Ventilator-associated lower respiratory tract infections (VA-LRTI) still remain one of the most common complications during invasive mechanical ventilation associated with increased duration of mechanical ventilation and ICU stay. By definition, they encompass both ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), the last associated with increased mortality and healthcare cost. Particularly, during the ongoing SARS-CoV-2 pandemic, a significant number of patients require invasive mechanical ventilation (10% of hospitalized patients) and therefore threatened by increased risk for VA-LRTI. However, even though the huge research efforts about SARS-CoV-2 disease (COVID-19), data about the epidemiology of these infections are still lacking or conflicting.
In this context, the European multicenter retrospective observational study by Anahita Rouzé and colleagues makes an important contribution investigating the impact of SARS-CoV-2 infection on the incidence of VA-LRT (1). Principal aim of the study was to investigate the incidence of VA-LRTI among ICU patients with SARS-CoV-2 infection, as compared to two control groups (influenza and no viral infection groups). The large sample size (1546 included patients), the multicentric research (36 ICUs in Europe), the rigorous applied methodology and the right study design, made the study one of the first impacting research specifically addressed on this topic. Main result from the paper was that the incidence of VA-LRTI was significantly higher in SARS-CoV-2 pneumonia group (50.5%) than in the other groups (influenza 30.3% and no viral infection 25.3%), also when adjusted for all the confounding factors (adjusted HR 1.60 [1.26-2.04] for influenza group and 1.70 [1.2-2.39] for no-viral infection group). Gram-negative bacilli were main etiological agents for VA-LRTI. Interestingly, the interpretation of these results could open further discussion about the disease itself, from the prevention measures up to its physiopathology.

• In particular for VAP, the incidence is reported around 5-40% in the previous studies regardless the underlying cause, with great differences in the VAP definition, the study design and population (2). These data were substantially confirmed by Rouzé et al., who indicate a VAP incidence about 36,1%. Surprisingly, the authors reported VAP incidence significantly higher in SARS‐CoV‐2 group when compared with the other two groups (adjusted HR 1.57 [1.2-2.04] SARS‐CoV‐2 vs. influenza; adjusted HR 1.84 [1.26-2.7] SARS‐CoV‐2 vs. no viral infection). As suggested by the authors itself, these results could be partly explained by longer duration of mechanical ventilation and higher incidence of ARDS, independent risk factors for VAP (3). In addition, other variables like higher duration and doses of corticosteroids could aid to explain these results.
  On the contrary, patients in the three groups did not differ in their previous chronic disease. More surprisingly, the SARS‐CoV‐2 patients were less previously affected by COPD, chronic respiratory failure and active smoking, well known risk factors for VAP (2). Even though further studies are required, one could argue the pathophysiological peculiarities of the SARS‐CoV‐2 infection could made patients more prone to the VAP: the formation of hyaline membranes and edema on the alveolar side, the coagulation activation and thrombi formation on the vascular side could further local bacterial colonization and thus lung infection (4).
• Gram‐negative bacilli (Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp.) were the main etiological agents for VA‐LRTI, as reported in the previous studies. Interestingly, the occurrence of MDR-agents was lower in SARS-CoV-2 patients. Even if these results cannot be generalized in a broader context as the incidence of MDR-agents differs in the various countries, variables like lower rate of recent hospitalizations and previous use of antibiotics could explain these results. Thus, it easy to recognize how the prevention measures and the proper use of antibiotic therapy regardless the pandemic context could impact on ICU patients.

Nevertheless, VA-LRTI still remains a major complication for critically ill patients, even more during the ongoing pandemic due to the great amount of mechanically ventilated patients. The present study clarifies some aspect of this topic, but some aspects, like diagnosis criteria, antimicrobial therapy and treatment delay still remain challenging. Ultrasound could be of help in the early detection of VAP at the bedside (5) in this particular population since obtaining distal microbiological is a procedure at high risk of contamination and traditional imaging increases the number of exposed healthcare providers.

References

1. Rouzé A, Martin-Loeches I, Povoa P, et al. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med DOI:10.1007/s00134-020-06323-9.
2. Papazian L, Klompas M, Luyt CE. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med 2020;46:888-906.
3. Forel JM, Voillet F, Pulina D, et al. Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy. Crit Care 2012;16. DOI:10.1186/cc11312.
4. Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA - J Am Med Assoc 2020;2019:1-13.
5. Mongodi S, Via G, Girard M, et al. Lung ultrasound for early diagnosis of ventilator-associated pneumonia. Chest 2016;149:969-80.