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Fungal Infections in COVID-19 Patients

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A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 14064

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Special Issue Editors

Prof. Dr. Spinello Antinori

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Guest Editor

Luigi Sacco Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milano, Italy
Interests: infectious diseases; invasive aspergillosis; cryptococcosis; histoplasmosis; fungal infections in immunocompromised hosts

Prof. Dr. Francesco Barchiesi

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Guest Editor

1. Dipartimento di Scienze Biomediche e Sanità Pubblica, Università Politecnica delle Marche, Ancona, Italy
2. Malattie Infettive, Azienda Ospedaliera Ospedali Marche Nord, 60121 Pesaro, Italy
Interests: antifungal resistance; invasive candidiasis; fungal pathogenesis; invasive aspergillosis; antifungal susceptibility tests

Special Issue Information

Dear Colleagues,

Invasive fungal infections have emerged as important opportunistic diseases among hospitalized subjects affected by severe COVID19. COVID-associated pulmonary aspergillosis (CAPA) has been reported as the leading invasive mycoses, with an incidence ranging from 3 to 35% in mechanically ventilated critically ill patients. However, such wide differences are probably related to different diagnostic criteria adopted with the difficult to separate true invasive disease from colonization. Moreover, more than 3000 cases of rhino-orbitocerebral mucormycosis (CAM) have been descibed in the literature especially in India, as well as in several other countries, suggesting the possibility of an emerging global problem. Candidemia, a frequent secondary infection among ICU-hospitalized patients, has been also increasingly observed in COVID-19 with high mortality; however, it is presently unknown if, besides well-known classical risk factors, specific risk factors for COVID-19 are responsible of its occurrence in this setting. Other invasive fungal infections (i.e., histoplasmosis, cryptococcosis, pneumocystosis, and coccidioidomycosis) have been reported, but are less well characterized among COVID-19 patients.

In this Special Issue, original research articles, reviews, systematic reviews, meta-studies, and case reports on such topics are welcome. Research areas may include the following:

Epidemiology
Pathogenesis
Clinical presentation
Diagnostic methods
Antifungal therapy
Autopsy findings

Prof. Dr. Spinello Antinori
Prof. Dr. Francesco Barchiesi
Guest Editors

Manuscript Submission Information

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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

aspergillosis
mucormycosis
cryptococcosis
candidiasis
pneumocystosis
histoplasmosis
endemic mycoses
SARS-CoV2
COVID-19

Published Papers (7 papers)

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Research

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12 pages, 3684 KiB

Open AccessArticle

Invasive Candidiasis in Adult Patients with COVID-19: Results of a Multicenter Study in St. Petersburg, Russia

by Olga Kozlova, Ekaterina Burygina, Sofya Khostelidi, Olga Shadrivova, Andrey Saturnov, Denis Gusev, Aleksandr Rysev, Anatoliy Zavrazhnov, Maria Vashukova, Galina Pichugina, Mikhail Mitichkin, Sergey Kovyrshin, Tatiana Bogomolova, Yulia Borzova, Ellina Oganesyan, Natalya Vasilyeva, Nikolay Klimko and Working Group

