Fungal Diseases and COVID-19

Overview

Symptoms of some fungal diseases can be similar to those of COVID-19, including fever, cough, and shortness of breath.1 Laboratory testing is necessary to determine if a person has a fungal infection or COVID-19. Some patients can have COVID-19 and a fungal infection at the same time.

People with severe COVID-19, such as those in an intensive care unit (ICU), are particularly vulnerable to bacterial and fungal infections. The most common fungal infections in patients with COVID-19 include aspergillosis or invasive candidiasis.16 These fungal co-infections are reported with increasing  frequency and can be associated with severe illness and  death.1,3,4,7,8 Awareness of the possibility of fungal co-infection is essential to reduce delays in diagnosis and treatment in order to help prevent severe illness and death from these infections.

COVID-19-associated pulmonary aspergillosis

Scientists are still learning about aspergillosis (infections caused by the fungus Aspergillus) in people with severe COVID-19. In the past, scientists thought aspergillosis occurred almost entirely in people with severely weakened immune systems. However, aspergillosis has been increasingly reported in patients without weakened immune systems but who have severe respiratory infections caused by viruses, including influenza. Several recent reports describe COVID-19-associated pulmonary aspergillosis (CAPA).1,3,6,9,10-14

Available information indicates that CAPA:

  • usually occurs in patients with severe COVID-19 (e.g., patients on ventilators in ICUs)1,6,11-14
  • can be difficult to diagnose because patients often have non-specific symptoms and testing typically requires a specimen from deep in the lungs11, 14
  • can cause severe illness and death8,9,11-14

Clinicians should consider the possibility of aspergillosis in patients with severe COVID-19 who have worsening respiratory function or sepsis, even if they  do not have classical risk factors for aspergillosis.16 Testing for CAPA usually involves obtaining specimens from patients’ lower respiratory tract, which are tested for Aspergillus galactomannan antigen and fungal culture.

Increased spread of Candida auris during COVID-19 pandemic

Candida auris is an emerging fungus that can cause outbreaks of severe infections in healthcare facilities. In the United States, it has most commonly spread in long-term care facilities caring for people with severe medical conditions. However, since the start of the COVID-19 pandemic, outbreaks of C. auris have been reported in COVID-19 units of acute care hospitals. These outbreaks may be related to changes in routine infection control practices during the COVID-19 pandemic, including limited availability of gloves and gowns, or reuse of these items, and changes in cleaning and disinfection practices. New C. auris cases without links to known cases or healthcare abroad have been identified recently in multiple states, suggesting an increase in undetected transmission. Screening for C. auris colonization, an important part of containment efforts, has been more limited as resources of healthcare facilities and health departments have been diverted to respond to COVID-19.

Invasive candidiasis in patients with COVID-19

Patients hospitalized for COVID-19 are at risk for healthcare-associated infections (HAIs), including candidemia, or bloodstream infections caused by Candida.7,1719 Fungal infections resistant to antifungal treatment have also been described in patients with severe COVID-19.19,20  Early diagnosis and monitoring for Candida infections and antifungal resistant infections (e.g., C. auris, azole-resistant Aspergillus) are key to reducing death from COVID-19 in patients with severe COVID-19 fungal co-infections.

Fungal pneumonias can resemble COVID-19

Other fungal diseases, such as Valley fever (coccidioidomycosis), histoplasmosis, and blastomycosis, can cause fever, cough, and shortness of breath, similar to COVID-19 and bacterial pneumonias.21 These fungi live in soil. People become infected by breathing in fungi present in the air. Clinicians should consider fungal pneumonias as a possible cause of respiratory illness, particularly if COVID-19 testing is negative. It is important to note that these fungal diseases can occur at the same time as COVID-19.22,23

COVID-19-associated mucormycosis

COVID-19–associated mucormycosis is less common than other COVID-19–associated fungal infections24, but emerging reports from India highlight the importance of considering this infection. Some medications used to treat severe COVID-19, including high-dose corticosteroids and tocilizumab, might predispose patients with COVID-19 to mucormycosis. Mucormycosis has been reported in patients with severe COVID-19 infection who lacked other classical mucormycosis risk factors, such as diabetes, conditions or medications that weaken the immune system, and cancer.25, 26
Early diagnosis and treatment are key to improving outcomes for patients with COVID-19–associated mucormycosis. Clinicians should consider the possibility of mucormycosis in patients with severe COVID-19 even when patients lack classical risk factors for this disease. Biomarkers for diagnosing invasive aspergillosis, such as beta-d-glucan and galactomannan, are typically negative in patients with mucormycosis. The treatment for mucormycosis frequently involves aggressive surgical intervention and treatment with antifungals, including amphotericin B, posaconazole, or isavuconazole. Voriconazole is not recommended for treating mucormycosis.27

