Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies

Abstract

Background.: The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied.

Methods.: We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis.

Results.: We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66-2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use).

Conclusions.: HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV.

Keywords: bronchoalveolar lavage; hematologic malignancy.; hematopoietic cell transplant; human coronavirus; lower respiratory tract disease.

Figure 1.

A, Human coronavirus strain. Seasonal distribution of human coronavirus lower respiratory tract disease (LRTD). B, Respiratory copathogens in human coronavirus LRTD. Each color indicates category of copathogen as follows: white (viruses), gray (fungi), and dark gray (bacteria). Respiratory viral copathogens were detected in 12 patients, fungal copathogens were detected in 10 patients, and bacterial copathogens were detected in 8 patients. The number of patients (n = 30) with other respiratory copathogens does not equal the sum of detections for each respiratory copathogen (n = 36) owing to codetections of multiple copathogens in some subjects.Abbreviations: ADV, adenovirus; A. fumigutus, Aspergillus fumigatus; B. cepacia, Burkholderia cepacia; CMV, cytomegalovirus; C. neoformans, Cryptococcus neoformans; E. faecium, Enterococcus faecium; H. influenzae, Haemophilus influenzae; HMPV, human metapnuemovirus; NT, nontypeable strain due to unavailable sample; P. aeruginosa, Pseudomonas aeruginosa; PIV, parainfluenza virus; PJP, Pneumocystis jirovecii; RSV, respiratory syncytial virus; RV, rhinovirus; S. aureus, Staphylococcus aureus; VGS, Viridans group streptococci.

Figure 2.

Viral load of human coronavirus in bronchoalveolar lavage samples. The bars indicate median values and first and third quartiles.

Figure 3.

Kaplan-Meier overall survival curve by day 90 after diagnosis of lower respiratory tract disease without respiratory viral copathogens according to respiratory virus classification in hematopoietic cell transplant recipients. A, Kaplan-Meier overall survival curve in overall cohort (n = 286) (log-rank test, P = .78). B, Kaplan-Meier overall survival curve in patients without other copathogens (n = 173) (log-rank test, P = .47). C, Kaplan-Meier overall survival curve in patients with oxygen requirement at diagnosis (n = 178) (log-rank test, P = .78). D, Kaplan-Meier overall survival curve in patients without oxygen requirement at diagnosis (n = 108) (log-rank test, P = .78).