COVID-19 and fungal infection: the need for a strategic approach
Authors: P Lewis White, Rishi Dhillon, Harriet Hughes, Matthew P Wise, Matthijs Backx
Journal: The Lancet Microbe (2020)

We read with interest the Correspondence from Katie Heard and colleagues1Heard KL Hughes S Mughal N Moor LSP COVID-19 and fungal superinfection.Lancet Microbe. 2020; 1: e107Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar describing the absence of diagnostically confirmed COVID-19-associated pulmonary aspergillosis (CAPA) in patients who are critically ill and commend the authors for considering this potential superinfection. It is evident from their approach that empirical antifungal therapy does not seem to be beneficial. Five (21%) patients who received empirical antifungals had adverse effects and there were no cases of CAPA documented; therefore, this approach could increase patient morbidity without providing a survival benefit. The administration of antifungals before diagnostic testing has been shown to limit the performance of fungal biomarker testing; therefore, an empirical strategy could also limit the ability to make a definitive diagnosis and subsequently target antifungal therapy effectively.2Marr KA Laverdiere M Gugel A Leisenring W Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay.Clin Infect Dis. 2005; 40: 1762-1769Crossref PubMed Scopus (394) Google Scholar Empirical antifungal therapy was first administered almost 50 years ago for treatment of haematology patients at high risk of developing invasive fungal disease, nowadays, with the availability of non-culture diagnostics, the justification for its use in critical care is unclear. There is, therefore, a need for a strategic approach for the diagnosis and subsequent management of CAPA.3Gangneux JP Bougnoux ME Dannaoui E Cornet M Zahar JR Invasive fungal diseases during COVID-19: we should be prepared.J Mycol Med. 2020; 30100971Crossref PubMed Scopus (230) Google Scholar In July, 2020, an algorithm was proposed involving the stratified testing of serological and respiratory samples to enhance the diagnosis of CAPA, and included interpretation for the initiation of antifungal therapy.4Armstrong-James D Youngs J Bicanic T et al.Confronting and mitigating the risk of COVID-19 associated pulmonary aspergillosis (CAPA).Eur Respir J. 2020; (published online July 23.)https://doi.org/10.1183/13993003.02554-2020Crossref PubMed Scopus (89) Google Scholar In line with this algorithm, a diagnostic strategy to enhance the detection of CAPA across all intensive care units (ICU) was implemented in Wales and substantial rates of CAPA were documented in 19 (14%) of 135 patients with COVID-19 confirmed by PCR.5White PL Dhillon R Cordey A et al.A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU.SSRN. 2020; (published online July 14.) (preprint)https://papers.ssrn.com/abstract=3644400Crossref Google Scholar We also noted increased rates of invasive yeast infections (17 of 135 [13%]) and support the suggestion of Heard and colleagues1Heard KL Hughes S Mughal N Moor LSP COVID-19 and fungal superinfection.Lancet Microbe. 2020; 1: e107Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar for further research into Candida spp as a potential COVID-19-associated superinfection.5White PL Dhillon R Cordey A et al.A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU.SSRN. 2020; (published online July 14.) (preprint)https://papers.ssrn.com/abstract=3644400Crossref Google Scholar Invasive fungal infection in our patients was associated with increased ICU admission (median 7 days) and statistically significant mortality (19 of 36 [53%]), but this could be negated by the use of appropriate antifungal therapy.5White PL Dhillon R Cordey A et al.A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU.SSRN. 2020; (published online July 14.) (preprint)https://papers.ssrn.com/abstract=3644400Crossref Google Scholar Treating patients with suspected Aspergillus spp in the respiratory tract or circulation in the absence of proven disease is not perfect; however, it is surely an advance over empirical therapy that can have adverse effects, potentially limiting diagnostic accuracy, and treats non-specific symptoms associated with patients with COVID-19 who are critically ill. The incorporation of a strategic diagnostic algorithm is crucial for identifying invasive fungal disease in patients with COVID-19 who require critical-care management and should be done frequently (weekly) throughout the period of severe respiratory distress. PLW has done diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics, received speakers fees, expert advice fees, and meeting sponsorship from Gilead, speaker and expert advice fees from F2G, speaker fees from MSD and Pfizer, and is a founding member of the European Aspergillus PCR Initiative. MB has received speakers fees, expert advice fees, and meeting sponsorship from Gilead and Abbvie. RD has received educational grants from Gilead, Eumedica, Astellas Pharma, TevaPharmaceutical Industries, MSD, and Chiesi. All other authors declare no competing interests. COVID-19 and fungal superinfection