Invasive Fungal Infections Associated with COVID-19 Infections in Solid Organ Transplant Recipients

ABSTRACT

Purpose: Invasive fungal infection (IFI) complicating Coronavirus disease of 2019 (COVID-19) has been increasingly recognized. IFI is a common opportunistic infection in solid organ transplant (SOT), but association with COVID-19 is unknown. Method(s) This was a retrospective study of all SOT recipients hospitalized with COVID-19 between March 2020 and Oct 2021. IFI was defined based on EORTC/ MSG criteria. Result(s) 107 SOT recipients were hospitalized due to COVID-19. 17 patients were excluded because they were on a systemic antifungal agent on admission. Median age was 62 yrs. 46% were female. 59% (53) were recipients of kidney, 17% (15) of lung, 11% (10) each of heart and liver, and 2% (10) of small bowel. 8% (7) of patients developed IFI within 90 days of COVID-19 (2 proven and 5 probable) (Table) 3 due to yeasts (2 bloodstream and 1 lung), and 4 pulmonary aspergillosis. Median time from COVID-19 diagnosis to IFI was 22 days (1d to 78d). Mechanical ventilation (P = 0.01) and augmented immunosuppression (p = 0.04) were risk factors for IFI;receipt of dexamethasone or IL-6 inhibitor were not risk factors. IFI associated with more prolonged hospital stay (median of 23 days (7-120d) vs 10d (1-80d), respectively). The 90-day mortality after COVID-19 diagnosis was 23% (21), higher for patients with IFI (57% vs 20%;p=0.04). By univariate analysis, the risk factors for death were use of dexamethasone (p=0.011), IL-6 inhibitor (p=0.001), and IFI (p=0.049);SARS-CoV-2 monoclonal antibody (Mab) was protective (p=0.06). By multivariate analysis, receipt of IL-6 inhibitor (p=0.001) and IFI (p=0.009) were independent risk factors for death;Mab was protective (p=0.02). Overall, 18% (16) patients received systemic antifungals (AF);11% (9) received AFs without any IFI diagnosis and they all received anti-mold agents. Conclusion(s) The incidence of IFI complicating COVID-19 was 8%, and IFI was associated with a higher mortality. The association between receipt of IL-6 inhibitor and death among SOT patients is of concern. Risk and benefit of this agent along with it's side effect should be carefully evaluated in larger trials of SOT and other immunosuppressed COVID-19 patients. (Table Presented).