Fungal infections common in COVID-19 patients who require mechanical ventilation

Patients with COVID-19 who received mechanical ventilation while admitted to the intensive care unit (ICU) have an elevated risk of invasive fungal infections (IFIs), according to results of the MYCOVID study from France. Furthermore, patients with COVID-19–associated pulmonary aspergillosis (CAPA) may be at an increased risk for death.

“The high prevalence and mortality associated with IFIs, particularly invasive aspergillosis and candidaemia, highlight the need for a high index of suspicion for patients with severe COVID-19 in the ICU, and an urgent necessity of implementing active surveillance,” the authors stressed.

This multicentre, observational study involved 509 adults* (mean age 59.4 years, 79 percent male, mean BMI 29.3 kg/m²) with RT-PCR–confirmed SARS-CoV-2 who required mechanical ventilation for acute respiratory distress syndrome (ARDS) while admitted to the ICU. All participants underwent once- or twice-weekly screening for the presence of respiratory fungal microorganisms throughout the period of mechanical ventilation until ICU discharge.

Patients were in the ICU for a mean 32.7 days and mean duration of mechanical ventilation was 27.1 days. A total of 186 deaths occurred in the ICU (37 percent). The most common comorbidities at baseline were lymphopenia, hypertension, and diabetes which were documented in 64, 50, and 33 percent of patients, respectively.

Twenty-five percent of patients (n=128) had 138 episodes of proven or probable (pr/pb) or possible IFIs, with 76 patients (15 percent) fulfilling criteria for pr/pb CAPA. [Lancet Respir Med 2021;doi:10.1016/S2213-2600(21)00442-2]

Seventy-six percent of patients with pr/pb CAPA received antifungal treatment, with 29 patients receiving more than one drug. The most common treatments were voriconazole and fluconazole (76 and 52 percent, respectively).

Seventy-three, 15, and 10 percent of patients were also diagnosed with bacterial ventilator-associated pneumonia (VAP), herpes simplex virus type 1, and cytomegalovirus infection, respectively.

Patients who were older than 62 years had an elevated risk of pr/pb CAPA (odds ratio [OR], 2.34, 95 percent confidence interval [CI], 1.39–3.92; p=0.0013). Other factors that were associated with an increased risk of pr/pb CAPA were mechanical ventilation for >14 days (OR, 2.16, 95 percent CI, 1.14–4.09; p=0.019) and dexamethasone and anti-IL-6 combination therapy (OR, 2.71, 95 percent CI, 1.12–6.56; p=0.027).

This latter finding requires further study due to the small number of patients on this combination therapy, said the authors, who highlighted the lack of association with either drug alone with pr/pb CAPA.

Seven percent of patients (n=38) had ≥1 other pr/pb IFIs, with 32 having candidaemia, six having invasive mucormycosis, and one having invasive fusariosis.

“The high prevalence observed in this study might be related to several factors, such as the homogeneous population of patients with severe COVID-19 and ARDS, the rigorous monitoring dedicated to fungal diagnosis, the role of previous comorbidities, and the role of the treatment received,” the authors said.

Elevated mortality risk

There was a significantly higher risk of death in the ICU among patients with vs without pr/pb CAPA (61.8 percent vs 32.1 percent; p<0.0001).

Univariate analysis showed certain factors were associated with an increased risk of in-ICU mortality including older age, immunosuppression, solid organ transplantation, and SAPS II and SOFA** scores. Certain treatments were also tied to mortality risk (eg, lopinavir-ritonavir and anti-IL-1), as was the presence of Aspergillus spp in respiratory samples.

While aspergillosis and candidaemia were associated with increased mortality, VAP and viral infections were not. 

After adjusting for candidaemia, patients with pr/pb CAPA were at a higher risk of death (hazard ratio [HR], 1.45, 95 percent CI, 1.03–2.03; p=0.033) compared with those without pr/pb CAPA. Patients aged >62 years (HR, 1.71, 95 percent CI, 1.26–2.32; p=0.0005) and those who had undergone solid organ transplantation (HR, 2.46, 95 percent CI, 1.53–3.95; p=0.0002) were also at a greater mortality risk.

Additionally, treatment with voriconazole or isavuconazole did not affect mortality risk among patients with pr/pb CAPA, though the study was not designed to assess the effect of antifungal treatment.

“[T]he increased mortality in patients with pr/pb CAPA warrants consideration of early antifungal strategies, such as antifungal prophylaxis or pre-emptive strategies for high-risk patients, including those receiving dexamethasone combined with anti-IL-6, as well as the implementation of air treatment measures,” the authors said.