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Clinical significance of seasonal human coronaviruses in immunocompromised host

大宜見 力 富山大学

2022.01.26

概要

〔目的〕
Respiratory viruses can frequently cause lower respiratory tract disease (LRTD) in immunocompromised hosts, which is associated with significant morbidity and mortality. The development and widespread use of sensitive molecular diagnostic techniques have contributed to better understanding of epidemiology and clinical manifestation of four seasonal human coronavirus (HCoV) species (OC43, NL63, HKU1, and 229E) in general population. However, the data are limited regarding whether clinical features differ among four species and how immunocompromised state plays in a role on the disease severity. I investigated the significance of HCoV detected in bronchoalveolar lavage (BAL) in immunocompromised hosts as well as risk factors for LRTD in immunocompromised and non-immunocompromised children.

〔方法並びに成績〕
First study
All hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancy with HCoV detected in clinical BAL samples from patients at the Fred Hutchinson Cancer Research Center, University of Washington or Seattle Children’s Hospital from May 2006 through February 2016 were enrolled. Three additional HCT recipients with HCoV detected in BAL samples from a previously reported cohort were also enrolled. Only patients with first episodes of HCoV LRTD defined as detection of HCoV in BAL were used for outcome analysis. Clinical outcomes following HCoV LRTD were compared. Furthermore, mortality rate within 90 days following HCoV LRTD were also compared with that following LRTD due to respiratory syncytial virus, parainfluenza virus or influenza among HCT recipients in multivariable models.
There were 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis of LRTD and 19 (54%) died within 90 days following the diagnosis. Respiratory copathogens were detected in more than half of cases (57%, 21/37); however, mortality rates were not different between patients with and without copathogens (P = .65). Mortality rate associated with HCoV LRTD in HCT recipients was not significantly different from that seen with RSV, influenza, and PIV LRTD.

［Summary］
HCoV LRTD in patients with HCT or hematologic malignancy is associated with high rates of oxygen use and mortality regardless of presence of respiratory copathogens. Mortality associated with HCoV LRTD in HCT recipients is comparable to that seen with established respiratory pathogen.

Second study
All pediatric patients who presented to Seattle Children’s Hospital for acute care and in whom HCoV was detected in clinical nasal samples using a multiplex respiratory PCR assay between October 2012 and March 2016 were enrolled. LRTD was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. Severe LRTD was defined as necessitated oxygen use. Risk factors for LRTD and severe LRTD in children were examined in logistic regression models with focus on immunocompromised state, type of species and presence of respiratory copathogen.
Eighty-five immunocompromised and 1152 non-immunocompromised children with HCoV infection were included. In multivariable models, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2–4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models; however, HCoV species were associated with risks of neither LRTD nor severe LRTD.

［Summary］
In children, LRTD was associated with the presence of a non-HCoV respiratory copathogen, especially RSV, but not with a particular HCoV species. I also found an association between an immunocompromised state and an increased risk of serious HCoV-related LRTD.

〔総括〕
HCoV LRTD could contribute to significant morbidity and mortality in immunocompromised host. HCoV species were not associated with LRTD in children; however, an immunocompromised state was associated with a higher risk of severe LRTD. Given the universal distribution of HCoVs, the appreciation of HCoV as an important lower respiratory tract pathogen and recognition of risk factors for severe respiratory illness could impact clinical management including risk stratification in future studies and provide a rationale to develop novel antiviral therapies.

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参考文献

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Chapter 2

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