COVID-19-associated fungal infections

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Abstract

Coronavirus disease 2019 (COVID-19)-associated invasive fungal infections are an important complication in a substantial number of critically ill, hospitalized patients with COVID-19. Three groups of fungal pathogens cause co-infections in COVID-19: Aspergillus, Mucorales and Candida species, including Candida auris. Here we review the incidence of COVID-19-associated invasive fungal infections caused by these fungi in low-, middle- and high-income countries. By evaluating the epidemiology, clinical risk factors, predisposing features of the host environment and immunological mechanisms that underlie the pathogenesis of these co-infections, we set the scene for future research and development of clinical guidance.

Abstract

Hoenigl and colleagues review the epidemiology, immunology and clinical risk factors contributing to COVID-19-associated fungal infections.

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Most cited references 161

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Nanshan Chen, Min Zhou, Xuan Dong … (2022)

Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.

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Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Xiaobo Yang, Yuan Yu, Jiqian Xu … (2020)

Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.

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Author and article information

Contributors

Martin Hoenigl:

ORCID: http://orcid.org/0000-0002-1653-2824

hoeniglmartin@gmail.com

Agostinho Carvalho:

ORCID: http://orcid.org/0000-0001-8935-8030

agostinhocarvalho@med.uminho.pt

Journal

Journal ID (nlm-ta): Nat Microbiol

Journal ID (iso-abbrev): Nat Microbiol

Title: Nature Microbiology

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2058-5276

Publication date (Electronic): 2 August 2022

Publication date (Print): 2022

Volume: 7

Issue: 8

Pages: 1127-1140

Affiliations

[1 ]GRID grid.11598.34, ISNI 0000 0000 8988 2476, Division of Infectious Diseases, Department of Internal Medicine, , Medical University of Graz, ; Graz, Austria

[2 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Division of Infectious Diseases and Global Public Health, Department of Medicine, , University of California San Diego, ; La Jolla, CA USA

[3 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Clinical and Translational Fungal Working Group, , University of California San Diego, ; La Jolla, CA USA

[4 ]GRID grid.6190.e, ISNI 0000 0000 8580 3777, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Chair Translational Research, , Faculty of Medicine and University Hospital Cologne, University of Cologne, ; Cologne, Germany

[5 ]GRID grid.6190.e, ISNI 0000 0000 8580 3777, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), , Faculty of Medicine and University Hospital Cologne, University of Cologne, ; Cologne, Germany

[6 ]GRID grid.10328.38, ISNI 0000 0001 2159 175X, Life and Health Sciences Research Institute (ICVS), School of Medicine, , University of Minho, ; Braga, Portugal

[7 ]GRID grid.10328.38, ISNI 0000 0001 2159 175X, ICVS/3B’s-PT Government Associate Laboratory, ; Braga/Guimarães, Portugal

[8 ]GRID grid.6190.e, ISNI 0000 0000 8580 3777, Department I of Internal Medicine, , University of Cologne, ; Cologne, Germany

[9 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, , Universidade de São Paulo, ; São Paulo, Brazil

[10 ]GRID grid.239844.0, ISNI 0000 0001 0157 6501, Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation, , Harbor-University of California at Los Angeles Medical Center, ; Torrance, CA USA

[11 ]GRID grid.19006.3e, ISNI 0000 0000 9632 6718, David Geffen School of Medicine at University of California Los Angeles, ; Los Angeles, CA USA

Author information

Martin Hoenigl http://orcid.org/0000-0002-1653-2824

Rosanne Sprute http://orcid.org/0000-0003-2457-6437

Cristina Cunha http://orcid.org/0000-0002-6002-5782

Matteo Oliverio http://orcid.org/0000-0002-7969-2796

Gustavo H. Goldman http://orcid.org/0000-0002-2986-350X

Ashraf S. Ibrahim http://orcid.org/0000-0003-3787-8530

Agostinho Carvalho http://orcid.org/0000-0001-8935-8030

Article

Publisher ID: 1172

DOI: 10.1038/s41564-022-01172-2

PMC ID: 9362108

PubMed ID: 35918423

SO-VID: 198ad59c-65ba-4668-ba5e-bb13a7094cd5

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date received : 18 November 2021

Date accepted : 13 June 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100005856, NOVA | Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa (FCT/UNL);

Award ID: PTDC/SAU-SER/29635/2017

Award ID: UIDB/50026/2020 and UIDP/50026/2020

Award Recipient : Cristina Cunha Agostinho Carvalho

Funded by: FundRef https://doi.org/10.13039/100000060, U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID);

Award ID: R01AI153356

Award ID: R01AI063503

Award Recipient : Gustavo H. Goldman Ashraf S. Ibrahim

Funded by: FundRef https://doi.org/10.13039/100010661, EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020);

Award ID: no. 847507

Award Recipient : Agostinho Carvalho