J. Fungi 2023, 9(9), 927; https://doi.org/10.3390/jof9090927 - 14 Sep 2023

Cited by 2 | Viewed by 1069

Abstract

We studied the risk factors, etiology, clinical manifestations, and treatment outcomes of COVID-19-associated invasive candidiasis (COVID-IC) in adult patients admitted to six medical facilities in St. Petersburg. (November 2020–December 2022). In this retrospective study, we included 72 patients with COVID-IC with a median age of 61 years (range 29–96), 51% of whom were women. The predisposing factors for COVID-IC were a central venous catheter (CVC) for more than 10 days (the odds ratio (OR) = 70 [15–309]), abdominal surgical treatment performed in the previous 2 weeks (OR = 8.8 [1.9–40.3]), bacteremia (OR = 10.6 [4.8–23.3]), pulmonary ventilation (OR = 12.9 [5.9–28.4]), and hemodialysis (OR = 11.5 [2.5–50.8]). The signs and symptoms of COVID-IC were non-specific: fever (59%), renal failure (33%), liver failure (23%), and cardiovascular failure (10%). Candida albicans (41%) predominated among the pathogens of the candidemia. The multidrug-resistant Candida species C. auris (23%) and C. glabrata (5%) were also identified. Empirical therapy was used in 21% of COVID-IC patients: azole-93%, echinocandin–7%. The majority of COVID-IC patients (79%) received, after laboratory confirmation of the diagnosis of IC, fluconazole (47%), voriconazole (25%), echinocandin (26%), and amphotericin B (2)%. The 30 days overall survival rate was 45%. The prognosis worsened concomitant bacteremia, hemodialysis, and long-term therapy by systemic glucocorticosteroids (SGCs), bronchial colonization with Candida spp. The survival prognosis was improved by the early change/replacement of CVC (within 24 h), the initiation of empirical therapy, and the use of echinocandin. Conclusions: We highlighted the risk factors that predispose COVID-19 patients to candidiasis and worsen the survival prognosis. Their individual effects in patients with COVID-19 must be well understood to prevent the development of opportunistic co-infections that drastically lower chances of survival. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

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8 pages, 257 KiB

Open AccessCommunication

The Clinical Characteristics of Bloodstream Infections Due to Candida spp. in Patients Hospitalized in Intensive Care Units during the SARS-CoV-2 Pandemic: The Results of a Multicenter Study

by Francesco Pallotta, Lucia Brescini, Arianna Ianovitz, Ilenia Luchetti, Lucia Franca, Benedetta Canovari, Elisabetta Cerutti and Francesco Barchiesi

J. Fungi 2023, 9(6), 642; https://doi.org/10.3390/jof9060642 - 01 Jun 2023

Cited by 2 | Viewed by 1070

Abstract

Candidemia is a serious health threat. Whether this infection has a greater incidence and a higher mortality rate in patients with COVID-19 is still debated. In this multicenter, retrospective, observational study, we aimed to identify the clinical characteristics associated with the 30-day mortality in critically ill patients with candidemia and to define the differences in candidemic patients with and without COVID-19. Over a three-year period (2019–2021), we identified 53 critically ill patients with candidemia, 18 of whom (34%) had COVID-19 and were hospitalized in four ICUs. The most frequent comorbidities were cardiovascular (42%), neurological (17%), chronic pulmonary diseases, chronic kidney failure, and solid tumors (13% each). A significantly higher proportion of COVID-19 patients had pneumonia, ARDS, septic shock, and were undergoing an ECMO procedure. On the contrary, non-COVID-19 patients had undergone previous surgeries and had used TPN more frequently. The mortality rate in the overall population was 43%: 39% and 46% in the COVID-19 and non-COVID-19 patients, respectively. The independent risk factors associated with a higher mortality were CVVH (HR 29.08 [CI 95% 3.37–250]) and a Charlson’s score of > 3 (HR 9.346 [CI 95% 1.054–82.861]). In conclusion, we demonstrated that candidemia still has a high mortality rate in patients admitted to ICUs, irrespective of infection due to SARS-CoV-2. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

7 pages, 244 KiB

Open AccessCommunication

COVID-19 Associated Pulmonary Aspergillosis in Patients on Extracorporeal Membrane Oxygenation Treatment—A Retrospective Study

by Ali Nuh, Newara Ramadan, Lisa Nwankwo, Jackie Donovan, Brijesh Patel, Anand Shah, Sujal R. Desai and Darius Armstrong-James

