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Observational Study
. 2021 Dec 6;25(1):417.
doi: 10.1186/s13054-021-03843-8.

HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients

Antoine Meyer  1   2 , Niccolò Buetti  3   4 , Nadhira Houhou-Fidouh  5 , Juliette Patrier  2 , Moustafa Abdel-Nabey  2 , Pierre Jaquet  2 , Simona Presente  2 , Tiphaine Girard  2 , Faiza Sayagh  2 , Stephane Ruckly  1   2 , Paul-Henri Wicky  2 , Etienne de Montmollin  1   2 , Lila Bouadma  1   2 , Romain Sonneville  2   6 , Diane Descamps  7 , Jean-Francois Timsit  1   2
Affiliations
Observational Study

HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients

Antoine Meyer et al. Crit Care. .

Abstract

Background: Data in the literature about HSV reactivation in COVID-19 patients are scarce, and the association between HSV-1 reactivation and mortality remains to be determined. Our objectives were to evaluate the impact of Herpes simplex virus (HSV) reactivation in patients with severe SARS-CoV-2 infections primarily on mortality, and secondarily on hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and intensive care unit-bloodstream infection (ICU-BSI).

Methods: We conducted an observational study using prospectively collected data and HSV-1 blood and respiratory samples from all critically ill COVID-19 patients in a large reference center who underwent HSV tests. Using multivariable Cox and cause-specific (cs) models, we investigated the association between HSV reactivation and mortality or healthcare-associated infections.

Results: Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation (19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples. Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001). After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk (hazard risk [HR] 2.05; 95% CI 1.16-3.62; p = 0.01). HAP/VAP occurred in 67/153 (43.8%) and ICU-BSI in 42/153 (27.5%) patients. In patients with HSV-1 reactivation, multivariable cause-specific models showed an increased risk of HAP/VAP (csHR 2.38, 95% CI 1.06-5.39, p = 0.037), but not of ICU-BSI.

Conclusions: HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and HAP/VAP.

Keywords: Bacteremia; COVID-19; Critically ill; HSV; Mortality; Pneumonia.

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Conflict of interest statement

The authors have disclosed that they do not have conflict of interest. JFT received fees for lectures to 3M, MSD, Pfizer, and Biomerieux. JFT received research grants from Astellas, 3M, MSD, and Pfizer. JFT participated to advisory boards of 3M, MSD, Bayer Pharma, Nabriva, and Pfizer.

Figures

Fig. 1
Fig. 1
Flowchart. HSV Herpes simplex virus. PCR polymerase chain reaction
Fig. 2
Fig. 2
Association between HSV-1 reactivation and mortality at day 60. HSV Herpes simplex virus; SOFA Sequential Organ Failure Assessment
Fig. 3
Fig. 3
Association between HSV detection and nosocomial infections (hospital acquired pneumonia/ventilator associated pneumonia and bacteremia). NB: Adjustment factors were age, chronic disease, extra-respiratory SOFA score, type of ventilation, use of corticosteroids. To avoid overfitting with mechanical ventilation variables, only extra-respiratory components of SOFA score were taken into account. SOFA Sequential Organ Failure Assessment
See this image and copyright information in PMC

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