Fend, F., and Tzankov, A. (2021).
The pulmonary pathology of COVID 19. Virchows Arch., Jan, 478(1), 137–150.
[3] Morgulchik, N., Athanasopoulou, F., Chu, E., Lam, Y., and Kamaly, N. (2022). Potential therapeutic
approaches for targeted inhibition of inflammatory cytokines following COVID-19 infection-induced
cytokine storm. Interface Focus., Feb 6, 12(1), 20210006.
[4] Delavari, S., Abolhassani, H., Abolnezhadian, F., Babaha, F., Iranparast, S., Ahanchian, H., et al.
(2021). Impact of SARS-CoV-2 Pandemic on Patients with Primary
Immunodeficiency. J Clin Immunol., Feb, 41(2), 345–355.
[5] Tsiodras, S., Samonis, G., Boumpas, D. T., and Kontoyiannis, D. P. (2008). Fungal infections
complicating tumor necrosis factor alpha blockade therapy. Mayo Clin Proc., Feb, 83(2), 181–194.
[6] Casadevall, A. (2018). Fungal diseases in the 21st century: the near and far horizons.
Pathog Immun., Sep 25, 3(2), 183–196.
[7] Vallabhaneni, S., Mody, R. K., Walker, T., and Chiller, T. (2016). The global burden of fungal diseases.
Infect Dis Clin North Am., Mar, 30(1), 1–11.
[8] Noreen, S., Maqbool, I., and Madni, A. (2021). Dexamethasone: Therapeutic potential, risks, and future
projection during COVID-19 pandemic. Eur J Pharmacol., Mar 5, 894, 173854.
[9] Giacobbe, D. R., Battaglini, D., Ball, L., Brunetti, I., Bruzzone, B., Codda, G., et al. (2020).
Bloodstream infections in critically ill patients with COVID-19.
Eur J Clin Invest., Oct, 50(10), e13319.
[10] Rawson, T. M., Moore, L. S. P., Zhu, N., Ranganathan, N., Skolimowska, K., Gilchrist, M., et al.
(2020). Bacterial and Fungal Coinfection in Individuals with Coronavirus: A Rapid Review to Support
COVID-19 Antimicrobial Prescribing. Clin Infect Dis., 2020 Dec 3, 71(9), 2459–2468.
[11] Srinivasan, A. Antibiotic Resistance (AR), Antibiotic Use (AU), and COVID-19. HHS, Feb 2021.
[12] Rawson, T. M., Moore, L. S. P., Castro-Sanchez, E., Charani, E., Davies, F., Satta, G., et al. (2020).
COVID-19 and the potential long-term impact on antimicrobial resistance. J Antimicrob Chemother.,
Jul 1, 75(7), 1681–1684.
[13] Spees, A. M., Wangdi, T., Lopez, C. A., Kingsbury, D. D., Xavier, M. N., Winter, S. E., et al. (2013).
Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate
respiration. MBio., Jul 2, 4(4).
[14] Mayer, B. T., Srinivasan, S., Fiedler, T. L., Marrazzo, J. M., Fredricks, D. N., and Schiffer, J. T. (2015).
Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial
vaginosis. J Infect Dis., Sep 1, 212(5), 793–802.
[15] Casalini, G., Giacomelli, A., Ridolfo, A., Gervasoni, C., and Antinori, S. (2021). Invasive Fungal
Infections Complicating COVID-19: A Narrative Review. J Fungi (Basel)., Oct 29, 7(11).
[16] Baddley, J. W., and Forrest, G. N. (2019). AST Infectious Diseases Community of Practice.
Cryptococcosis in solid organ transplantation-Guidelines from the American Society of
Transplantation Infectious Diseases Community of Practice. Clin Transplant., Sep, 33(9), e13543.
[17] de Macedo, P. M., Freitas, D. F. S., Varon, A. G., Lamas, C. da C., Ferreira, L. C. F., Freitas, A.
d’Avila, et al. (2020). COVID-19 and acute juvenile paracoccidioidomycosis coinfection.