J. Fungi 2023, 9(4), 398; https://doi.org/10.3390/jof9040398 - 24 Mar 2023

Cited by 3 | Viewed by 1437

Abstract

Background: The incidence and outcome of pulmonary aspergillosis in coronavirus disease (COVID-19) patients on extracorporeal membrane oxygenation (ECMO) are unknown and have not been fully addressed. We investigated the incidence, risk factors and outcome of pulmonary aspergillosis in COVID-19 ECMO patients. In addition, the diagnostic utility of bronchoalveolar lavage fluid and CT scans in this setting were assessed. Methods: We conducted a retrospective study on incidence and outcome of pulmonary aspergillosis in COVID-19 ECMO patients by reviewing clinical, radiological, and mycological evidence. These patients were admitted to a tertiary cardiothoracic centre during the early COVID-19 surge between March 2020 and January 2021. Results and measurements: The study included 88 predominantly male COVID-19 ECMO patients with a median age and a BMI of 48 years and 32 kg/m², respectively. Pulmonary aspergillosis incidence was 10% and was associated with very high mortality. Patients with an Aspergillus infection were almost eight times more likely to die compared with those without infection in multivariate analysis (OR 7.81, 95% CI: 1.20–50.68). BALF GM correlated well with culture results, with a Kappa value of 0.8 (95% CI: 0.6, 1.0). However, serum galactomannan (GM) and serum (1–3)-β-D-glucan (BDG) lacked sensitivity. Thoracic computed tomography (CT) diagnostic utility was also inconclusive, showing nonspecific ground glass opacities in almost all patients. Conclusions: In COVID-19 ECMO patients, pulmonary aspergillosis incidence was 10% and associated with very high mortality. Our results support the role of BALF in the diagnosis of pulmonary aspergillosis in COVID-19 ECMO patients. However, the diagnostic utility of BDG, serum GM, and CT scans is unclear. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

10 pages, 259 KiB

Open AccessArticle

Invasive Fungal Infections in Hospitalized Patients with COVID-19: A Non-Intensive Care Single-Centre Experience during the First Pandemic Waves

by Letizia Cattaneo, Antonio Riccardo Buonomo, Carmine Iacovazzo, Agnese Giaccone, Riccardo Scotto, Giulio Viceconte, Simona Mercinelli, Maria Vargas, Emanuela Roscetto, Francesco Cacciatore, Paola Salvatore, Maria Rosaria Catania, Riccardo Villari, Antonio Cittadini, Ivan Gentile and COVID Federico II Team

J. Fungi 2023, 9(1), 86; https://doi.org/10.3390/jof9010086 - 06 Jan 2023

Cited by 7 | Viewed by 2190

Abstract

Invasive fungal infections (IFIs) represent a severe complication of COVID-19, yet they are under-estimated. We conducted a retrospective analysis including all the COVID-19 patients admitted to the Infectious Diseases Unit of the Federico II University Hospital of Naples until the 1 July 2021. Among 409 patients, we reported seven cases of IFIs by Candida spp., seven of Pneumocystis jirovecii pneumonia, three of invasive pulmonary aspergillosis, and one of Trichosporon asahii. None of the cases presented underlying predisposing conditions, excluding one oncohematological patient treated with rituximab. Ten cases showed lymphopenia with high rates of CD4+ < 200/µL. All cases received high-dose steroid therapy (mean duration 33 days, mean cumulative dosage 1015 mg of prednisone equivalent), and seven cases had severe COVID-19 disease (OSCI ≥ 5) prior to IFI diagnosis. The cases showed a higher overall duration of hospitalization (63 vs 24 days) and higher mortality rate (23% vs. 7%) compared with the COVID-19 patients who did not developed IFIs. Cases showed a higher prevalence of high-dose steroid therapy and lymphopenia with CD4+ < 200/µL, primarily due to SARS-CoV-2 infection and not related to underlying comorbidities. IFIs strongly impact the overall length of hospitalization and mortality. Therefore, clinicians should maintain a high degree of suspicion of IFIs, especially in severe COVID-19 patients. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

10 pages, 1059 KiB

Open AccessArticle

Penicillium digitatum, First Clinical Report in Chile: Fungal Co-Infection in COVID-19 Patient

by Isabel Iturrieta-González, Annesi Giacaman, Patricio Godoy-Martínez, Fernando Vega, Marcela Sepúlveda, Cledir Santos, Valentina Toledo, Gonzalo Rivera, Leandro Ortega, Andrés San Martín, Vitalia Bahamondes, Felipe Collao, Raúl Sánchez and Flery Fonseca-Salamanca

