A host transcriptomic signature for identification of respiratory viral infections in the community

Eur J Clin Invest. 2021 Dec;51(12):e13626. doi: 10.1111/eci.13626. Epub 2021 Jun 13.

Abstract

Background: Fever-7 is a test evaluating host mRNA expression levels of IFI27, JUP, LAX, HK3, TNIP1, GPAA1 and CTSB in blood able to detect viral infections. This test has been validated mostly in hospital settings. Here we have evaluated Fever-7 to identify the presence of respiratory viral infections in a Community Health Center.

Methods: A prospective study was conducted in the "Servicio de Urgencias de Atención Primaria" in Salamanca, Spain. Patients with clinical signs of respiratory infection and at least one point in the National Early Warning Score were recruited. Fever-7 mRNAs were profiled on a Nanostring nCounter® SPRINT instrument from blood collected upon patient enrolment. Viral diagnosis was performed on nasopharyngeal aspirates (NPAs) using the Biofire-RP2 panel.

Results: A respiratory virus was detected in the NPAs of 66 of the 100 patients enrolled. Median National Early Warning Score was 7 in the group with no virus detected and 6.5 in the group with a respiratory viral infection (P > .05). The Fever-7 score yielded an overall AUC of 0.81 to predict a positive viral syndromic test. The optimal operating point for the Fever-7 score yielded a sensitivity of 82% with a specificity of 71%. Multivariate analysis showed that Fever-7 was a robust marker of viral infection independently of age, sex, major comorbidities and disease severity at presentation (OR [CI95%], 3.73 [2.14-6.51], P < .001).

Conclusions: Fever-7 is a promising host immune mRNA signature for the early identification of a respiratory viral infection in the community.

Keywords: community; expression; gene; infection; respiratory; viral.

Publication types

  • Observational Study

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Aged
  • Aged, 80 and over
  • Cathepsin B / genetics
  • DNA-Binding Proteins / genetics
  • Early Warning Score
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / genetics
  • Nasopharynx / virology
  • RNA, Messenger / blood*
  • Respiratory Tract Infections / blood
  • Respiratory Tract Infections / diagnosis*
  • Respiratory Tract Infections / genetics
  • Transcriptome
  • Virus Diseases / blood
  • Virus Diseases / diagnosis*
  • Virus Diseases / genetics
  • gamma Catenin / genetics

Substances

  • Adaptor Proteins, Vesicular Transport
  • DNA-Binding Proteins
  • GPAA1 protein, human
  • IFI27 protein, human
  • JUP protein, human
  • LAX1 protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • TNIP1 protein, human
  • gamma Catenin
  • CTSB protein, human
  • Cathepsin B