High levels of miR-146a-5p in COVID-19 patients are associated with Klebsiella lung coinfection.

BACKGROUND

Bacterial coinfections in COVID-19 patients present significant clinical challenges, particularly in severe cases. Previous studies have highlighted the role of microRNAs (miRNAs) in regulating immune responses, with miR-146a-5p and miR-21-5p implicated in inflammation and immune modulation. This study examines the effect of bacterial coinfections on the expression levels of these miRNAs in patients with severe COVID-19.

METHODS

We conducted a cohort study involving Mexican mestizo patients ≥18 years hospitalized with severe COVID-19, confirmed via PCR testing. Patients were categorized based on the presence or absence of bacterial coinfection, determined through bronchial aspirate or sputum culture. Blood samples were collected at admission and after 15 days of hospitalization to measure the relative expression levels of miR-146a-5p and miR-21-5p. Additionally, an in vitro assay was performed using peripheral blood mononuclear cells (PBMCs) exposed to stimuli (LPS, SARS-CoV-2 Spike Protein, and a combination of both).

RESULTS

Patients with bacterial coinfection were older (43 vs. 41 years, p = 0.046) and had a higher BMI than those without (29.40 vs. 27.51 kg/m2, p = 0.006). The PaO2/FiO2 ratio was significantly lower in co-infected patients (127.50 vs. 163.75 mmHg, p=0.002), who also exhibited higher rates of severe hypoxemia (35.2% vs. 8.7%), greater need for invasive mechanical ventilation (IMV, 96.0% vs. 34.7, p< 0.001), and higher mortality (80.3 vs. 13.0, p< 0.001). No significant differences in miRNA levels were noted after 15 days of hospitalization, regardless of bacterial presence. The in vitro assay did not reveal substantial differences in miRNA expression across stimuli. At the same time, Klebsiella spp. was identified as a predominant coinfecting pathogen, with significantly elevated levels of miR-146a-5p observed in these patients (p = 0.017).

CONCLUSIONS

Patients with COVID-19 and bacterial coinfection exhibit worse clinical indicators and increased disease severity, demonstrated by older age, higher BMI, severe hypoxemia, greater need for IMV, and increased mortality. Patients with COVID-19 and coinfection with Klebsiella spp. showed elevated levels of miR-146a-5p.