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Diagnosis of Legionnaires' Disease Assisted by Next-Generation Sequencing in a Patient with COVID-19
Po-Hsiu Huang1, Yao-Ting Huang2, Po-Hsin Lee3,4,5,6
1Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Abstract:
Coinfection in COVID-19 patients is associated with worsening outcome. Among patients with COVID-19, Legionella pneumophila, a common cause of pneumonia, has been reported as a co-occurring respiratory infection. A nonspecific clinical presentation, however, makes an early diagnosis difficult. Bronchoalveolar lavage fluid was collected from a patient suffering from COVID-19 and presenting with pneumonia and sent for metagenomic analysis. Differential abundance analysis was carried out by comparing each taxon reads per million between the bronchoalveolar lavage fluid sample and the negative control. Two replicates of metagenomic sequencing were conducted on bronchoalveolar lavage fluid samples. Within each replicated sequencing, one negative control was sequenced for comparison of taxon abundance in the BALF sample. In both replicates, Legionella pneumophila was the only taxon with significantly higher abundance when compared with the negative control. PCR of the bronchoalveolar further confirmed the presence of L. pneumophila. Several studies have estimated that the incidence of Legionnaires' disease co-infection in patients with COVID-19 infection is approximately 0% to 1.5%. There are some common characteristics of COVID-19 and co-infection with Legionnaires' disease, making it difficult to diagnose bacterial infection early. The diagnosis of these cases is important due to the different treatments used. Current diagnostic tests for Legionnaires' disease include conventional culture, urinary antigen for L. pneumophila serogroup 1, polymerase chain reaction, direct fluorescent antibody stain, and paired serology. The current study demonstrated that metagenomics is a promising approach that facilitated the diagnosis of Legionnaires' disease.
Insights
Coinfection with Legionnaires
Area of Science:
- Infectious Diseases
- Microbiology
- Genomics
Background:
- Coinfection in COVID-19 patients can lead to severe outcomes.
- Legionella pneumophila, a cause of Legionnaires' disease, is a potential coinfecting agent.
- Nonspecific symptoms of COVID-19 and Legionnaires' disease complicate early diagnosis.
Purpose of the Study:
- To investigate the utility of metagenomic analysis in diagnosing Legionnaires' disease coinfection in a COVID-19 patient.
- To highlight the diagnostic challenges and importance of identifying bacterial coinfections.
Main Methods:
- Bronchoalveolar lavage fluid was collected from a COVID-19 patient with pneumonia.
- Metagenomic sequencing and differential abundance analysis were performed.
- Polymerase chain reaction (PCR) was used for confirmation.
Main Results:
- Metagenomic analysis revealed significantly higher abundance of Legionella pneumophila in the patient's sample compared to controls.
- PCR confirmed the presence of L. pneumophila.
- The study identified metagenomics as a promising diagnostic tool.
Conclusions:
- Metagenomic sequencing facilitates the diagnosis of Legionnaires' disease coinfection in COVID-19 patients.
- Early and accurate diagnosis is crucial for appropriate treatment of coinfections.
- This approach aids in differentiating bacterial infections from viral ones.

