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15 pages, 3402 KiB

Open AccessArticle

Diagnostic Performance and Clinical Utility of Conventional PCR Assay in Early Diagnosis of COVID-19 Associated Rhino-Orbito-Cerebral Mucormycosis

by Samir Mohapatra, Manas Ranjan Barik, Suryasnata Rath, Savitri Sharma, Archisman Mohapatra, Sharmistha Behera, Souvagini Acharya, Dipti Ranjan Pattjoshi, Rajesh Kumar Padhi and Himansu Sekhar Behera

J. Fungi 2022, 8(8), 844; https://doi.org/10.3390/jof8080844 - 11 Aug 2022

Cited by 3 | Viewed by 2219

Abstract

Early diagnosis and treatment of rhino-orbital-cerebral mucormycosis (ROCM) are crucial. Potassium hydroxide with Calcofluorwhite (KOH + CFW) smears can demonstrate the fungal hyphae, but mixed infections caused by both mucorales and non-mucorales pose a diagnostic challenge. Polymerase chain reaction (PCR) can detect mixed [...] Read more.

Early diagnosis and treatment of rhino-orbital-cerebral mucormycosis (ROCM) are crucial. Potassium hydroxide with Calcofluorwhite (KOH + CFW) smears can demonstrate the fungal hyphae, but mixed infections caused by both mucorales and non-mucorales pose a diagnostic challenge. Polymerase chain reaction (PCR) can detect mixed infections and differentiate mucorales from non-mucorales. This study aimed to evaluate the utility of a single reaction PCR in the diagnosis of ROCM and the efficacy of nasal biopsy and endonasal swab in the detection of fungus. Sixty-six clinical samples were collected from 33 patients and were subjected to KOH + CFW smear, culture and PCR. PCR was performed using pan-fungal primers targeting the 28S large subunit rRNA gene, and the amplified products were further sequenced to identify the fungi. KOH + CFW smear, culture and PCR detected mucorales in 54.6%, 27.3% and 63.6% patients, respectively. PCR detected mixed infection in 51.5% patients compared to 9.1% by KOH + CFW smear. PCR detected fungus in 90% of nasal biopsies and 77.8% of endonasal swabs. Rhizopus spp. was the most common fungi identified in 43.2% of PCR-positive samples. PCR is effective in detecting mixed infection and in the diagnosis of ROCM. Nasal biopsies had better fungal detection rates than endonasal swabs. Full article

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

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16 pages, 2369 KiB

Open AccessArticle

Development of a Monoclonal Antibody and a Serodiagnostic Lateral-Flow Device Specific to Rhizopus arrhizus (Syn. R. oryzae), the Principal Global Agent of Mucormycosis in Humans

by Genna E. Davies and Christopher R. Thornton

J. Fungi 2022, 8(7), 756; https://doi.org/10.3390/jof8070756 - 21 Jul 2022

Cited by 18 | Viewed by 6303

Abstract

Mucormycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. Though a number of different species can cause mucormycosis, the principal agent of the disease worldwide is Rhizopus arrhizus, which accounts for the majority of [...] Read more.

Mucormycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. Though a number of different species can cause mucormycosis, the principal agent of the disease worldwide is Rhizopus arrhizus, which accounts for the majority of rhino-orbital-cerebral, pulmonary, and disseminated infections in immunocompromised individuals. It is also the main cause of life-threatening infections in patients with poorly controlled diabetes mellitus, and in corticosteroid-treated patients with SARS-CoV-2 infection, where it causes the newly described disease, COVID-19-associated mucormycosis (CAM). Diagnosis currently relies on non-specific CT, a lengthy and insensitive culture from invasive biopsy, and a time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests for the disease that detect biomarkers of infection, and which allow point-of-care diagnosis. Here, we report the development of an IgG1 monoclonal antibody (mAb), KC9, which is specific to Rhizopus arrhizus var. arrhizus (syn. Rhizopus oryzae) and Rhizopus arrhizus var. delemar (Rhizopus delemar), and which binds to a 15 kDa extracellular polysaccharide (EPS) antigen secreted during hyphal growth of the pathogen. Using the mAb, we have developed a competitive lateral-flow device (LFD) that allows rapid (30 min) and sensitive (~50 ng/mL running buffer) detection of the EPS biomarker, and which is compatible with human serum (limit of detection of ~500 ng/mL) and bronchoalveolar lavage fluid (limit of detection of ~100 ng/mL). The LFD, therefore, provides a potential novel opportunity for the non-invasive detection of mucormycosis caused by Rhizopus arrhizus. Full article

