Incidence, risk factors, and outcome of pulmonary invasive fungal disease after respiratory virus infection in allogeneic hematopoietic stem cell transplantation recipients

Abstract

Background: There is growing evidence that community-acquired respiratory virus (CARV) increases the risk of pulmonary invasive fungal disease (IFD) in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting. To date, there is a lack of knowledge regarding the risk factors (RFs), as well as the most critical period for subsequent onset of IFD after CARV infections in allo-HSCT recipients.

Methods: In this prospective longitudinal observational CARV survey, we analyzed the effect of CARV on subsequent IFD development in 287 adult allo-HSCT recipients diagnosed with 597 CARV episodes from December 2013 to December 2018. Multiplex PCR panel assays were used to test CARVs in respiratory specimens.

Findings: Twenty-nine out of 287 allo-HSCT recipients (10%) developed IFD after a CARV episode. The median time of IFD onset was 21 days (range, 0-158 days) from day of the first CARV detection. Generalized estimating equation model identified 4 risk factors for IFD: ATG-based conditioning regimen [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.05-5.2, P = .038], CARV lower respiratory tract disease (OR 10.6, 95% CI 3.7-30.8, P < .0001), CARV infection during the first year after transplant (OR 5.34, 95% CI 1.3-21.8, P = .014), and corticosteroids during CARV (OR 2.6, 95% CI 1.1-6.3, P = .03).

Conclusion: Allo-HSCT recipients conditioned with ATG and under corticosteroid therapy at the time of CARV LRTD during the first year after transplant may require close monitoring for subsequent IFD.

Keywords: allogeneic hematopoietic stem cell transplantation; community-acquired respiratory virus; immunodeficiency score index; invasive Aspergillosis; invasive pulmonary fungal disease.