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

Abstract

Pretransplant respiratory virus infections (RVIs) have been shown to negatively impact hematopoietic cell transplantation (HCT) outcomes. The impact of and need for delay of HCT for pretransplant infection with human rhinovirus (HRV) or endemic human coronavirus (HCoV) (229E, OC43, NL63, and HKU1) remains controversial. We analyzed the impact of symptomatic RVI within <90 days prior to HCT on overall mortality, posttransplant lower respiratory tract disease (LRD), and days alive and out of hospital (DAOH) by day 100 post HCT in multivariable models. Among 1,643 adult HCT recipients (58% allogeneic recipients), 704 (43%) were tested for RVI before HCT and 307 (44%) tested positive. HRV was most commonly detected (56%). Forty-five (15%) of 307 HCT recipients had LRD with the same virus early after HCT. Pretransplant upper respiratory infection (URI) with influenza, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza virus, HRV or endemic HCoV was not associated with increased overall mortality or fewer DAOH. However, in allogeneic recipients who received myeloablative conditioning, LRD due to any respiratory virus, including HRV alone, was associated with increased overall mortality (adjusted hazard ratio 10.8 [95% CI 3.29, 35.1] for HRV and 3.21 [95% CI 1.15, 9.01] for all other viruses). HRV LRD was also associated with fewer DAOH. Thus, the presence of LRD due to common respiratory viruses, including HRV, before myeloablative allogeneic HCT was associated with increased mortality and hospitalization. Pretransplant URI due to HRV and endemic HCoV was not associated with these outcomes. Improved management strategies for pretransplant LRD are warranted.

Monoclonal antibodies for prophylaxis and treatment of respiratory viral infections

“…Finally, it is important to note that mAbs are currently available for only two viruses, RSV and SARS-CoV-2. There is a significant unmet need for mAbs against other respiratory viruses like influenza, human metapneumovirus, and the parainfluenza viruses that afflict immunocompromised patients and cause significant morbidity and mortality [4 ▪ ,44 ▪ ].…”

“…Immunocompromised patients have increased susceptibility to severe complications due to respiratory viral infections, including death. For example, hematopoietic stem cell transplant (HCT) recipients represent a subgroup of immunocompromised patients that are extremely vulnerable to respiratory viruses due to loss of immunity after conditioning chemotherapy [1 ▪ –4 ▪ ]. This is modeled in Fig.…”

Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022)

“…Multiple studies have shown that age and a shorter time from transplantation to COVID-19 are associated with poor outcomes 1 , 4 , 27 . For other respiratory viruses, the presence of LRTI and myeloablative conditioning are associated with increased risk of post-HCT complications 28 . In a recent systematic review, a higher performance status was associated with decreased mortality in HCT recipients acquiring COVID-19 at all stages following transplant (HR=0.83, 95%CI 0.74-0.93, p=0.001) 29 .Based on our expert opinion and clinical experience in management of COVID-19 among this population, we provide a summary of recommendations on evaluation of HCT and cellular therapy candidates in table 1 .…”

Coronavirus Disease-2019 in the Immunocompromised Host

“…Since that time, SARS-CoV-2 has been responsible for over 6 million deaths from Coronavirus Disease 2019 (COVID-19) 1 . Respiratory viral infections, in general, place an outsized burden on immunocompromised hosts, and increase the mortality 2 . Therefore, there was significant concern from the outset of the pandemic that SARS-CoV-2 infection would similarly impact immunocompromised patients disproportionately.…”

“…Indeed, mortality was over twofold higher among immunocompromised patients with influenza pneumonia. Other respiratory viruses also affect the immunocompromised; a recent retrospective cohort study of 1643 hematopoietic cell transplant patients found increased mortality in allogeneic recipients infected with human rhinovirus (HRV) and adenovirus lower respiratory infections 2 . Finally, human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) have long been associated with increased mortality amongst hematopoietic cell transplant recipients 8 .…”