Candidemia in Coronavirus Disease 2019 (COVID-19) Patients: Incidence and Characteristics in a Prospective Cohort Compared With Historical Non–COVID-19 Controls

To the Editor—We read with interest the article by White and colleagues, who provide insights on invasive fungal infections in coronavirus disease 2019 (COVID-19) patients [1]. The authors describe a significant proportion of invasive yeast infections, especially candidemia. To date, it is not clear if the incidence of candidemia in COVID-19 patients is higher than expected. Moreover, no comparison of clinical presentation and outcomes between patients with and without COVID-19 is available. To investigate these points, we compared the incidence and characteristics of candidemia in a prospective cohort of patients with severe acute respiratory syndrome coronavirus 2 infection to those of a historical cohort of non–COVID-19 controls. We included patients with candidemia (defined as 1 or more positive blood cultures for Candida spp.) hospitalized at the San Raffaele Hospital (Milan, Italy) with COVID-19 from 15 February 2020 to 30 June 2020 and patients hospitalized for any reason from 1 January 2017 to 31 December 2017 (historical non–COVID-19 cohort). An ethical committee approved data collection for both cohort studies. The Pearson χ 2 test and Mann-Whitney U test were applied, as appropriate. The incidence rate was calculated as events per 10.000 person-days of follow-up (PDFU) and compared using Poisson regression. Statistical analysis was performed with SPSS-v.20 (IBM, Chicago, IL). We identified 21 and 51 patients in the COVID-19 and historical cohorts, respectively (Table 1). The incidence rate of candidemia was significantly higher in patients with COVID-19 (10.97 [6.79–16.76] vs 1.48 [1.10–1.95] cases per 10.000 PDFU; P < .001). Characteristics of the 2 Cohorts of Patients With Candidemia Values are reported as median, interquartile range, or frequency (%). P-values <0.05 are presented in bold. Abbreviation: COVID-19, coronavirus disease 2019. aLess than 5 years of negative follow-up since the last potentially curative intervention. bAdministration of chemotherapies during the 90 days before candidemia. cAdministration of antimicrobials during the 14 days before candidemia. dAdministration of immunomodulating drugs (anakinra, tocilizumab, reparixin, mavrilimumab, sarilumab) and/or immunosuppressive drugs (cyclophosphamide, tacrolimus, mycophenolate) in the last 30 days before candidemia. eAdministration of 0.5–1 mg/kg of prednisone equivalent in the last 30 days before candidemia. fPositive Candida spp. culture from nonsterile site and/or clinical signs and symptoms compatible with skin or mucous membrane fungal infection. gAny major surgical procedure in the last 30 days. hTwo negative sets of blood cultures collected after at least 48 hours from initiation of an appropriate therapy. Characteristics of the 2 Cohorts of Patients With Candidemia Values are reported as median, interquartile range, or frequency (%). P-values <0.05 are presented in bold. Abbreviation: COVID-19, coronavirus disease 2019. aLess than 5 years of negative follow-up since the last potentially curative intervention. bAdministration of chemotherapies during the 90 days before candidemia. cAdministration of antimicrobials during the 14 days before candidemia. dAdministration of immunomodulating drugs (anakinra, tocilizumab, reparixin, mavrilimumab, sarilumab) and/or immunosuppressive drugs (cyclophosphamide, tacrolimus, mycophenolate) in the last 30 days before candidemia. eAdministration of 0.5–1 mg/kg of prednisone equivalent in the last 30 days before candidemia. fPositive Candida spp. culture from nonsterile site and/or clinical signs and symptoms compatible with skin or mucous membrane fungal infection. gAny major surgical procedure in the last 30 days. hTwo negative sets of blood cultures collected after at least 48 hours from initiation of an appropriate therapy. Candida albicans was the most frequently involved pathogen, even though non-albicans Candida spp. were detected in a considerable proportion of patients (33.3% vs 47.1%; P = .285). Infective endocarditis and endophthalmitis were rarely encountered. Candidemia clearance was obtained in most patients (71.4% vs 72.5%; P = .923), but overall mortality was high (57.1% vs 58.8%; P = .895). COVID-19 patients had a lower median Charlson comorbidity index, and no differences were detected in prior use of antibiotics, antifungal agents, parenteral nutrition, or other conditions potentially predisposing to candidemia, except for a higher proportion of patients with solid malignancies and recent chemotherapies in the historical cohort. COVID-19 patients were more likely to be in the intensive care unit (ICU; 66.7% vs 29.4%; P = .003) and to be treated with immunosuppressive agents (61.1% vs 32.7%; P = .035); the proportion of patients on glucocorticoids was not different (44.4% vs 30.6%; P = .291). When calculated for ICU patients only, the incidence rate of candidemia was still markedly higher in COVID-19 patients (81.68 [44.46–137.10] vs 14.46 [8.09–23.84] cases per 10.000 PDFU; P = < .001). Limitations of this work include the monocentric retrospective design and limited sample size. In conclusion, we observed an increased incidence of candidemia in hospitalized patients with COVID-19 compared with a historical non–COVID-19 cohort. We found no imbalance in several predisposing risk factors for candidemia, with the notable exception of a higher proportion of patients in the ICU and on immunosuppressive agents in the COVID-19 cohort. A COVID-19–induced predisposition to candidemia, possibly linked to previously reported alterations such as immune paralysis, enhanced intestinal translocation [2], and switch of microbiota toward Candida spp. [3], should be explored in further studies. Members of COVID-BioB Study Group: Diana Canetti, Barbara Castiglioni, Chiara Oltolini, Chiara Tassan Din, Caterina Conte, Giacomo Monti, Lorenzo Dagna, Massimo Clementi, Patrizia Rovere Querini, Fabio Ciceri, Moreno Tresoldi, Paola Cinque, Adriano Lazzarin, Alberto Zangrillo, Antonio Secchi, Emanuele Bosi, Paolo Scarpellini, and Antonella Castagna. Acknowledgments. The authors thank all the physicians, nurses, and healthcare workers of San Raffaele Hospital whose efforts have contributed to mitigate the impact of the coronavirus disease 2019 pandemic. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.