Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms

Wei Ju Chen, Jyh Yuan Yang, Jih Hui Lin, Cathy S.J. Fann, Valeriy Osyetrov, Chwan Chuen King, Yi Ming Arthur Chen, Hsiao Liang Chang, Hung Wei Kuo, Fong Liao, Mei Shang Ho

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21 Citations (Scopus)

Abstract

Background. A high initial or peak severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 108 SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P < .0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P = .0015, by trend test). Virus shedding was found to be higher among male patients (P = .0014, by multivariate logistic regression) and among older patients (P = .015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P = .014) and 1A (P = .031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P = .034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P = .008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).

Original languageEnglish
Pages (from-to)1561-1569
Number of pages9
JournalClinical Infectious Diseases
Volume42
Issue number11
DOIs
Publication statusPublished - Jun 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Chen, W. J., Yang, J. Y., Lin, J. H., Fann, C. S. J., Osyetrov, V., King, C. C., Chen, Y. M. A., Chang, H. L., Kuo, H. W., Liao, F., & Ho, M. S. (2006). Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms. Clinical Infectious Diseases, 42(11), 1561-1569. https://doi.org/10.1086/503843