Rhinovirus Infections among Hematopoietic Stem Cell Transplant Recipients: A Pre-Transplant Dilemma?

Abstract

Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients’ depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were transplanted between 1 January 2010 and 31 October 2019 in the Geneva University Hospitals with at least one RVI before or after transplantation. At least one RVI was detected in 319/533 (63.5%) transplanted patients. Rhinoviruses were most frequently identified (37%), followed by human coronaviruses (17.1%), parainfluenza viruses (13.9%), and influenza viruses (9.9%). First infection in the post-transplant period occurred at a mean time of 334 days (SD 338). Specific analysis of a subgroup of 65 patients with pre-transplant RVIs was performed. Among them, 39 (59%) patients had symptoms and 14 (21.2%) had a lower respiratory tract infection. Four patients (6.1%) (three rhinovirus and one influenza) needed an intensive care unit admission, of which, three (4.5%) (two rhinovirus and one influenza) were intubated. The patient with influenza infection diagnosed the day of the transplantation died within the first 30 days of the infection. Two patients with rhinovirus infection died within 3 months of unrelated causes. Our data show that rhinovirus infections are predominant in allo-HSCT patients, including among pre-transplant infections; however, mortality due to pre-transplant RVI is low and was only clearly identified in one patient with influenza infection. RVI within the month preceding allo-HSCT is not associated with direct morbidity or mortality in this cohort.

The present and future of blood virome in allogeneic hematopoietic cell transplant recipients

“…The prevalence of human polyomavirus infection is very high in the adult populations [5,17 ▪ ]. Apart from the well known pathogenic BK polyomavirus regularly screened for in allogeneic HCT recipients, recent studies identified the frequent presence of JC polyomavirus (JCPyV) as well as several novel polyomaviruses in plasma, such as Merkel cell polyomavirus (MCPyV), HPyV6 and HPyV7, albeit of unclear clinical significance for the time being [5,17 ▪ ]. In rare cases, JCPyV reactivation causes progressive multifocal leukoencephalopathy in the immunocompromised host; however, in the vast majority of allogeneic HCT patients, JCPyV reactivation has not yet been linked to any clinical manifestation or impact on HCT outcome [31].…”

“…With the emergence of the virome concept, several studies have been performed by the Geneva group in the last years to better describe the blood virome among allogeneic HCT patients [15,16 ▪ ,17 ▪ ,18 ▪▪ ,19 ▪ ] (Table 1). In a study by Vu et al [15], mNGS was used on plasma samples of 40 patients to provide a description of the blood virome at 1-month post-HCT.…”

“…HPgV-1 infection was shown to be highly prevalent with 42% of patients testing positive at least once up to 1-year post-HCT as well as to be persistent with HPgV-1 RNA plasma detection up to 6–12 months in 20% of patients. More recently, Zanella et al [17 ▪ ] described the prevalence of 17 DNA and 3 RNA viruses detected in plasma samples by using specific r(RT-)PCR screening up to 1-year posttransplantation in 109 patients receiving allogeneic HCT between 2017 and 2019 at Geneva University Hospitals. Torque teno virus (TTV, an Anelloviridae ) infection was almost universal, followed by HPgV-1, both showing a peak prevalence at 6 months post-HCT (TTV 96%, HPgV-1 36%).…”

Respiratory viruses in hematopoietic cell transplant candidates: impact of preexisting lower tract disease on outcomes

“…15 A recent study found no direct association between pretransplant RVI and mortality in adult HCT patients. 16 Using meta-transcriptomic sequencing of pre-HCT bronchoalveolar lavage (BAL) samples, a third study identified distinct signatures of viral infection and commensal bacterial depletion that were associated with significantly increased post-HCT lung injury and fatal lung injury. 17 To date, studies have been limited by small size, precluding multivariable statistical analysis of factors associated with outcome such as location of infection or conditioning regimen.…”

Nosocomial human parainfluenza virus type 3 outbreak in immunocompromised patients, and possible lessons from the SARS-CoV-2 pandemic

“…In order to better understand the dynamics of nosocomial spread and clinical manifestations of HPIV-3 infections we retrospectively reviewed the results of all respiratory panel PCR tests from nasopharyngeal swabs performed on 883 patients at our hospital in an 8-month period (November 2016 to June 2017) surrounding the outbreak. We compared clinical manifestations and outcomes of patients infected with HPIV-3 (cases) and patients (controls) infected with rhino-/enteroviruses, which are the most frequent cause of respiratory virus infections in both immunocompetent and immunocompromised individuals [ 4 ]. Cases and controls were matched for age, gender, immunosuppressive treatment and HCT.…”