PLoS Negl Trop Dis., Aug 10, 14(8), e0008559.
[18] Kousha, M., Tadi, R., and Soubani, A. O. (2011). Pulmonary aspergillosis: a clinical review.
Eur Respir Rev., Sep 1, 20(121), 156–174.
[19] Jeong, W., Keighley, C., Wolfe, R., Lee, W. L., Slavin, M. A., Kong, D. C. M., et al. (2019). The
epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of
case reports. Clin Microbiol Infect., Jan, 25(1), 26–34.
[20] Aslam, S., and Rotstein, C. (2019). AST Infectious Disease Community of Practice. Candida infections
in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious
Diseases Community of Practice. Clin Transplant., Sep, 33(9), e13623.
[21] Tissot, F., Agrawal, S., Pagano, L., Petrikkos, G., Groll, A. H., Skiada, A., et al. (2017). ECIL-6
guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and
hematopoietic stem cell transplant patients. Haematologica., Mar, 102(3), 433–444.
[22] Launay, O., Lortholary, O., Bouges-Michel, C., Jarrousse, B., Bentata, M., and Guillevin, L. (1998).
Candidemia: a nosocomial complication in adults with late-stage AIDS.
Clin Infect Dis., May, 26(5), 1134–1141.
[23] Henriet, S., Verweij, P. E., Holland, S. M., and Warris, A. (2013). Invasive fungal infections in patients
with chronic granulomatous disease. Adv Exp Med Biol., 764, 27–55.
[24] Huang, L., Zhang, N., Huang, X., Xiong, S., Feng, Y., Zhang, Y., et al. (2019). Invasive pulmonary
aspergillosis in patients with influenza infection: A retrospective study and review of the literature.
Clin Respir J., Apr, 13(4), 202–211.
[25] Schwartz, I. S. (2020). High rates of influenza-associated invasive pulmonary aspergillosis may not be
universal: aretrospective cohort study from Alberta, Canada. Clin Infect Dis., Oct 1, 71(7), 1760–1763.
[26] Bhanuprasad, K., Manesh, A., Devasagayam, E., Varghese, L, Cherian, L. M., Kurien, R., et al. (2021).
Risk factors associated with the mucormycosis epidemic during the COVID-19 pandemic. Int J Infect
Dis., Oct, 111, 267–270.
[27] Poissy, J., Damonti, L., Bignon, A., Khanna, N., Von Kietzell, M., Boggian, K., et al. (2020). Risk
factors for candidemia: a prospective matched case-control study. Crit Care., Mar 18, 24(1), 109.
[28] Pakdel, F., Ahmadikia, K., Salehi, M., Tabari, A., Jafari, R., Mehrparvar, G., et al. (2021).
Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.
Mycoses., Oct, 64(10), 1238–1252.
[29] Dupont, D., Menotti, J., Turc, J., Miossec, C., Wallet, F., Richard, J-C., et al. (2021). Pulmonary
aspergillosis in critically ill patients with Coronavirus Disease 2019 (COVID-19).
Med Mycol., Jan 4, 59(1), 110–114.
[30] Salehi, M., Ahmadikia, K., Mahmoudi, S., Kalantari, S., Jamalimoghadamsiahkali, S., Izadi, A., et al.
(2020). Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: Species identification
and antifungal susceptibility pattern. Mycoses., Aug, 63(8), 771–778.
[31] Alegre-González, D., Herrera, S., Bernal, J., Soriano, A., and Bodro, M. (2021). Disseminated
Cryptococcus neoformans infection associated to COVID-19. Med Mycol Case Rep., Dec, 34, 35–37.
[32] Thyagarajan, R. V., Mondy, K. E., and Rose, D. T. (2021). Cryptococcus neoformans blood stream
infection in severe COVID-19 pneumonia. IDCases., Aug 31, 26, e01274.