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

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12 pages, 602 KiB

Open AccessArticle

Impact of the COVID-19 Pandemic on the Clinical Profile of Candidemia and the Incidence of Fungemia Due to Fluconazole-Resistant Candida parapsilosis

by Antonio Ramos-Martínez, Ilduara Pintos-Pascual, Jesús Guinea, Andrea Gutiérrez-Villanueva, Edith Gutiérrez-Abreu, Judith Díaz-García, Ángel Asensio, Reyes Iranzo, Isabel Sánchez-Romero, María Muñoz-Algarra, Víctor Moreno-Torres, Jorge Calderón-Parra, Elena Múñez and Ana Fernández-Cruz

J. Fungi 2022, 8(5), 451; https://doi.org/10.3390/jof8050451 - 27 Apr 2022

Cited by 31 | Viewed by 3153

Abstract

Severely ill COVID-19 patients are at high risk of nosocomial infections. The aim of the study was to describe the characteristics of candidemia during the pre-pandemic period (January 2019–February 2020) compared to the pandemic period (March 2020–September 2021). Antifungal susceptibilities were assessed using [...] Read more.

Severely ill COVID-19 patients are at high risk of nosocomial infections. The aim of the study was to describe the characteristics of candidemia during the pre-pandemic period (January 2019–February 2020) compared to the pandemic period (March 2020–September 2021). Antifungal susceptibilities were assessed using the EUCAST E.Def 7.3.2 broth dilution method. Fluconazole-resistant C. parapsilosis isolates (FRCP) were studied for sequencing of the ERG11 gene. The incidence of candidemia and C. parapsilosis bloodstream infection increased significantly in the pandemic period (p = 0.021). ICU admission, mechanical ventilation, parenteral nutrition and corticosteroids administration were more frequent in patients with candidemia who had been admitted due to COVID-19. Fifteen cases of FRCP fungemia were detected. The first case was recorded 10 months before the pandemic in a patient transferred from another hospital. The incidence of FRCP in patients admitted for COVID-19 was 1.34 and 0.16 in all other patients (p < 0.001). ICU admission, previous Candida spp. colonization, arterial catheter use, parenteral nutrition and renal function replacement therapy were more frequent in patients with candidemia due to FRCP. All FRCP isolates showed the Y132F mutation. In conclusion, the incidence of candidemia experienced an increase during the COVID-19 pandemic and FRCP fungemia was more frequent in patients admitted due to COVID-19. Full article

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

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13 pages, 722 KiB

Open AccessArticle

COVID-19 Associated Pulmonary Aspergillosis (CAPA): Hospital or Home Environment as a Source of Life-Threatening Aspergillus fumigatus Infection?

by Teresa Peláez-García de la Rasilla, Irene González-Jiménez, Andrea Fernández-Arroyo, Alejandra Roldán, Jose Luis Carretero-Ares, Marta García-Clemente, Mauricio Telenti-Asensio, Emilio García-Prieto, Mar Martínez-Suarez, Fernando Vázquez-Valdés, Santiago Melón-García, Luis Caminal-Montero, Inmaculada Fernández-Simón, Emilia Mellado and María Luisa Sánchez-Núñez

J. Fungi 2022, 8(3), 316; https://doi.org/10.3390/jof8030316 - 19 Mar 2022

Cited by 13 | Viewed by 3739

Abstract

Most cases of invasive aspergillosis are caused by Aspergillus fumigatus, whose conidia are ubiquitous in the environment. Additionally, in indoor environments, such as houses or hospitals, conidia are frequently detected too. Hospital-acquired aspergillosis is usually associated with airborne fungal contamination of the [...] Read more.

