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

Clin Infect Dis. 2006 Jun 1;42(11):1561-9. doi: 10.1086/503843. Epub 2006 Apr 25.

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 10(8) 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 NF kappa B 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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Fibrinogen / genetics
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-18 / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nasopharynx / virology*
  • Polymorphism, Genetic*
  • SARS Virus / physiology*
  • Transcription Factor RelB / genetics
  • Viral Load
  • Virus Shedding / genetics*

Substances

  • FGL2 protein, human
  • Interleukin-1
  • Interleukin-18
  • RELB protein, human
  • Transcription Factor RelB
  • Fibrinogen