[33] Gamon, E., Tammena, D., Wattenberg, M., and Augenstein, T. (2021). [Rare superinfection in a
COVID-19 patient-A chronology]. Anaesthesist., 2022 Jan;71(1):38-49. Epub 2021 Aug 24.
[34] Gil, Y., Gil, Y. D., and Markou, T. (2021). The Emergence of Cryptococcemia in COVID-19 Infection:
A Case Report. Cureus., Nov 20, 13(11), e19761.
[35] Thota, D. R., Ray, B., Hasan, M., and Sharma, K. (2022). Cryptococcal Meningoencephalitis During
Convalescence from Severe COVID-19 Pneumonia. Neurohospitalist., Jan, 12(1), 96–99.
[36] Khatib, M. Y., Ahmed, A. A., Shaat, S. B., Mohamed, A. S, and Nashwan, A. J. (2021).
Cryptococcemia in a patient with COVID-19: A case report. Clin Case Rep., Feb, 9(2), 853–855.
[37] Traver, E. C., and Malavé Sánchez, M. (2022). Pulmonary aspergillosis and cryptococcosis as a
complication of COVID-19. Med Mycol Case Rep., Mar, 35, 22–25.
[38] Karnik, K., Wu, Y., Ruddy, S., Quijano-Rondan, B., Urban, C., Turett, G., et al. (2022). Fatal case of
disseminated cryptococcal infection and meningoencephalitis in the setting of prolonged
glucocorticoid use in a Covid-19 positive patient. IDCases., Jan 6, 27, e01380.
[39] RECOVERY Collaborative Group, Horby, P., Lim, W. S., Emberson, J. R., Mafham, M., Bell, J. L.,
et al. (2021). Dexamethasone in Hospitalized Patients with Covid-19.
N Engl J Med., Feb 25, 384(8), 693–704.
[40] Clinical Management Summary. NIH COVID-19 Treatment Guidelines [Internet]. [cited 2022 Jan 17];
Available from: https://files.covid19treatmentguidelines.nih.gov/guidelines/section/section_100.pdf.
[41] Arnow, P. M., Andersen R. L., Mainous P. D., and Smith E. J. (1978). Pumonary aspergillosis during
hospital renovation. Am Rev Respir Dis., Jul, 118(1), 49–53.
[42] Chazalet, V., Debeaupuis, J. P., Sarfati, J., Lortholary, J., Ribaud, P., Shah, P., et al. (1998). Molecular
typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings. J
Clin Microbiol., Jun, 36(6), 1494–1500.
[43] Dewhurst, A. G., Cooper, M. J., Khan, S. M., Pallett, A. P., and Dathan, J. R. (1990). Invasive
aspergillosis in immunosuppressed patients: potential hazard of hospital building work. BMJ., Oct 6,
301(6755), 802–804.
[44] Latgé, J. P. (1999). Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev., Apr, 12(2), 310–350.
[45] Basich, J. E., Graves, T. S., Baz, M. N., Scanlon, G., Hoffmann, R. G., Patterson, R., et al. (1981).
Allergic bronchopulmonary aspergillosis in corticosteroid-dependent asthmatics. J Allergy Clin
Immunol., Aug, 68(2), 98–102.
[46] Knutsen, A. P., and Slavin, R. G. (1991). Allergic bronchopulmonary aspergillosis in patients with
cystic fibrosis. Clin Rev Allergy., 9(1-2), 103–118.
[47] Thompson Iii, G. R., Cornely, O. A., Pappas, P. G., Patterson, T. F., Hoenigl, M., Jenks, J. D., et al.
(2020). Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19. Open Forum
Infect Dis., Jul, 7(7), ofaa242.
[48] Bartoletti, M., Pascale, R., Cricca, M., Rinaldi, M., Maccaro A., Bussini, L., et al. (2021).
Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A
Prospective Study. Clin Infect Dis., Dec 6, 73(11), e3606–e3614.
[49] Nasri, E., Shoaei, P., Vakili, B., Mirhendi, H., Sadeghi, S., Hajiahmadi, S., et al. (2020). Fatal Invasive
Pulmonary Aspergillosis in COVID-19 Patient with Acute Myeloid Leukemia in Iran.
Mycopathologia., Dec, 185(6), 1077–1084.
[50] Morens, D. M., Taubenberger, J. K., and Fauci, A. S. (2008). Predominant role of bacterial pneumonia
as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect
Dis., Oct 1, 198(7), 962–970.
[51] WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne, J. A. C.,
Murthy, S., Diaz, J. V., Slutsky, A. S., Villar, J., et al. (2020). Association Between Administration of
Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta analysis.
JAMA., Oct 6, 324(13), 1330–1341.
[52] Lamoth, F., Lewis, R. E., Walsh, T. J., and Kontoyiannis, D. P. (2021). Navigating the uncertainties of
COVID-19 associated aspergillosis (CAPA): A comparison with influenza associated aspergillosis
(IAPA). J Infect Dis., Mar 26;
[53] Schaffner, A. (1994). Macrophage-Aspergillus interactions. Immunol Ser., 60, 545–552.
[54] Meier-Osusky, I., Schoedon, G., Bläuer, F., Schneemann, M., and Schaffner, A. (1996). Comparison
of the antimicrobial activity of deactivated human macrophages challenged with Aspergillus fumigatus
and Listeria monocytogenes. J Infect Dis., Sep, 174(3), 651–654.
[55] Cağlar, K., Kalkancı, A., Fidan, I., Aydoğan, S., Hızel, K., Dizbay, M., et al. (2011). [Investigation of
interleukin-10, tumor necrosis factor-alpha and interferon-gamma expression in experimental model of
pulmonary aspergillosis]. Mikrobiyol Bul., Apr, 45(2), 344–352.
[56] Fu, Y., Cheng, Y., and Wu, Y. (2020). Understanding SARS-CoV-2-Mediated Inflammatory
Responses: From Mechanisms to Potential Therapeutic Tools. Virol Sin., Jun, 35(3), 266–271.
[57] Yu, X., Zhang, X., Zhao, B., Wang, J., Zhu, Z., Teng, Z., et al. (2011). Intensive cytokine induction in
pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6. PLoS
One., Dec 9, 6(12), e28680.
[58] Su, H., Li, C., Wang, Y., Li, Y., Dong, L., Li, L., et al. (2019). Kinetic host defense of the mice infected
with Aspergillus Fumigatus. Future Microbiol., May, 14, 705–716.
[59] Meduri, G. U., Headley, S., Kohler, G., Stentz, F., Tolley, E., Umberger, R., et al. (1995). Persistent
elevation of inflammatory cytokines predicts a poor outcome in ARDS.
Chest., Apr, 107(4), 1062–1073.
[60] Dimopoulos, G., Almyroudi, M. P., Myrianthefs, P. and Rello, J. (2021). COVID-19-Associated
Pulmonary Aspergillosis (CAPA). Journal of Intensive Medicine., Oct, 1(2), 71-80.
[61] Verweij, P. E., Oakley, K. L., Morrissey, J., Morrissey, G., and Denning, D. W. (1998). Efficacy of
LY303366 against amphotericin B-susceptible and -resistant Aspergillus fumigatus in a murine model
of invasive aspergillosis. Antimicrob Agents Chemother., Apr, 42(4), 873–878.
[62] Eichner, R. D., Al Salami, M., Wood, P. R., and Müllbacher, A. (1986). The effect of gliotoxin upon
macrophage function. Int J Immunopharmacol., 8(7), 789–797.
[63] Chong, W. H., and Neu, K. P. (2021). Incidence, diagnosis and outcomes of COVID-19-associated
pulmonary aspergillosis (CAPA): a systematic review. J Hosp Infect., Jul, 113, 115–129.