Most cases of invasive aspergillosis are caused by Aspergillus fumigatus, whose conidia are ubiquitous in the environment. Additionally, in indoor environments, such as houses or hospitals, conidia are frequently detected too. Hospital-acquired aspergillosis is usually associated with airborne fungal contamination of the hospital air, especially after building construction events. A. fumigatus strain typing can fulfill many needs both in clinical settings and otherwise. The high incidence of aspergillosis in COVID patients from our hospital, made us wonder if they were hospital-acquired aspergillosis. The purpose of this study was to evaluate whether the hospital environment was the source of aspergillosis infection in CAPA patients, admitted to the Hospital Universitario Central de Asturias, during the first and second wave of the COVID-19 pandemic, or whether it was community-acquired aspergillosis before admission. During 2020, sixty-nine A. fumigatus strains were collected for this study: 59 were clinical isolates from 28 COVID-19 patients, and 10 strains were environmentally isolated from seven hospital rooms and intensive care units. A diagnosis of pulmonary aspergillosis was based on the ECCM/ISHAM criteria. Strains were genotyped by PCR amplification and sequencing of a panel of four hypervariable tandem repeats within exons of surface protein coding genes (TRESPERG). A total of seven genotypes among the 10 environmental strains and 28 genotypes among the 59 clinical strains were identified. Genotyping revealed that only one environmental A. fumigatus from UCI 5 (box 54) isolated in October (30 October 2020) and one A. fumigatus isolated from a COVID-19 patient admitted in Pneumology (Room 532-B) in November (24 November 2020) had the same genotype, but there was a significant difference in time and location. There was also no relationship in time and location between similar A. fumigatus genotypes of patients. The global A. fumigatus, environmental and clinical isolates, showed a wide diversity of genotypes. To our knowledge, this is the first study monitoring and genotyping A. fumigatus isolates obtained from hospital air and COVID-19 patients, admitted with aspergillosis, during one year. Our work shows that patients do not acquire A. fumigatus in the hospital. This proves that COVID-associated aspergillosis in our hospital is not a nosocomial infection, but supports the hypothesis of “community aspergillosis” acquisition outside the hospital, having the home environment (pandemic period at home) as the main suspected focus of infection. Full article

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

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14 pages, 577 KiB

Open AccessArticle

Incidence of Candidemia Is Higher in COVID-19 versus Non-COVID-19 Patients, but Not Driven by Intrahospital Transmission

by Marina Machado, Agustín Estévez, Carlos Sánchez-Carrillo, Jesús Guinea, Pilar Escribano, Roberto Alonso, Maricela Valerio, Belén Padilla, Emilio Bouza and Patricia Muñoz

J. Fungi 2022, 8(3), 305; https://doi.org/10.3390/jof8030305 - 16 Mar 2022

Cited by 37 | Viewed by 3679

Abstract

There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared [...] Read more.

There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all C. albicans, C. parapsilosis, and C. tropicalis isolates (n = 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient Candida transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission. Full article

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

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7 pages, 545 KiB

Open AccessArticle

Risk Factors for COVID-19 Associated Mucormycosis: The Ophthalmologist’s Perspective

by Alper Bilgic, Laurent Kodjikian, Aditya Sudhalkar, Shyamal Dwivedi, Viraj Vasavada, Arpan Shah, Mikhail Dziadzko and Thibaud Mathis

J. Fungi 2022, 8(3), 271; https://doi.org/10.3390/jof8030271 - 8 Mar 2022

Cited by 5 | Viewed by 4079

Abstract

The COVID-19 pandemic has led to a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis (ROCM) in India. The purpose of our report is to describe the prevalence of ROCM in the context of SARS-CoV-2 infection during the second Indian COVID-19 wave, as [...] Read more.

The COVID-19 pandemic has led to a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis (ROCM) in India. The purpose of our report is to describe the prevalence of ROCM in the context of SARS-CoV-2 infection during the second Indian COVID-19 wave, as well as its diagnostics proceeding, and to discuss the challenges met in the time frame from the suspected diagnosis to the therapeutic decision in such patients. We conducted a retrospective multicentre case series study at six centres of Sudhalkar and Raghudeep group of hospitals in India. ROCM was confirmed in 38 (2.5%) of the 1546 patients admitted with SARS-CoV-2 infection. The average time to establish a diagnosis was 16 days. In total, 19 (50%) patients suffered from type 2 diabetes and were mostly treated with hypoglycaemic agents (in 90% of cases). The standard of care for SARS-CoV-2 management included systemic steroids therapy, intravenous remdesivir for 5 days, and concomitant prophylactic antibiotic therapy following admission. The median (IQR) blood glucose levels in all patients during the course of hospitalisation was 320 (250.5–375) mg/dl. A total of 16% of patients had an irreparable functional loss, and the mortality was 5%. We may hypothesise that excessive administration of antibiotics that profoundly affects human microbiota, coupled with poorly controlled glycaemia and unprotocolised haphazard steroid administration, contribute to a favourable setting for mucormycosis infections. Full article

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

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11 pages, 847 KiB

Open AccessArticle

Association of COVID-19-Associated Pulmonary Aspergillosis with Cytomegalovirus Replication: A Case–Control Study

by Jorge Calderón-Parra, Victor Moreno-Torres, Patricia Mills-Sanchez, Sandra Tejado-Bravo, Isabel Romero-Sánchez, Bárbara Balandin-Moreno, Marina Calvo-Salvador, Francisca Portero-Azorín, Sarela García-Masedo, Elena Muñez-Rubio, Antonio Ramos-Martinez and Ana Fernández-Cruz

J. Fungi 2022, 8(2), 161; https://doi.org/10.3390/jof8020161 - 6 Feb 2022

Cited by 8 | Viewed by 2555

Abstract

Introduction: Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. However, its association with COVID-19-associated pulmonary aspergillosis (CAPA) has not been described. We aimed to examine the possible link between CMV replication and CAPA occurrence. Methods: A single-center, [...] Read more.