References
  1. Hoenigl M. Invasive fungal disease complicating COVID-19: when it rains it poursexternal icon. Clin Infect Dis. 2020 Sep 5
  2. Garcia-Vidal C, Sanjuan G, Moreno-García E, et al. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort studyexternal icon. Clin Microbiol Infect. 2020 Jul 31
  3. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysisexternal icon. J Infect. 2020 May 27
  4. Gangneux JP, Bougnoux ME, Dannaoui E, Cornet M, Zahar JR. Invasive fungal diseases during COVID-19: We should be preparedexternal icon. J Mycol Med 2020 Jun
  5. Song G, Liang G, Liu W. Fungal co-infections associated with global COVID-19 pandemic: A clinical and diagnostic perspective from Chinaexternal icon. Mycopathologia. 2020 Jul 31
  6. Koehler P, Cornely OA, Böttiger BW, Dusse F, Eichenauer DA, Fuchs F, et al. COVID‐19 associated pulmonary aspergillosisexternal icon. Mycoses. 2020 May 15
  7. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive studyexternal icon. Lancet. 2020 Jan 30
  8. Beer KD, Jackson BR, Chiller T, Verweij PE, Van de Veerdonk FL, Wauters J. Does pulmonary aspergillosis complicate COVID-19?external icon Crit Care Exp. 2020 Sep 18
  9. Mohamed A, Rogers TR, Talento AF. COVID-19 associated invasive pulmonary aspergillosis: diagnostic and therapeutic challengesexternal icon. J Fungi. 2020 Jul 22
  10. Verweij PE, Gangneu J, Bassetti M, Bruggemann RJM, Cornely OA, Koehler P, et al. Diagnosing COVID-19-associated pulmonary aspergillosisexternal icon. Lancet Microbe. 2020 May 10
  11. Koehler P, Bassetti M, Chakrabarti A, Chen SCA, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidanceexternal icon. Lancet. 2020 Dec 14
  12. Dellière S, Dudoignon E, Fodil S, Voicu S, Collet M, Oillic P, et al. Risk factors associated with Covid-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohortexternal icon. Clin Microbiol Infect. 2020 Dec 13
  13. Marr KA, Platt A, Tornheim JA, Zhang SX, Datta K, Cardozo C, et al. Aspergillosis complicating severe coronavirus disease. Emerg Infect Dis. 2021 Jan
  14. Benedetti MF, Alava KH, Sagardia J, et al. COVID-19 associated pulmonary aspergillosis in ICU patients: Report of five cases from Argentinaexternal icon. Med Mycol Case Rep. 2020 Dec 7
  15. Arastehfar A, Carvalho A, van de Veerdonk, FL, Jenks JD, Koelher P, Krause R, et al. COVID-19 associated pulmonary aspergillosis (CAPA) – from immunology to treatmentexternal icon. 2020 Jun 24
  16. CDC: Information for Healthcare Professionals About Aspergillosis
  17. Nucci M, Barreiros G, Guimarães LF, Deriquehem VA, Castiñeiras AC, Nouér SA. Increased incidence of candidemia in a tertiary care hospital with the Covid‐19 pandemicexternal icon. Mycoses. 2020 Dec 4
  18. Hughes S, Troise O, Mughal N, Moorse LSP. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care settingexternal icon. Clin Microbiol Infect. 2020 Jun 27
  19. Posteraro B, Torelli R, Vella A, Leone PM, De Angelis G, De Carolis E, et al. Pan-echinocandin-resistant Candida glabratabloodstream infection complicating COVID-19: a fatal case reportexternal icon. J Fungi. 2020 Sep 6
  20. Meijer EFJ, Dofferhoff ASM, Hoiting O, Buil JB, Meis JF. Azole-resistant COVID-19-associated pulmonary aspergillosis in an immunocompetent host: a case reportexternal icon. J Fungi. 2020 Jun 6
  21. Benedict K, Kobayashi M, Garg S, Chiller T, Jackson BR. Symptoms in blastomycosis, coccidioidomycosis, and histoplasmosis versus other respiratory illnesses in commercially insured adult outpatients, United States, 2016–2017external icon. Clin Infect Dis. 2020 Oct 16
  22. Shah AS, Heidari A, Civelli VF, Sharma R, Clark CS, Munoz AD, et al. The coincidence of 2 epidemics, coccidioidomycosis and SARS-CoV-2: a case reportexternal icon. J Investig Med High Impact Case Rep. 2020 Jun 4
  23. Bertolini M, Mutti MF, Barletta JA, et al. COVID-19 associated with AIDS-related disseminated histoplasmosis: a case reportexternal icon. Int J STD AIDS. 2020 Sep 9
  24. Rabagliati R, Rodríguez N, Núñez C, Huete A, Bravo S, Garcia P. COVID-19-Associated Mold Infection in Critically Ill Patients, Chile. Emerging infectious diseases. 2021 May
  25. Garg D, Muthu V, Sehgal IS, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literatureexternal icon. Mycopathologia. 2021 Feb 5
  26. Kanwar A, Jordan A, Olewiler S, Wehberg K, Cortes M, Jackson BR. A Fatal Case of Rhizopus azygosporus Pneumonia Following COVID-19external icon. Journal of Fungi. 2021 Feb 28
  27. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortiumexternal icon. The Lancet Infectious diseases. 2019 Nov 4