[64] Verweij, P. E., Brüggemann, R. J. M., Azoulay, E., Bassetti, M., Blot, S., Buil, J. B., et al. (2021).
Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary
aspergillosis. Intensive Care Med., Aug, 47(8), 819–834.
[65] Van Biesen, S., Kwa, D., Bosman, R. J., and Juffermans, N. P. (2020). Detection of Invasive Pulmonary
Aspergillosis in COVID-19 with Non-directed Bronchoalveolar Lavage.
Am J Respir Crit Care Med., Jul 15.
[66] Chong, G-L. M., van de Sande, W. W. J., Dingemans, G. J. H., Gaajetaan, G. R., Vonk, A. G., Hayette,
M-P., et al. (2015). Validation of a new Aspergillus real-time PCR assay for direct detection of
Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid. J Clin
Microbiol., Mar, 53(3), 868–874.
[67] Costantini, C., van de Veerdonk, F. L., and Romani, L. (2020). Covid-19-Associated Pulmonary
Aspergillosis: The Other Side of the Coin. Vaccines (Basel). Dec 1, 8(4).
[68] Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., et al. (2020). Epidemiological and clinical
characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.
Lancet., Feb 15, 395(10223), 507–513.
[69] Alanio, A., Dellière, S., Fodil, S., Bretagne, S., and Mégarbane, B. (2020). Prevalence of putative
invasive pulmonary aspergillosis in critically ill patients with COVID-19.
Lancet Respir Med., Jun, 8(6), e48–e49.
[70] Nguyen, L. S., Dolladille, C., Drici, M-D., Fenioux, C., Alexandre, J., Mira, J. P., et al. (2020).
Cardiovascular toxicities associated with hydroxychloroquine and azithromycin: an analysis of the
world health organization pharmacovigilance database. Circulation., Jul 21, 142(3), 303–305.
[71] Tabassum, T., Araf, Y., Moin, A. T., Rahaman, T. I., and Hosen, M. J. (2021). COVID-19-associated
mucormycosis: possible role of free iron uptake and immunosuppression.
Mol Biol Rep., 49(1):747-754 Oct 28.
[72] Farmakiotis, D., and Kontoyiannis, D. P. (2016). Mucormycoses. Infect Dis Clin
North Am., Mar, 30(1), 143–163.
[73] Skiada, A., Pagano, L., Groll, A., Zimmerli, S., Dupont, B., Lagrou, K., et al. (2011). Zygomycosis in
Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical
Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect.,
Dec 1, 17(12), 1859–1867.
[74] Divakar, P. K. (2021). Fungal Taxa Responsible for Mucormycosis/“Black Fungus”
among COVID 19 Patients in India. J Fungi (Basel). Aug 7, 7(8).
[75] Colombo, A. (2021). Micoses Emergentes e Reemergentes relacionadas ao SARS-CoV-2. IV Simposio:
Infeccoes Emergentes e Reemergentes no Brasil; Mar 9. [Emerging and Reemerging Mycoses Related
to SARS-CoV-2. IV Symposium: Emerging and Reemerging Infections in Brazil; Mar 9].
[76] Agoramoorthy, G. (2021). India’s Second Wave of Coronavirus Disease 2019 (COVID-19) and the
Lethal Outbreak of Black Fungus Infection. Arch Pathol Lab Med., Jul 29. 145(10):1191-1192.
[77] IDF Atlas 9th edition and other resources [Internet]. [cited 2021 Sep 5]. Available from:
https://www.diabetesatlas.org/en/resources/.
[78] Pal, R., Singh, B., Bhadada, S. K., Banerjee, M., Bhogal, R. S., Hage, N, et al. (2021). COVID-19-
associated mucormycosis: An updated systematic review of literature. Mycoses., Dec;64(12):1452-
1459. Epub 2021 Jun 16.
[79] Müller, J. A., Groß, R., Conzelmann, C., Krüger, J., Merle, U., Steinhart, J., et al. (2021).
