Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000-2016

Ann-Brit E Hansen; Hanne T Vestergaard; Ram B Dessau; Jacob Bodilsen; Nanna S Andersen; Lars H Omland; Claus B Christiansen; Svend Ellermann-Eriksen; Lene Nielsen; Thomas Benfield; Henrik T Sørensen; Christian Ø Andersen; Anne-Mette Lebech; Niels Obel

doi:10.2147/CLEP.S256838

Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000-2016

Clin Epidemiol. 2020 Jul 16:12:745-755. doi: 10.2147/CLEP.S256838. eCollection 2020.

Authors

Ann-Brit E Hansen^{1

2

3}, Hanne T Vestergaard⁴, Ram B Dessau⁵, Jacob Bodilsen⁶, Nanna S Andersen⁷, Lars H Omland¹, Claus B Christiansen⁸, Svend Ellermann-Eriksen⁹, Lene Nielsen¹⁰, Thomas Benfield^{2

3}, Henrik T Sørensen¹¹, Christian Ø Andersen¹², Anne-Mette Lebech^{1

3}, Niels Obel^{1

3}

Affiliations

¹ Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
² Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
³ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Virus & Microbiological Special Diagnostics, Statens Serum Institute, Copenhagen, Denmark.
⁵ Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark.
⁶ Departments of Infectious Diseases and Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.
⁷ Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark.
⁸ Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁹ Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
¹⁰ Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
¹¹ Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
¹² Department of Clinical Microbiology, Amager Hvidovre University Hospital, University of Copenhagen, Hvidovre, Denmark.

Abstract

Background: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated.

Patients and methods: We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830).

Results: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (-0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference -19.8%; 95% CI: -34.7% to -4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: -0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4).

Conclusion: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.

Keywords: cohort study; herpes simplex virus encephalitis; herpes simplex virus meningitis; outcome; prognosis.

Grants and funding

The study was supported by the Danish Council for Independent Research, grant number: [6110-00173B]. The sponsor had no influence on the preparation, design, analysis, or reporting of this study.