Risk factors for seasonal human coronavirus lower respiratory tract infection after hematopoietic cell transplantation

Abstract

Data are limited regarding risk factors for lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) and the significance of virologic documentation by bronchoalveolar lavage (BAL) on outcomes in hematopoietic cell transplant (HCT) recipients. We retrospectively analyzed patients undergoing allogeneic HCT (4/2008-9/2018) with HCoV (OC43/NL63/HKU1/229E) detected by polymerase chain reaction during conditioning or post-HCT. Risk factors for all manifestations of LRTI and progression to LRTI among those presenting with HCoV upper respiratory tract infection (URTI) were analyzed by logistic regression and Cox proportional hazard models, respectively. Mortality rates following HCoV LRTI were compared according to virologic documentation by BAL. A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had URTI alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI (median, 16 days; range, 2-62 days). Multivariable logistic regression analyses showed that male sex, higher immunodeficiency scoring index, albumin <3 g/dL, glucose >150 mg/dL, and presence of respiratory copathogens were associated with occurrence of LRTI. Hyperglycemia with steroid use was associated with progression to LRTI (P < .01) in Cox models. LRTI with HCoV detected in BAL was associated with higher mortality than LRTI without documented detection in BAL (P < .01). In conclusion, we identified factors associated with HCoV LRTI, some of which are less commonly appreciated to be risk factors for LRTI with other respiratory viruses in HCT recipients. The association of hyperglycemia with LRTI might provide an intervention opportunity to reduce the risk of LRTI.

Predicting risk of progression to lower respiratory tract infection in allogeneic hematopoietic cell transplant recipients with respiratory viral infections: where are we now?

“…Influenza vaccines in allogeneic HCT recipients may also impact outcomes, but this remains to be determined in future studies [ 7 ]. The variable definitions in this study were consistent with those in prior studies by their group and others [ 6 , 8 , 9 ], including LRTI and lymphopenia. The Use of consistent variable definitions across studies increases the reliability of quantitative models like the ISI score in predicting outcomes from respiratory viral infections, which will lead to better design and planning of future clinical trials in this patient population.…”

“…These factors include neutropenia (absolute neutrophil count <500/μl), lymphocytopenia (absolute lymphocyte count <200/μl), patient age of at least 40 years, use of a myeloablative conditioning regimen, acute or chronic graft-versus-host disease, use of corticosteroids within 30 days of RSV infection, and transplantation within 30 days of or in the pre-engraftment period during RSV infection [ 1 ]. This quantifiable ISI stratifies patients into low-risk (0–2), moderate-risk [ 3 – 6 ], and high-risk (≥7) categories regarding progression or death. Studies have validated the ISI for different respiratory viral infections in allogeneic and autologous HCT recipients at multiple centers with varying success [ 2 – 6 ].…”

“…This quantifiable ISI stratifies patients into low-risk (0–2), moderate-risk [ 3 – 6 ], and high-risk (≥7) categories regarding progression or death. Studies have validated the ISI for different respiratory viral infections in allogeneic and autologous HCT recipients at multiple centers with varying success [ 2 – 6 ].…”

Albumin and infection following a procedure: a Mendelian Randomization study

“…IFP infection following a procedure, MR Mendelian randomization, DM/SIFP Diagnosesmain/secondary ICD10: T81.4 infection following a procedure, r2 the proportion of phenotypic variation explained by genetic variants, SD standard deviation Discussion Some retrospective cohort studies reported albumin as an independent risk factor for infections. Ogimi et al suggested that albumin < 3g/dL was associated with occurrence of seasonal human coronavirus lower respiratory tract infection [37]. Zhongyuan et al suggested that preoperative serum albumin < 3.5g/dL was signi cantly correlated with surgical site infection (SSI) and postoperative serum albumin < 3.0 g/dL was signi cantly correlated with surgical wound dehiscence in lumbar spine surgeries [12].…”

Respiratory virus infections after allogeneic stem cell transplantation: Current understanding, knowledge gaps, and recent advances

“…Initial thoughts suggested that hCoV infections were relevant only in the context of co‐infections 16,186 . In contrast, recent studies 11,98 have shown that around 9% to 33% of hCoV infections progress to LRTD and lead to hospitalization in 19% of cases. In this line, the presence of hCoV in BAL samples was significantly associated with high rates of respiratory support and mortality, 187 similar to other CARVs including RSV, influenza virus and hPiV 187 .…”