Skip to main content

Noninvasive sampling of the distal airspace via HME-filter fluid is not useful to detect SARS-CoV-2 in intubated patients

Sampling for SARS-CoV-2 is often carried out via bronchoscopy in intubated patients if upper respiratory samples at nasopharyngeal and oropharyngeal sites are negative or cannot be readily obtained [1]. PCR for detection of SARS-CoV-2 has been reported to have the highest sensitivity in lower respiratory tract samples [2]. Because bronchoscopy is an aerosol-generating procedure, alternative sampling methods with a similar sensitivity are of value. Previously, it has been demonstrated that heat moisture exchanger (HME) filter fluid had a composition approximating that of the fluid in the distal airspace (which is obtained during bronchoalveolar lavage) and can be used to test for pathogens [3,4,5].

The present investigation examined whether performing PCR for SARS-CoV-2 on unprocessed HME filter fluid is a viable method to test patients for infection instead of performing bronchoalveolar lavage via bronchoscopy.

Patients who had tested positive for SARS-CoV-2 and were treated with invasive ventilation for at least 12 h were enrolled prospectively (Fig. 1). The enrollment period was from May 2020 to December 2020. The initial test yielding the positive result was conducted using a nasopharyngeal swab.

Fig. 1
figure 1

Flowchart of study design

HME filters were swabbed with a regular swab on the septic side of the filter. The swabs were then placed in virus medium. SARS-CoV-2 PCR test systems used were either the BD MAX™ System with BioGX SARS-CoV-2 reagents (BD Life Sciences, Sparks, Maryland, USA) or the Hain Lifescience FluoroType® SARS-CoV-2 plus (Hain Lifescience GmbH, Nehren, Germany). Results of the tests of samples from the HME filters were compared with the results from the nasopharyngeal swab.

A sample size of 60 patients appeared to be adequate to compare the two different test methods. This report provides data for the initial 4 patients included in this prospective population.

Informed consent was acquired. If the patient was not able to provide informed consent, inclusion occured via an investigator consilium ("Giessener Lösung"). The ethics board of the state of Hessen, Germany, approved the study (AZ 79/20). The data collected from all patients were pseudonymized and entered into a database.

The trial was retrospectively registered on November 1st 2020 (DRKS registry; registration: DRKS00023494).

Four patients with positive nasopharyngeal swabs were enrolled in the study before an interim analysis of the results showed that it was unlikely that a sensitivity of greater than 90% would be reached. The enrollment was stopped prematurely. Of the 4 HME filter samples assayed, 3 did not test positive for SARS-CoV-2. All patients still tested positive in a bronchoalveolar lavage sample at a later point in time. Further results are provided in Table 1.

Table 1 Patient and testing data

Bronchoscopy with bronchoalveolar lavage is commonly used to test for SARS-CoV-2 in intubated patients. This study was designed to determine whether sampling HME filter fluid may present a feasible and safer alternative. Our preliminary data showed that HME filter fluid alone, without any additional processing, is not suitable for the detection of SARS-CoV-2 via PCR.

Given the manifest disease in the lung as observed in CT scans, a positive SARS-CoV-2 swab in the upper respiratory tract without the lungs being affected is unlikely in patients needing invasive ventilation. Hence, the reason for the negative results remain unclear.

Unfortunately, the study did not control for prior inhalation therapy. Some of the fluid could have been nebulized saline instead of precipitated moisture from the distal airspace carrying viral RNA. Even so, viral RNA should still be detectable under these conditions.

Further processing of the samples, including the extraction of more liquid via centrifugation of the HME filters, might yield better results, though processing steps would render the technique less applicable and appealing for widespread use [5].

Availability of data and materials

Data can be made available upon request.


  1. Wahidi MM, Lamb C, Murgu S, et al. American Association for Bronchology and Interventional Pulmonology (AABIP) statement on the use of bronchoscopy and respiratory specimen collection in patients with suspected or confirmed COVID-19 infection. J Bronchol Interv Pulmonol. 2020;27(4):e52–4.

    Article  Google Scholar 

  2. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323(18):1843–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. McNeil JB, Shaver CM, Kerchberger VE, et al. Novel method for noninvasive sampling of the distal airspace in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2018;197(8):1027–35.

    Article  CAS  Google Scholar 

  4. May AK, Brady JS, Romano-Keeler J, et al. A pilot study of the noninvasive assessment of the lung microbiota as a potential tool for the early diagnosis of ventilator-associated pneumonia. Chest. 2015;147(6):1494–502.

    Article  Google Scholar 

  5. Isaacs RJ, Debelak K, Norris PR, et al. Non-invasive detection of pulmonary pathogens in ventilator-circuit filters by PCR. Am J Transl Res. 2012;4(1):72–82.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


We thank Elizabeth Martinson, PhD, from the KHFI Editorial Office for her editorial assistance.


The study was funded by the local research institute (Kerckhoff Herzforschungsinstitut (KHFI)).

Author information

Authors and Affiliations



All authors were involved in the conception of the work, the interpretation of data as well as the drafting and revising the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Joerg Reifart.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the local ethics committee. All patients participated with consent.

Consent for publication

Does not apply since no identifying information is presented.

Competing interests

There are no financial or nonfinancial disclosures that could be construed as a conflict of interest in regard to this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reifart, J., Liebetrau, C., Troidl, C. et al. Noninvasive sampling of the distal airspace via HME-filter fluid is not useful to detect SARS-CoV-2 in intubated patients. Crit Care 25, 126 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: