Evidence map›Paper›PMID 41928312›Full record

ArticleCritical care (London, England)2026

Histological proof of pulmonary herpesvirus presence in patients with COVID-19- or influenza-related ARDS.

Jannes Heylen, Boaz Lopuhaä, Lore Vanderbeke, Simon Feys, Lenn Maessen, Cato Jacobs, Hanne Moon Lauwers, Kurt Beuselinck, Greet De Vlieger, Laurens De Sadeleer and 14 more

Abstract read
In one paragraph

Article in Critical care (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Jannes Heylen *Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. jannes.heylen@uzleuven.be.
Boaz Lopuhaä *Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, Netherlands.
Lore VanderbekeDepartment of Infectious Diseases, Hospital AZORG, Aalst, Belgium.
Simon FeysDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Lenn MaessenDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Cato JacobsMedical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Herestraat 49, Box 7003 04, Leuven, 3000, Belgium.
Hanne Moon LauwersMedical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Herestraat 49, Box 7003 04, Leuven, 3000, Belgium.
Kurt BeuselinckDepartment of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium.
Greet De VliegerLaboratory and Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium.
Laurens De SadeleerDepartment of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
Greet HermansMedical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Herestraat 49, Box 7003 04, Leuven, 3000, Belgium.
Katrien LagrouDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Philippe MeerssemanDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Wouter MeerssemanDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Marijke PeetermansDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Eric Van WijngaerdenDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Alexander WilmerDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Georges M VerjansDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
Thierry P P van den BoschDepartment of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, Netherlands.
Jan H von der ThüsenDepartment of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, Netherlands.
Gert De HertoghDepartment of Translational Cell & Tissue Research, KU Leuven, Leuven, Belgium.
Jeroen J A van Kampen *Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
Joost Wauters *Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
OPPORTUNE consortium

Funding

Fonds Wetenschappelijk Onderzoek 11PBR24NZonMw 10430102110011
6 · The paper itself

Abstract

backgroundHerpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV) are frequently detected in respiratory samples from patients with acute respiratory distress syndrome (ARDS), yet whether PCR positivity reflects histologically confirmed pulmonary infection and contributes to lung injury remains unclear. We aimed to characterize the histopathological features of pulmonary HSV-1 and CMV using PCR and immunohistochemistry on lung tissue specimens of critically ill patients with influenza- or COVID-19-related ARDS obtained at autopsy. In addition, we sought to correlate pulmonary herpesvirus loads in antemortem bronchoalveolar lavage fluid (BALF) samples with postmortem histological findings.

methodsIn this retrospective autopsy cohort, we included patients with COVID-19- or influenza-related ARDS who died in the intensive care unit and underwent autopsy between 2009 and 2021. Lung tissue blocks were systematically screened for HSV-1 and CMV using PCR and immunohistochemistry. Performance of HSV-1 PCR on BALF for diagnosing proven HSV-1 infection was evaluated with receiver operating characteristic analysis.

resultsWe included 22 patients with COVID-19- and 20 with influenza-related ARDS. Proven HSV-1-associated necrotizing tracheobronchitis was identified in 6/42 patients (14%). Proven CMV infection was identified in only one patient, displaying focal presence of a few CMV-infected cells. An optimal cutoff of 4.11 log₁₀ copies/mL for HSV-1 in BALF yielded 100% sensitivity and 69% specificity for diagnosis of proven HSV-1 infection.

conclusionsPulmonary HSV-1 was associated with tracheobronchitis in a subset of patients in a viral load dependent manner. Pulmonary CMV presence appeared histologically insignificant and likely represents a bystander phenomenon of critical illness.

Indexed as

COVID-19Influenza, HumanRespiratory Distress SyndromeAgedAutopsyBronchoalveolar Lavage FluidFemaleHumansMaleMiddle AgedRetrospective StudiesARDSCOVID-19CytomegalovirusHerpes simplex virus type 1Influenza

Identifiers

PMID41928312
PMCPMC13123176

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.