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Fungal Infections Complicating COVID-19
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Fungal Infections Complicating COVID-19

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (1 August 2020) | Viewed by 72848

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Martin Hoenigl

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Guest Editor
1. Division of Infectious Diseases and Global Public Helath; University of California, San Diego, CA, USA
2. Section of Infectious Diseases and Tropical Medicine and Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
Interests: clinical mycology; mold infection; aspergillosis
Special Issues, Collections and Topics in MDPI journals
Dr. Alida Fe Talento

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Guest Editor
1. Department of Microbiology, Our Lady of Lourdes Hospital Drogheda and Beaumont Hospital, Louth, Ireland
2. Department of Clinical Microbiology, Royal College of Surgeons, Dublin, Ireland
Interests: clinical mycology; aspergillosis; candidiasis; antifungal stewardship

Special Issue Information

Dear Colleagues,

This Special Issue will be dedicated to fungal infections complicating coronavirus disease 2019 (COVID-19).

Opportunistic infections following respiratory viral infections has been recognized since the 1918 influenza pandemic. Although the vast majority of COVID-19 cases are mild to moderate, approximately 15% of patients diagnosed with COVID-19 require hospitalization and supplementary oxygen, and 5% of patients develop critical disease with acute respiratory distress syndrome (ARDS) and require ICU admission. ARDS may also be a consequence of infections with other respiratory viruses, like influenza, where invasive pulmonary aspergillosis (IPA) occurs in up to one-third of critical ill patients. Although the pathophysiology of COVID-19 is not completely understood, it is plausible that immune dysregulation and lung damage stemming from COVID-19 immunopathology facilitate Aspergillus superinfection in a way that is at least partially distinct from other respiratory viruses. From Wuhan, epidemiological studies indicate that invasive fungal infections may occur in between 4–5% of COVID-19 episodes requiring ICU admission. Given that in Wuhan galactomannan testing is rarely available and fungal diagnostics are sparse, this is likely an underestimate of the real burden of IPA in patients with COVID-19 requiring ICU admission. Recent reports from Europe indicate that IPA may occur in up to 30% of COVID-19 patients requiring ICU admission.

This Special Issue will focus on fungal infections complicating COVID-19, ranging from basic science papers elucidating pathophysiology and immunology, including mycobiome studies; to diagnostic studies evaluating microbiological and clinical/radiological findings; to clinical studies and observations (including case reports and case series) of fungal infections complicating COVID-19. While the primary focus will be invasive fungal infections, large case series of non-invasive fungal infections (e.g. thrush) will be considered as well. 

Prof. Dr. Martin Hoenigl
Dr. Alida Fe Talento
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • COVID-19
  • SARS-CoV-2
  • galactomannan
  • radiology
  • aspergillosis
  • thrush
  • candidiasis
  • intensive care
  • mycobiome
  • antifungals
  • antifungal resistance

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Published Papers (8 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 168 KiB  
Editorial
Fungal Infections Complicating COVID-19: With the Rain Comes the Spores
by Alida Fe Talento and Martin Hoenigl
J. Fungi 2020, 6(4), 279; https://doi.org/10.3390/jof6040279 - 11 Nov 2020
Cited by 15 | Viewed by 2987
Abstract
Within the last 12 months, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread globally to pandemic proportions [...] Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)

Research

Jump to: Editorial, Review, Other

12 pages, 1105 KiB  
Article
Is the COVID-19 Pandemic a Good Time to Include Aspergillus Molecular Detection to Categorize Aspergillosis in ICU Patients? A Monocentric Experience
by Jean-Pierre Gangneux, Florian Reizine, Hélène Guegan, Kieran Pinceaux, Pierre Le Balch, Emilie Prat, Romain Pelletier, Sorya Belaz, Mathieu Le Souhaitier, Yves Le Tulzo, Philippe Seguin, Mathieu Lederlin, Jean-Marc Tadié and Florence Robert-Gangneux
J. Fungi 2020, 6(3), 105; https://doi.org/10.3390/jof6030105 - 10 Jul 2020
Cited by 61 | Viewed by 5965
Abstract
(1) Background: The diagnosis of invasive aspergillosis (IA) in an intensive care unit (ICU) remains a challenge and the COVID-19 epidemic makes it even harder. Here, we evaluated Aspergillus PCR input to help classifying IA in SARS-CoV-2-infected patients. (2) Methods: 45 COVID-19 patients [...] Read more.
(1) Background: The diagnosis of invasive aspergillosis (IA) in an intensive care unit (ICU) remains a challenge and the COVID-19 epidemic makes it even harder. Here, we evaluated Aspergillus PCR input to help classifying IA in SARS-CoV-2-infected patients. (2) Methods: 45 COVID-19 patients were prospectively monitored twice weekly for Aspergillus markers and anti-Aspergillus serology. We evaluated the concordance between (I) Aspergillus PCR and culture in respiratory samples, and (II) blood PCR and serum galactomannan. Patients were classified as putative/proven/colonized using AspICU algorithm and two other methods. (3) Results: The concordance of techniques applied on respiratory and blood samples was moderate (kappa = 0.58 and kappa = 0.63, respectively), with a higher sensitivity of PCR. According to AspICU, 9/45 patients were classified as putative IA. When incorporating PCR results, 15 were putative IA because they met all criteria, probably with a lack of specificity in the context of COVID-19. Using a modified AspICU algorithm, eight patients were classified as colonized and seven as putative IA. (4) Conclusion: An appreciation of the fungal burden using PCR and Aspergillus serology was added to propose a modified AspICU algorithm. This proof of concept seemed relevant, as it was in agreement with the outcome of patients, but will need validation in larger cohorts. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
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Review