J. Fungi 2022, 8(9), 961; https://doi.org/10.3390/jof8090961 - 14 Sep 2022

Cited by 4 | Viewed by 3741

Abstract

Penicillium digitatum is one of the most important phytopathogens. It causes deterioration and rotting of citrus fruits, generating significant economic losses worldwide. As a human pathogen, it is extremely rare. We present a case of pulmonary co-infection in a patient diagnosed with pneumonia due to SARS-CoV-2. A 20-year-old female patient, primigravid, 36 weeks of gestation, without comorbidities, and diagnosed with severe pneumonia due to the SARS-CoV-2, showed rapid lung deterioration for which their pregnancy was interrupted by surgery. The patient was hospitalized in the Intensive Care Unit (ICU), connected to mechanical ventilation and receiving corticosteroids and antibiotics. The diagnosis of pulmonary fungal infection was made through bronchoalveolar lavage (BAL) culture, and the species identification was performed by sequencing of β-tubulin. Phylogenetic analysis with related species was performed for the confirmation of species identification. Antifungal susceptibility tests were performed for itraconazole (4 µg/mL), voriconazole (2 µg/mL), and amphotericin B (2 µg/mL). The patient was successfully treated with itraconazole. This is the second worldwide report of pulmonary infection by P. digitatum and the first in Chile. Although it is a fungus that rarely infects humans, it could represent an emerging opportunistic fungal pathogen, with associated risk factors that should be considered in the differential diagnosis of Penicillium species isolated from infections in humans. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

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16 pages, 913 KiB

Open AccessArticle

Challenges in Diagnosing COVID-19-Associated Pulmonary Aspergillosis in Critically Ill Patients: The Relationship between Case Definitions and Autoptic Data

by Giacomo Casalini, Andrea Giacomelli, Laura Galimberti, Riccardo Colombo, Elisabetta Ballone, Giacomo Pozza, Martina Zacheo, Miriam Galimberti, Letizia Oreni, Luca Carsana, Margherita Longo, Maria Rita Gismondo, Cristina Tonello, Manuela Nebuloni and Spinello Antinori

J. Fungi 2022, 8(9), 894; https://doi.org/10.3390/jof8090894 - 23 Aug 2022

Cited by 10 | Viewed by 1735

Abstract

Critically ill COVID-19 patients can develop invasive pulmonary aspergillosis (CAPA). Considering the weaknesses of diagnostic tests/case definitions, as well as the results from autoptic studies, there is a debate on the real burden of aspergillosis in COVID-19 patients. We performed a retrospective observational study on mechanically ventilated critically ill COVID-19 patients in an intensive care unit (ICU). The primary objective was to determine the burden of CAPA by comparing clinical diagnosis (through case definitions/diagnostic algorithms) with autopsy results. Twenty patients out of 168 (11.9%) developed probable CAPA. Seven (35%) were females, and the median age was 66 [IQR 59–72] years. Thirteen CAPA patients (65%) died and, for six, an autopsy was performed providing a proven diagnosis in four cases. Histopathology findings suggest a focal pattern, rather than invasive and diffuse fungal disease, in the context of prominent viral pneumonia. In a cohort of mechanically ventilated patients with probable CAPA, by performing a high rate of complete autopsies, invasive aspergillosis was not always proven. It is still not clear whether aspergillosis is the major driver of mortality in patients with CAPA. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

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Review

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10 pages, 286 KiB

Open AccessReview

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic

by Khee-Siang Chan, Chih-Cheng Lai, Wen-Liang Yu and Chien-Ming Chao

J. Fungi 2022, 8(10), 1111; https://doi.org/10.3390/jof8101111 - 21 Oct 2022

Cited by 5 | Viewed by 2004

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or secondary infection among patients with COVID-19. The possible co-pathogens include bacteria, viruses, and fungi, but COVID-19-associated cryptococcosis is rarely reported. This review provided updated and comprehensive information about this rare clinical entity of COVID-19-associated cryptococcosis. Through an updated literature search till 23 August 2022, we identified a total of 18 culture-confirmed case reports with detailed information. Half (n = 9) of them were elderly. Fifteen (83.3%) of them had severe COVID-19 and ever received systemic corticosteroid. Disseminated infection with cryptococcemia was the most common type of cryptococcosis, followed by pulmonary and meningitis. Except one case of C. laurentii, all other cases are by C. neoformans. Liposomal amphotericin B and fluconazole were the most commonly used antifungal agents. The overall mortality was 61.1% (11/18) and four of them did not receive antifungal agents before death. Improving the poor outcome requires a physician’s high suspicion, early diagnosis, and prompt treatment. Full article

(This article belongs to the Special Issue Fungal Infections in COVID-19 Patients)

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