key: cord-0932846-11meaau3
authors: White, P Lewis; Dhillon, Rishi; Healy, Brendan; Wise, Matthew P; Backs, Matthijs
title: Candidaemia in COVID-19, a link to disease pathology or increased clinical pressures?
date: 2020-10-18
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa1597
sha: eaed3fecadba80b2e8fee6e17332bf9a03380b80
doc_id: 932846
cord_uid: 11meaau3

nan

M a n u s c r i p t 2 Dear Editor:

With UK reports describing a significant incidence of invasive candidal disease (IC) in critically-ill COVID-19 patients, we were intrigued to see that other countries, heavily affected by the COVID-19 pandemic, were also documenting this secondary complication. [1] [2] [3] [4] [5] Mastrangelo and colleagues correctly highlighted that we did not indicate whether the incidence of IC in our primary COVID-19 study was higher than the non-COVID-19 population. [1, 3] Their study confirmed that IC incidence was increased in COVID-19 patients, linked to intensive care management and the use of immunosuppressive agents. Our study only involved critical-care patients, the use of the immunomodulatory therapies was not widely documented and no significant risks for developing IC were identified. [1] In response to Mastrangelo and colleagues, the incidence of IC in non-COVID-19 and COVID-19 critically-ill patients was compared. Analysis of two non-COVID-19 populations was undertaken, In the Pre-COVID-19 population 2/157 (1.3%) patients had a documented invasive yeast infection (Table 1 ), similar to rates typically seen in UK critical-care units (<1%). [6] A further six line infections were documented, generating a combined IC rate of 5.1% (95% CI: 2.6-9.7). During the first wave of COVID-19 in Wales there were 12 (6.6%, 95% CI: 3.8-11.1) documented fungaemias and 12 A c c e p t e d M a n u s c r i p t 3 Our current understanding of the host's immune dysfunction due to COVID-19 leads to the hypothesis that it is not a major factor in IC. [5] While, hyper-inflammatory disruption of respiratory mucosal membranes does provide the opportunity for commensal Candida to become invasive, our data suggests that the increased IC rates during COVID-19 are not directly associated with the disease itself. Other factors, including classical clinical risk factors (e.g. Central lines, antibiotics etc.), sepsis enhanced translocation of gut microbiota, a switch in the composition of microbiota promoting commensal/colonizing Candida or altered practice during the pandemic warrant further investigation. [3, 5] The necessity for extracorporeal membrane oxygenation (ECMO) and the use of corticosteroids in COVID-19 have been suggested as specific risk factors, but ECMO was not used in our patients and no significant association with corticosteroids was found. [1, 5] Managing significant numbers of complex patients while wearing extensive personal protective equipment may have influenced infection prevention and control practice. However, while fungaemia rates were significantly lower prior to COVID-19 (Difference: 5.3%, 95% CI: 1.0-9.9; P: Candida albicans was the predominant (79.4%) species isolated irrespective of COVID-19 status, so the report by Rodriguez and colleagues confirming significant IC in COVID-19 patients caused by predominantly non-albicans species, including Candida auris highlights geographical variability. [4] Over the past five years only a single patient in Wales had C. auris isolated, so its absence from our cohorts is not unexpected and opposite to Colombia, where C. auris is endemic in certain regions, leading to healthcare transmission and outbreaks. [7, 8] As Candida auris has been predominately identified as a healthcare associated infection this potentially suggests that the increase is related to a change in practice associated with the pandemic and the impact of potentially unnecessary use of azoles in driving the emergence of resistant species. While the mortality rate in the Colombian study A c c e p t e d M a n u s c r i p t 4 was higher than that documented in Wales, it is unclear if this is associated with a delay in appropriate antifungal therapy, particularly in cases of non-albicans candidaemia It appears that IC is a significant complication of severe COVID-19 infection, but not necessarily directly associated with the disease itself, and it is essential that further research improves our understanding of risk. Active surveillance for IC and knowledge of local epidemiology is critical to minimizing the deleterious effects of this secondary infection.

PLW reports personal fees from Gilead, Pfizer, F2G, and MSD, and meeting sponsorship from Dynamiker, Bruker, and Launch, outside the submitted work. RD reports expert opinion fees from MSD and an educational grant from Gilead Sciences, outside the submitted work. MB reports personal fees from Gilead and meeting sponsorship from Abbvie, outside the submitted work. All other authors have no potential conflicts. M a n u s c r i p t 

A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU

COVID-19 and fungal superinfection

Candidemia in COVID-19 patients: incidence and characteristics in a prospective cohort compared to historical non-COVID-19 controls

Candida auris: a latent threat to critically ill patients with COVID-19

COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study

Case Series Study of Melioidosis, Colombia. Emerg Infect Dis

Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance

Six candidaemia, one Candida ascites and one Rhodotorula fungaemia, one patient had candidaemia with C. albicans and C. parapsilopsis

A c c e p t e d M a n u s c r i p t