Microorganisms (Sep 2021)

Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study

  • Erica Franceschini,
  • Alessandro Cozzi-Lepri,
  • Antonella Santoro,
  • Erica Bacca,
  • Guido Lancellotti,
  • Marianna Menozzi,
  • William Gennari,
  • Marianna Meschiari,
  • Andrea Bedini,
  • Gabriella Orlando,
  • Cinzia Puzzolante,
  • Margherita Digaetano,
  • Jovana Milic,
  • Mauro Codeluppi,
  • Monica Pecorari,
  • Federica Carli,
  • Gianluca Cuomo,
  • Gaetano Alfano,
  • Luca Corradi,
  • Roberto Tonelli,
  • Nicola De Maria,
  • Stefano Busani,
  • Emanuela Biagioni,
  • Irene Coloretti,
  • Giovanni Guaraldi,
  • Mario Sarti,
  • Mario Luppi,
  • Enrico Clini,
  • Massimo Girardis,
  • Inge C. Gyssens,
  • Cristina Mussini

DOI
https://doi.org/10.3390/microorganisms9091896
Journal volume & issue
Vol. 9, no. 9
p. 1896

Abstract

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Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care units were published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: we conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs. 49.0%, p = 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs. 22.4%, p = 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with the use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR = 5.13, 95% CI:1.36–19.32, p = 0.016). The effect size was larger when restricting to participants who were treated with high doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.

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