A National Strategy to Diagnose Coronavirus Disease 2019–Associated Invasive Fungal Disease in the Intensive Care Unit

Abstract

Background Fungal co-infection is a recognised complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in COVID-19 patients with severe respiratory distress are being reported, but comprehensive data is lacking. The aim of this study was to determine the incidence, risk factors and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress. Methods An evaluation of a national, multi-centre, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients. Results One-hundred and thirty-five adults (median age: 57, M/F: 2·2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12·6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P: 0.0387). The mortality rate was reduced by the use of antifungal therapy (Mortality: 38·5% in patients receiving therapy versus 90% in patients not receiving therapy (P: 0.008). The use of corticosteroids (P: 0.007) and history of chronic respiratory disease (P: 0.05) increased the likelihood of aspergillosis. Conclusions Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.

Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance

“…Unfortunately, the diagnostic yield of serum galactomannan is low in CAPA as, at best, 20% of patients showed positive results, and proven CAPA cases have been reported with negative serum galacto mannan. 9,12 This low sensitivity is in line with published performance of serum galactomannan detection in non-neutropenic patients in ICUs but lower than the 65% sensitivity of serum galactomannan in patients with IAPA. Overall, serum galactomannan has decreased value for excluding CAPA.…”

“…IPA is emerging as a serious secondary infection in patients with COVID-19 and ARDS, and two studies have indicated excess mortality rates of 16% and 25% compared with patients without evidence for aspergillosis. 11,12 These excess mortality rates are similar to that found for patients with IAPA, in whom the survival rate in intensive care units (ICUs) was 24% lower than in patients without this secondary infection. 1 CAPA diagnosis was associated with ICU mortality in a logistic regression model, even after adjustment for age, need for renal replacement therapy, and sequential organ failure assessment score at ICU admission.…”

“…Despite all of the limitations previously given, the following statement can be made for critically ill patients with COVID-19: multiple pulmonary nodules or lung cavitation should prompt thorough investigation for IPA, as they are rarely seen with COVID-19 alone and have been described in a small proportion of patients with CAPA to date. 12 Frequently observed radiological features of IPA, such as the halo sign, are not sufficient to define CAPA without mycological evidence. This feature is insufficient because the halo sign suggests local infarction, and an intrinsic part of severe COVID-19 is in-situ thrombosis due to endotheliopathy.…”

“…11 Indeed, chronic corticosteroid treatment was substantially more frequent in patients with CAPA, and corticosteroid use was more frequent in patients who did not survive. 11,12 Furthermore, dexamethasone treatment of patients with severe COVID-19 is likely to increase in the near future, saving many lives, as shown in the RECOVERY trial. 23 Dexamethasone treatment and anti-IL-6-directed strategies might, however, also result in an increased susceptibility to superinfections, 23,24 including IPA in patients with severe COVID-19, 25 and could lead to increases in CAPA incidence, emphasising the need for guidance.…”

“…[5][6][7][8][9][10] Indeed, in a prospective cohort of 108 criti cally ill patients with ARDS, a higher 30-day mortality was observed in patients with CAPA than in patients without aspergillosis (44% vs 19%), and the association of COVID-19-associated fungal disease with mortality was also supported by another study. 11,12 The population of patients with CAPA harbours many baseline prognostic factors with negative effects on survival, 13 which might be further compromised by azole-resistant CAPA, with an increasing number of patients reported in the literature. [14][15][16] Respiratory viruses cause direct damage to the air way epithelium, enabling aspergillus to invade tissue.…”