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