Tracheobronchial reactivation of HSV-1 is a common finding in critically ill patients and is associated with longer intensive care unit (ICU) stay and mechanical ventilation. At present it is unclear whether the presence of HSV-1 reactivation can be predicted by the clinical phenotype. In the present study, the performance of a bronchoscopic score of tracheobronchial inflammation for prediction of tracheobronchial HSV-1 reactivation is investigated

Critically ill adult patients having a first diagnostic or therapeutic bronchoscopy are included. A standardized bronchoscopic score (values from 0 to 6) is assessed by an experienced ICU physician.

The score compounds are mucosal redness, mucosal swelling and vulnerability on contact. Compounds are quantified as "none" = 0, "some, disseminated" = 1, or "profound, ubiquitous" = 2 and added.

HSV-1 reactivation is detected by quantitative polymerase chain reaction (PCR) analysis of HSV-1-DNA from standardized bronchoalveolar lavage fluid.

In addition, HSV-1-DNA from blood and markers of immunocompetence (lymphocyte subtype count, monocyte count and Human Leukocyte Antigen - DR isotype (HLA-DR) expression, immunoglobulins) are measured for secondary analyses.

Inclusion Criteria:

• 1. Adult patients (age ≥18 years) 2. Indication for bronchoscopy during intensive care unit stay 3. Written informed consent

Exclusion Criteria:

• 1. Solid organ transplantation 2. Present coronavirus disease 2019 (COVID-19) infection 3. Previous bronchoscopy during present hospital stay 4. Pregnancy 5. Known primary or secondary severe immunodeficiency

Critically ill patients