False-positive Legionella pneumophila antibodies in COVID-19 patients

Dear Editor,

The number of patients with coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased in China since the reopening. From December 30, 2022, to January 30, 2023, a total of 23 critically ill patients with COVID-19 were consecutively admitted to a medical intensive care unit of Peking Union Medical College Hospital. We detected Immunoglobulin M (IgM) of Legionella pneumophila (LP) serological antibody test in 14 (14/23, 60.9%) patients. However, the subsequently confirmative investigation of both Polymerase chain reaction (PCR) (14/14, 100%) from bronchoalveolar fluid (BALF) and urine antigen test (12/12, 100%) for LP were negative.

As shown in Fig. 1A, the characteristics and managements were similar between LP-IgM positive and negative groups. Meanwhile, the PCR cycle threshold (C_t) value (30.6 ± 4.8 vs. 26.2 ± 4.3, p < 0.05) and IgM titers (2.1 ± 2.8 vs. 0.3 ± 0.6, P < 0.05) of SARS-CoV-2 in LP-IgM positive group was higher than negative group (B).

Fig. 1

False-positive Legionella pneumophila antibodies in COVID-19 patients A shows the comparison of demographic and clinical characteristics of the enrolled patients between two groups.  B shows the difference of IgM titers of SARS-CoV-2 between two groups. ^†Plus–minus values are means ± standard deviation. ^‡The categorical variables were compared using the Chi squared test or Fisher’s exact test. The continuous variables were compared using the Mann–Whitney U test or t test. A two-sided α of less than 0.05 was considered statistically significant. *Patients who received corticosteroids on the day of LP-IgM testing (prednisone equivalent dose). IgM Immunoglobulin M, LP Legionella pneumophila, APACHE Acute Physiology and Chronic Health Evaluation, COPD Chronic obstructive pulmonary disease, C_t cycle threshold, hsCRP High-sensitivity C-reactive protein

Recent studies showed that the incidence of COVID-19 co-infection with LP ranged from 0.288–1.1% [1, 2] based on PCR from lower respiratory tract specimens or urine antigen testing, to 12.6–20% [3, 4]  based on immune-fluorescence or ELISA serological antibody test. To our knowledge, our study was the first report to confirm false-positive LP-IgM in COVID-19, which was similar to the cross-immune responses in previous studies [5].

Considering the potential risk of false positive results in COVID-19 patients, we suggest avoiding the immediate testing of LP-IgM or diagnosing Legionella pneumophila infection. Similarly, we advise against the empirical use of antibiotics such as fluoroquinolones. Instead, we recommend testing respiratory secretions DNA or urine Legionella pneumophila antigen for accurate diagnosis and appropriate treatment. Given the decrease in the incidence of COVID-19, the disease has become a crucial differential diagnosis, highlighting the significance of identifying patients who are admitted to the ICU with COVID-19. Our findings suggest a high positivity rate of LP-IgM in COVID-19 patients, which could serve as a potential risk factor. Therefore, clinicians should consider conducting SARS-CoV-2 testing in LP-IgM-positive patients.