Introduction: Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. However, its association with COVID-19-associated pulmonary aspergillosis (CAPA) has not been described. We aimed to examine the possible link between CMV replication and CAPA occurrence. Methods: A single-center, retrospective case–control study was conducted. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. Two controls were selected for each case among critically ill COVID-19 patients. Results: In total, 24 CAPA cases were included, comprising 14 possible CAPA and 10 probable CAPA. Additionally, 48 matched controls were selected. CMV replication was detected more frequently in CAPA than in controls (75.0% vs. 35.4%, p = 0.002). Probable CMV end-organ disease was more prevalent in CAPA (20.8% vs. 4.2%, p = 0.037). After adjusting for possible confounding factors, CMV replication persisted strongly associated with CAPA (OR 8.28 95% CI 1.90–36.13, p = 0.005). Among 11 CAPA cases with CMV PCR available prior to CAPA, in 9 (81.8%) cases, CMV replication was observed prior to CAPA diagnosis. Conclusions: Among critically ill COVID-19 patients, CMV replication was associated with CAPA and could potentially be considered a harbinger of CAPA. Further studies are needed to confirm this association. Full article

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

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10 pages, 853 KiB

Open AccessArticle

COVID-19-Associated Pulmonary Aspergillosis: A Single-Center Experience in Central Valley, California, January 2020–March 2021

by Geetha Sivasubramanian, Hebah Ghanem, Michele Maison-Fomotar, Ratnali Jain and Robert Libke

J. Fungi 2021, 7(11), 948; https://doi.org/10.3390/jof7110948 - 10 Nov 2021

Cited by 7 | Viewed by 2645

Abstract

Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center′s [...] Read more.

Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center′s intensive care units between January 2020 and March 2021, who also had respiratory cultures positive for Aspergillus species. Among a large cohort of 970 patients admitted to the ICU with severe COVID-19 infections during our study period, 48 patients had Aspergillus species growing in respiratory cultures. Based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, 2 patients in the study had proven CAPA, 9 had probable CAPA, and 37 had possible CAPA. The incidence of CAPA was 5%. The mean duration from a positive COVID-19 test to Aspergillus spp. being recovered from the respiratory cultures was 16 days, and more than half of the patients had preceding fever or worsening respiratory failure despite adequate support and management. Antifungals were given for treatment in 44% of the patients for a mean duration of 13 days. The overall mortality rate in our study population was extremely high with death occurring in 40/48 patients (83%). Full article

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

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Review

Jump to: Research

21 pages, 354 KiB

Open AccessReview

Isavuconazole for COVID-19-Associated Invasive Mold Infections

by Nadir Ullah, Chiara Sepulcri and Malgorzata Mikulska

J. Fungi 2022, 8(7), 674; https://doi.org/10.3390/jof8070674 - 28 Jun 2022

Cited by 8 | Viewed by 3392

Abstract

Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated [...] Read more.

Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated aspergillosis (CAPA), and COVID-19-associated mucormycosis (CAM). Among all studies which reported treatment of CAPA, approximately 10% of patients were reportedly treated with isavuconazole. Considering 14 identified studies that reported the use of isavuconazole for CAPA, isavuconazole was used in 40% of patients (95 of 235 treated patients), being first-line monotherapy in over half of them. We identified six studies that reported isavuconazole use in CAM, either alone or in combination therapy. Overall, isavuconazole was used as therapy in 13% of treated CAM patients, frequently as combination or sequential therapy. The use of isavuconazole in CAPA and CAM is complicated by the challenge of achieving adequate exposure in COVID-19 patients who are frequently obese and hospitalized in the ICU with concomitant renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO). The presence of data on high efficacy in the treatment of aspergillosis, lower potential for drug–drug interactions (DDIs) and for subtherapeutic levels, and no risk of QT prolongation compared to other mold-active azoles, better safety profile than voriconazole, and the possibility of using an intravenous formulation in the case of renal failure are the advantages of using isavuconazole in this setting. Full article