SARS-CoV 2 infects and replicates in cells of the human endocrine and exocrine pancreas.
Nat Metab., Feb 3, 3(2), 149–165.
[80] Ellingsgaard, H., Hauselmann, I., Schuler, B., Habib, A. M., Baggio, L. L., Meier, D. T., et al. (2011).
Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells
and alpha cells. Nat Med., Oct 30, 17(11), 1481–1489.
[81] Costela-Ruiz, V. J., Illescas-Montes, R., Puerta-Puerta, J. M., Ruiz, C., and Melguizo-Rodríguez, L.
(2020). SARS-CoV-2 infection: The role of cytokines in COVID-19 disease.
Cytokine Growth Factor Rev., Aug, 54, 62–75.
[82] Chiasson, J. L., Aris-Jilwan, N., Bélanger, R., Bertrand, S., Beauregard, H., Ekoé, J. M., et al. (2003).
Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Can Med
Assoc J., Apr 1, 168(7), 859–866.
[83] Anand, V. K., Alemar, G., and Griswold, J. A. (1992). Intracranial complications of mucormycosis: an
experimental model and clinical review. Laryngoscope., Jun, 102(6), 656–662.
[84] Gebremariam, T., Liu, M., Luo, G., Bruno, V., Phan, Q. T., Waring, A. J., et al. (2014). CotH3 mediates
fungal invasion of host cells during mucormycosis. J Clin Invest., Jan, 124(1), 237–250.
[85] Roilides, E., Antachopoulos, C., and Simitsopoulou, M. (2014). Pathogenesis and host defence against
Mucorales: the role of cytokines and interaction with antifungal drugs. Mycoses., Dec, 57 Suppl 3, 40–47.
[86] Gebremariam, T., Lin, L., Liu, M., Kontoyiannis, D. P., French, S., Edwards, J. E., et al. (2016).
Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis.
J Clin Invest., Jun 1, 126(6), 2280–2294.
[87] Chinn, R. Y., and Diamond, R. D. (1982). Generation of chemotactic factors by Rhizopus oryzae in
the presence and absence of serum: relationship to hyphal damage mediated by human neutrophils and
effects of hyperglycemia and ketoacidosis. Infect Immun., Dec, 38(3), 1123–1129.
[88] Shirazi, F., and Kontoyiannis, D. P., Ibrahim, A. S. (2015). Iron starvation induces apoptosis in
Rhizopus oryzae in vitro. Virulence., 6(2), 121–126.
[89] Ibrahim, A. S., Spellberg, B., and Edwards, J. (2008). Iron acquisition: a novel perspective on
mucormycosis pathogenesis and treatment. Curr Opin Infect Dis., Dec, 21(6), 620–625.
[90] Camaschella, C., Nai, A., and Silvestri, L. (2020). Iron metabolism and iron disorders revisited in the
hepcidin era. Haematologica., Jan 31, 105(2), 260–272.
[91] Takami, T., and Sakaida, I. (2011). Iron regulation by hepatocytes and free radicals.
J Clin Biochem Nutr., Mar, 48(2), 103–106.
[92] Petrikkos, G., and Tsioutis, C. (2018). Recent advances in the pathogenesis of mucormycoses.
Clin Ther., Jun, 40(6), 894–902.
[93] Lukins, M. B., and Manninen, P. H. (2005). Hyperglycemia in patients administered dexamethasone
for craniotomy. Anesth Analg., Apr, 100(4), 1129–1133.
[94] Perez, A., Jansen-Chaparro, S., Saigi, I., Bernal-Lopez, M. R., Miñambres, I., and Gomez-Huelgas, R.
(2014). Glucocorticoid-induced hyperglycemia. J Diabetes., Jan, 6(1), 9–20.