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13 pages, 263 KiB  
Review
COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?
by Amir Arastehfar, Agostinho Carvalho, M. Hong Nguyen, Mohammad Taghi Hedayati, Mihai G. Netea, David S. Perlin and Martin Hoenigl
J. Fungi 2020, 6(4), 211; https://doi.org/10.3390/jof6040211 - 8 Oct 2020
Cited by 177 | Viewed by 12268
Abstract
The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal [...] Read more.
The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida. This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata call for the development of new antifungal drugs with novel mechanisms of action. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
14 pages, 304 KiB  
Review
COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges
by Aia Mohamed, Thomas R. Rogers and Alida Fe Talento
J. Fungi 2020, 6(3), 115; https://doi.org/10.3390/jof6030115 - 22 Jul 2020
Cited by 57 | Viewed by 7366
Abstract
Aspergillus co-infection in patients with severe coronavirus disease 2019 (COVID-19) pneumonia, leading to acute respiratory distress syndrome, has recently been reported. To date, 38 cases have been reported, with other cases most likely undiagnosed mainly due to a lack of clinical awareness and [...] Read more.
Aspergillus co-infection in patients with severe coronavirus disease 2019 (COVID-19) pneumonia, leading to acute respiratory distress syndrome, has recently been reported. To date, 38 cases have been reported, with other cases most likely undiagnosed mainly due to a lack of clinical awareness and diagnostic screening. Importantly, there is currently no agreed case definition of COVID-19 associated invasive pulmonary aspergillosis (CAPA) that could aid in the early detection of this co-infection. Additionally, with the global emergence of triazole resistance, we emphasize the importance of antifungal susceptibility testing in order to ensure appropriate antifungal therapy. Herein is a review of 38 published CAPA cases, which highlights the diagnostic and therapeutic challenges posed by this novel fungal co-infection. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
17 pages, 339 KiB  
Review
COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From Immunology to Treatment
by Amir Arastehfar, Agostinho Carvalho, Frank L. van de Veerdonk, Jeffrey D. Jenks, Philipp Koehler, Robert Krause, Oliver A. Cornely, David S. Perlin, Cornelia Lass-Flörl and Martin Hoenigl
J. Fungi 2020, 6(2), 91; https://doi.org/10.3390/jof6020091 - 24 Jun 2020
Cited by 286 | Viewed by 18842
Abstract
Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated [...] Read more.
Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)

Other

11 pages, 890 KiB  
Case Report
Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report
by Brunella Posteraro, Riccardo Torelli, Antonietta Vella, Paolo Maria Leone, Giulia De Angelis, Elena De Carolis, Giulio Ventura, Maurizio Sanguinetti and Massimo Fantoni
J. Fungi 2020, 6(3), 163; https://doi.org/10.3390/jof6030163 - 6 Sep 2020
Cited by 74 | Viewed by 5738
Abstract
Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due [...] Read more.
Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly due to multidrug-resistant Gram-negative bacteria, and lastly due to a possibly fatal Candida glabrata. The development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
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7 pages, 232 KiB  
Case Report
Bloodstream Infection by Saccharomyces cerevisiae in Two COVID-19 Patients after Receiving Supplementation of Saccharomyces in the ICU
by Ioannis Ventoulis, Theopisti Sarmourli, Pinelopi Amoiridou, Paraskevi Mantzana, Maria Exindari, Georgia Gioula and Timoleon-Achilleas Vyzantiadis
J. Fungi 2020, 6(3), 98; https://doi.org/10.3390/jof6030098 - 30 Jun 2020
Cited by 60 | Viewed by 7392
Abstract
Co-infections have an unknown impact on the morbidity and mortality of the new clinical syndrome called coronavirus disease 2019 (COVID-19). The syndrome is caused by the new pandemic coronavirus SARS-CoV-2 and it is probably connected with severe traces in the elements of the [...] Read more.
Co-infections have an unknown impact on the morbidity and mortality of the new clinical syndrome called coronavirus disease 2019 (COVID-19). The syndrome is caused by the new pandemic coronavirus SARS-CoV-2 and it is probably connected with severe traces in the elements of the immune system. Apart from possible Aspergillus infections, particularly in patients with acute respiratory distress syndrome (ARDS), other fungal infections could occur, probably more easily, due to the immunological dysregulation and the critical condition of these patients. Probiotic preparations of Saccharomyces are broadly used for the prevention of antibiotic-associated complications, especially in the intensive care units (ICU). On the other hand, Saccharomyces organisms are reported as agents of invasive infection in immunocompromised or critically ill patients. We report two cases of bloodstream infection by Saccharomyces in two patients hospitalised in the ICU, due to severe COVID-19, after Saccharomyces supplementation. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
8 pages, 1437 KiB  
Case Report
Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report
by Eelco F. J. Meijer, Anton S. M. Dofferhoff, Oscar Hoiting, Jochem B. Buil and Jacques F. Meis
J. Fungi 2020, 6(2), 79; https://doi.org/10.3390/jof6020079 - 6 Jun 2020
Cited by 81 | Viewed by 9084
Abstract
COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In addition, the emergence of resistance to triazole antifungal agents puts [...] Read more.
COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In addition, the emergence of resistance to triazole antifungal agents puts emphasis on early surveillance for azole-resistant Aspergillus species. We present a patient with putative CAPA due to Aspergillus fumigatus with identification of a triazole-resistant isolate during therapy. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole resistance. Full article
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
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