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Original research
Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia
  1. Samir Gautam1,
  2. Avi J Cohen1,
  3. Yannick Stahl1,
  4. Patricia Valda Toro1,
  5. Grant M Young1,
  6. Rupak Datta2,
  7. Xiting Yan1,
  8. Nicholas T Ristic1,
  9. Santos D Bermejo1,
  10. Lokesh Sharma1,
  11. Marcos I Restrepo3,4,
  12. Charles S Dela Cruz1
  1. 1Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
  2. 2Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
  3. 3Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health, San Antonio, Texas, USA
  4. 4Section of Pulmonary & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, USA
  1. Correspondence to Dr Charles S Dela Cruz, Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA; charles.delacruz{at}yale.edu

Abstract

Introduction Procalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis.

Methods We conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection.

Results Patients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p<0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dropped substantially, from 72% to 61%. In fact, receiver operating characteristic curve analysis showed that procalcitonin was a better indicator of multiple indices of severity (eg, organ failures and mortality) than of coinfection. Accordingly, patients with severe viral infection had elevated procalcitonin. In murine and cellular models of influenza infection, procalcitonin was also elevated despite bacteriologic sterility and correlated with markers of severity. Interferon signalling did not abrogate procalcitonin synthesis.

Discussion These studies reveal that procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.

  • Bacterial Infection
  • Pneumonia
  • Respiratory Infection
  • Viral infection
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Footnotes

  • AJC, YS, PVT and GMY contributed equally.

  • Correction notice This article has been corrected since it was published Online First. A middle initial was added to Marcos Restrepo and a second affiliation was also added.

  • Contributors All author have made meaningful intellectual contributions to the work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by Yale’s institutional review board (approval #2000023067).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Deidentified patient data are available on request made to CSDC, charles.delacruz@yale.edu.

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