title: Low serum levels of CCL5 are associated with longer duration of viral shedding in norovirus infection.
abstract: BACKGROUND
  The mechanisms that determine the duration of fecal shedding of norovirus in humans have not been described in detail.
  
  
  OBJECTIVE
  We investigated serum inflammatory mediator levels in relation to the duration of viral shedding in norovirus infection.
  
  
  METHODS
  A prospective cohort study of patients hospitalized with acute norovirus genogroup II infection. Rectal swab samples were obtained at inclusion and day 7, 14, 21 and 28. Serum levels of 42 inflammatory mediators were determined with a Luminex-based cytokine assay. Sera from 20 healthy blood donors served as controls.
  
  
  RESULTS
  Altogether, 28 patients (54% women, median age 83 years, median duration of symptoms 3 days) were included. Twelve subjects cleared the virus within 14 days and 16 were norovirus-RNA positive for >21 days, constituting the two study groups ("rapid" vs. "slow" clearance). Individuals with norovirus infection had higher levels of IL-18, CXCL9, CXCL10, soluble IL-2 receptor and macrophage migration inhibitory factor (MIF), compared to controls (p<0.05), with the highest median concentrations in the slow clearance group. In contrast, CCL5 levels were lower in the slow compared to the rapid clearance group (median 54 vs. 134 ng/mL, p<0.05), and lower in norovirus-infected patients than in controls.
  
  
  CONCLUSIONS
  Low levels of CCL5 were associated with longer duration of viral shedding, suggesting that CCL5 may influence the clearance of norovirus.
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Diagnosvägen 21, Gothenburg SE-416 50, Sweden. Electronic address: lars.gustavsson@microbio.gu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Gustavsson
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Diagnosvägen 21, Gothenburg SE-416 50, Sweden. Electronic address: susann.skovbjerg@vgregion.se.
authors.forename: Susann
authors.initials: S
authors.lastname: Skovbjerg
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Diagnosvägen 21, Gothenburg SE-416 50, Sweden. Electronic address: magnus.lindh@microbio.gu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Diagnosvägen 21, Gothenburg SE-416 50, Sweden. Electronic address: johan.westin@infect.gu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Diagnosvägen 21, Gothenburg SE-416 50, Sweden. Electronic address: lars-magnus.andersson@infect.gu.se.
authors.forename: Lars-Magnus
authors.initials: LM
authors.lastname: Andersson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017250:Caliciviridae Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D018946:Chemokine CCL5 / Q000097:blood*; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000097:blood / Q000276:immunology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000235:genetics*; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D017201:Virus Shedding
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D012367:RNA, Viral
keywords: CCL5; Cytokines; Norovirus; Viral load; Viral shedding