[95] Thaiss, C. A., Levy, M., Grosheva, I., Zheng, D., Soffer, E., Blacher, E., et al. (2018). Hyperglycemia
drives intestinal barrier dysfunction and risk for enteric infection. Science.,
Mar 23, 359(6382), 1376–1383.
[96] Banerjee, M., and Pal, R., Bhadada, S. K. (2021). Intercepting the deadly trinity of mucormycosis,
diabetes and COVID-19 in India. Postgrad Med J., Jun 8.
[97] Rammaert, B., Lanternier, F., Zahar, J-R., Dannaoui, E., Bougnoux, M. E., Lecuit, M., et al. (2012).
Healthcare-associated mucormycosis. Clin Infect Dis., Feb 1, 54 Suppl 1, S44–54.
[98] Choksi, T., Agrawal, A., Date, P., Rathod, D., Gharat, A., Ingole, A., et al. (2021). Cumulative
Mortality and Factors Associated with Outcomes of Mucormycosis After COVID-19 at a
Multispecialty Tertiary Care Center in India. JAMA Ophthalmol., Dec 9. 140(1):66-72.
[99] Kullberg, B. J., and Arendrup, M. C. (2015). Invasive Candidiasis.
N Engl J Med., Oct 8, 373(15), 1445–1456.
[100] Pappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L., and Kullberg, B. J. (2018).
Invasive candidiasis. Nat Rev Dis Primers., May 11, 4, 18026.
[101] Ben-Ami, R., Berman, J., Novikov, A., Bash, E., Shachor-Meyouhas, Y., Zakin, S., et al. (2017).
Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel.
Emerging Infect Dis., Feb, 23(1).
[102] Marra, A. R., Camargo, L. F. A., Pignatari, A. C. C., Sukiennik, T., Behar, P. R. P., Medeiros, E. A.
S., et al. (2011). Nosocomial bloodstream infections in Brazilian hospitals: analysis of 2,563 cases from
a prospective nationwide surveillance study. J Clin Microbiol., May, 49(5), 1866–1871.
[103] Nucci, M., Barreiros, G., Guimarães, L. F., Deriquehem, V. A. S., Castiñeiras, A. C., and Nouér, S. A.
(2021). Increased incidence of candidemia in a tertiary care hospital with the COVID-19 pandemic.
Mycoses., Feb, 64(2), 152–156.
[104] Macauley, P., and Epelbaum, O. (2021). Epidemiology and Mycology of Candidaemia
in non oncological medical intensive care unit patients in a tertiary center in the United States: Overall analysis
and comparison between non-COVID-19 and COVID-19 cases. Mycoses., Jun, 64(6), 634–640.
[105] de Almeida, J. N., Francisco, E. C., Hagen, F., Brandão, I. B., Pereira, F. M., Presta Dias, P. H., et al.
(2021). Emergence of Candida auris in Brazil in a COVID-19
Intensive Care Unit. J Fungi (Basel). Mar 17, 7(3).
[106] Arastehfar, A., Carvalho, A., Nguyen, M. H., Hedayati, M. T., Netea, M. G., Perlin, D. S., et al. (2020).
COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of
Immunological Predispositions? J Fungi (Basel). Oct 8, 6(4).
[107] Chow, N. A., Gade, L., Tsay, S. V., Forsberg, K., Greenko, J. A., Southwick, K. L., et al. (2018).
Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA:
a molecular epidemiological survey. Lancet Infect Dis., Dec, 18(12), 1377–1384.
[108] Azoulay, E., Timsit, J-F., Tafflet, M., de Lassence, A., Darmon, M., Zahar, J. R., et al. (2006). Candida
colonization of the respiratory tract and subsequent pseudomonas
ventilator-associated pneumonia. Chest., Jan, 129(1), 110–117.
[109] Prestel, C., Anderson, E., Forsberg, K., Lyman, M., de Perio, M. A., Kuhar, D., et al. (2021). Candida
auris Outbreak in a COVID-19 Specialty Care Unit – Florida, July-August 2020.