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

15 pages, 320 KiB

Open AccessReview

Concurrent Infection with SARS-CoV-2 and Pneumocystis jirovecii in Immunocompromised and Immunocompetent Individuals

by Francesca Gioia, Hanan Albasata and Seyed M. Hosseini-Moghaddam

J. Fungi 2022, 8(6), 585; https://doi.org/10.3390/jof8060585 - 30 May 2022

Cited by 7 | Viewed by 2675

Abstract

Coronavirus disease 2019 (COVID-19) may occur with concurrent infections caused by bacterial and fungal microorganisms. This systematic review evaluated studies reporting concomitant COVID-19 and Pneumocystis jirovecii pneumonia (PJP). We found 39 patients (74% male, median age: 56.8 (range: 11–83) years), including 66% immunosuppressed [...] Read more.

Coronavirus disease 2019 (COVID-19) may occur with concurrent infections caused by bacterial and fungal microorganisms. This systematic review evaluated studies reporting concomitant COVID-19 and Pneumocystis jirovecii pneumonia (PJP). We found 39 patients (74% male, median age: 56.8 (range: 11–83) years), including 66% immunosuppressed individuals (23% HIV-infected and 41% on long-term corticosteroid therapy). Patients were characteristically severely ill (mechanical ventilation: 70%), associated with 41% mortality. The median lymphocyte count was 527 cells/mm³ (range: 110–2200), and the median CD4+ T cell count was 206 cells/mm³ (range: 8–1021). We identified three patterns of concurrent COVID-19 and P. jirovecii infection. The first pattern (airway colonization with a low burden of P. jirovecii) does not seem to modify the COVID-19 course of illness. However, P. jirovecii superinfection, typically occurring weeks after COVID-19 diagnosis as a biphasic illness, and P. jirovecii coinfection characteristically results in progressive multilobar pneumonia, which is associated with poor outcomes. To support this categorization, we reported three patients with concurrent PJP and COVID-19 identified in our institution, presenting these clinical scenarios. The diagnosis of PJP requires a high index of suspicion, since clinical and radiological characteristics overlap with COVID-19. Observational studies are necessary to determine the PJP burden in patients with COVID-19 requiring hospitalization. Full article

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

36 pages, 2898 KiB

Open AccessReview

Dental and Oral Manifestations of COVID-19 Related Mucormycosis: Diagnoses, Management Strategies and Outcomes

by Omer Sefvan Janjua, Muhammad Saad Shaikh, Muhammad Amber Fareed, Sana Mehmood Qureshi, Muhammad Ikram Khan, Danya Hashem and Muhammad Sohail Zafar

J. Fungi 2022, 8(1), 44; https://doi.org/10.3390/jof8010044 - 31 Dec 2021

Cited by 24 | Viewed by 5889

Abstract

It has been nearly two years since the pandemic caused by the novel coronavirus disease (COVID-19) has affected the world. Several innovations and discoveries related to COVID-19 are surfacing every day and new problems associated with the COVID-19 virus are also coming to [...] Read more.

It has been nearly two years since the pandemic caused by the novel coronavirus disease (COVID-19) has affected the world. Several innovations and discoveries related to COVID-19 are surfacing every day and new problems associated with the COVID-19 virus are also coming to light. A similar situation is with the emergence of deep invasive fungal infections associated with severe acute respiratory syndrome 2 (SARS-CoV-2). Recent literature reported the cases of pulmonary and rhino-cerebral fungal infections appearing in patients previously infected by COVID-19. Histopathological analysis of these cases has shown that most of such infections are diagnosed as mucormycosis or aspergillosis. Rhino-orbital-cerebral mucormycosis usually affects the maxillary sinus with involvement of maxillary teeth, orbits, and ethmoidal sinuses. Diabetes mellitus is an independent risk factor for both COVID-19 as well as mucormycosis. At this point, there is scanty data on the subject and most of the published literature comprises of either case reports or case series with no long-term data available. The aim of this review paper is to present the characteristics of COVID-19 related mucormycosis and associated clinical features, outcome, diagnostic and management strategies. A prompt diagnosis and aggressive treatment planning can surely benefit these patients. Full article

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

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33 pages, 491 KiB

Open AccessReview

Invasive Fungal Infections Complicating COVID-19: A Narrative Review

by Giacomo Casalini, Andrea Giacomelli, Annalisa Ridolfo, Cristina Gervasoni and Spinello Antinori

J. Fungi 2021, 7(11), 921; https://doi.org/10.3390/jof7110921 - 29 Oct 2021

Cited by 73 | Viewed by 5486

Abstract

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 [...] Read more.

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium. Full article

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

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