title: Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms.
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).
  
  
  CONCLUSIONS
  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).
authors.affiliation: Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Chen
authors.forename: Jyh-Yuan
authors.initials: JY
authors.lastname: Yang
authors.forename: Jih-Hui
authors.initials: JH
authors.lastname: Lin
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Valeriy
authors.initials: V
authors.lastname: Osyetrov
authors.forename: Chwan-Chuen
authors.initials: CC
authors.lastname: King
authors.forename: Yi-Ming Arthur
authors.initials: YM
authors.lastname: Chen
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chang
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Kuo
authors.forename: Fong
authors.initials: F
authors.lastname: Liao
authors.forename: Mei-Shang
authors.initials: MS
authors.lastname: Ho
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009305:Nasopharynx / Q000821:virology*; D011110:Polymorphism, Genetic; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D051841:Transcription Factor RelB / Q000235:genetics; D019562:Viral Load; D017201:Virus Shedding / Q000235:genetics*
chemical_list: C095202:FGL2 protein, human; D007375:Interleukin-1; D020382:Interleukin-18; C497593:RELB protein, human; D051841:Transcription Factor RelB; D005340:Fibrinogen