MMWR Morb Mortal Wkly Rep., Jan 15, 70(2), 56–57.
[110] Nobrega de Almeida, J., Brandão, I. B., Francisco, E. C., de Almeida, S. L. R., de Oliveira Dias, P.,
Pereira, F. M., et al. (2021). Axillary Digital Thermometers uplifted a multidrug-susceptible Candida
auris outbreak among COVID-19 patients in Brazil. Mycoses., Sep, 64(9), 1062–1072.
[111] LAC DPH Health Advisory: Resurgence of Candida auris in Los Angeles County. Key Messages.
[112] Ziegler, C. G. K., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., et al. (2020).
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and
Is Detected in Specific Cell Subsets across Tissues. Cell., May 28, 181(5), 1016–1035.e19.
[113] Wang, W., Xu, Y., Gao, R., Lu, R., Han, K., Wu, G., et al. (2020). Detection of SARS-CoV-2 in
Different Types of Clinical Specimens. JAMA., May 12, 323(18), 1843–1844.
[114] Lamers, M. M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T. I., et al. (2020).
SARS-CoV-2 productively infects human gut enterocytes. Science., Jul 3, 369(6499), 50–54.
[115] Kim, H. S. (2021). Do an Altered Gut Microbiota and an
Associated Leaky Gut Affect COVID-19 Severity? MBio., Jan 12, 12(1).
[116] Effenberger, M., Grabherr, F., Mayr, L., Schwaerzler, J., Nairz, M., Seifert, M., et al. (2020). Faecal
calprotectin indicates intestinal inflammation in COVID-19. Gut., Aug, 69(8), 1543–1544.
[117] Kayaaslan, B., Eser, F., Kaya Kalem, A., Bilgic, Z., Asilturk, D., Hasanoglu, I., et al. (2021).
Characteristics of candidemia in COVID-19 patients; increased incidence, earlier occurrence and
higher mortality rates compared to non-COVID-19 patients. Mycoses., Sep, 64(9), 1083–1091.
[118] Arastehfar, A., Shaban, T., Zarrinfar, H., Roudbary, M., Ghazanfari, M., Hedayati, M. T., et al. (2021).
Candidemia among Iranian Patients with Severe COVID-19 Admitted to ICUs. J Fungi (Basel). Apr 8, 7(4).
[119] Pfaller, M. A., Diekema, D. J., Gibbs, D. L., Newell, V. A., Ellis, D., Tullio, V., et al. (2010). Results
from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis
of susceptibilities of Candida Species to fluconazole and voriconazole as determined by CLSI
standardized disk diffusion. J Clin Microbiol., Apr, 48(4), 1366–1377.
[120] Sanguinetti, M., Posteraro, B., and Lass-Flörl, C. (2015). Antifungal drug resistance among Candida
species: mechanisms and clinical impact. Mycoses., Jun, 58 Suppl 2, 2–13.
[121] Ostrowsky, B., Greenko, J., Adams, E., Quinn, M., O’Brien, B., Chaturvedi, V., et al. (2020). Candida
auris Isolates Resistant to Three Classes of Antifungal Medications – New York, 2019. MMWR Morb
Mortal Wkly Rep., Jan 10, 69(1), 6–9.
[122] Beyda, N. D., John, J., Kilic, A., Alam, M. J., Lasco, T. M., and Garey, K. W. (2014). FKS mutant
Candida glabrata: risk factors and outcomes in patients with candidemia.
Clin Infect Dis., Sep 15, 59(6), 819–825.
[123] Posteraro, B., Torelli, R., Vella, A., Leone, P. M., De Angelis, G., De Carolis, E., et al. (2020).
Pan Echinocandin-Resistant Candida glabrata Bloodstream Infection
Complicating COVID-19: A Fatal Case Report. J Fungi (Basel). Sep 6, 6(3).