COVID-19 pandemic has shed light on the risk of shortage in ICU beds related to the surge of ICU admissions, but also to prolonged bed occupancy by patients with sustained respiratory failure. Protracted mechanical ventilation in SARS-CoV-2 pneumonia can be primarily ascribed to the severity of the lung injury, but also to the development of secondary complications. In this study, we addressed the specific risk of ICU-acquired pneumonia in the course of severe. When compared to recent cohorts of patients with non-COVID-19 pneumonia, patients with severe SARS-CoV-2 pulmonary infection exhibited a prominent risk of ICU-acquired pneumonia.
Other studies have already reported various frequency rates of ICU-acquired pneumonia in mechanically ventilated COVID-19 patients, with estimated incidence ranging from 16 to 31% in two early reports from China [11, 12]. Since then, several studies confirmed this impression [13,14,15,16]. Importantly, an accurate estimation for the cumulative risk of ICU-acquired pneumonia in ventilated patient requires handling two main competing events that are extubation and death to avoid misinterpretation of risks. The high rate of ICU-acquired pneumonia in COVID-19 patients may result from a particular susceptibility to pulmonary superinfections. The question is whether COVID-19 stands as risk factor of ICU-acquired infections on its own, or if this association is rather related to confounding factors such as exposure to invasive devices or significant changes in care practice. Such a retrospective study can hardly provide a definite answer between causality and association, despite investigating the potential confounders and entering them into multivariate models. Since ICU-acquired pneumonia is strongly associated with the duration under invasive mechanical ventilation, we treated mechanical ventilation as a time-dependent covariate in multivariate analysis [17]. Nonetheless, it is noteworthy that times from intubation to the first episode of ICU-acquired pneumonia were similar across the three groups. Of note, nearly all patients from the three groups had received antibiotics in the early days in the ICU. The increased risk of ICU-acquired pneumonia may also be related to increased workload that may have prevented strict and thorough implementation of preventive bundles.
COVID-19 has emerged as a particular infection with a characteristic two-step course in a significant proportion of patients. Whereas the primary symptoms are associated with viral shedding, secondary respiratory deterioration is associated with potent systemic acute inflammatory response. The pathophysiology of COVID-19 lung involvement encompasses endothelial and epithelial alterations as well as pulmonary embolism and microvascular thrombosis. Besides, secondary infectious insults sustain acute lung injury and likely contribute to prolonged mechanical ventilation. The particular susceptibility of post-COVID critically ill patients to ICU-acquired pneumonia suggests defective anti-infective immune responses against bacterial superinfections reminiscent of those observed in post-septic patients [18]. Sepsis-induced immunosuppressive response is related to various quantitative and functional alterations in most immune cells [4]. Whether such immune dysfunctions may also account for increased susceptibility to secondary infections in COVID-19 patients remains to be investigated.
Interventional studies for severe COVID-19 have so far attempted dampening the primary pro-inflammatory cytokine response by anti-inflammatory compounds, most especially to prevent the respiratory deterioration of patients with mild pneumonia. There is no signal so far that such early immunomodulatory therapeutics of COVID-19 may increase the risk of secondary infections. However, the particular susceptibility of COVID-19 patients to secondary bacterial infections raises the question of immunostimulant strategies later on in the ICU. For instance, drugs known to restore monocyte functions and HLA-DR and CD14 expressions such as interferon gamma (IFNγ) or GM-CSF, or drugs to restore lymphocyte activation such as IL-7 or thymosin-α may represent attractive therapeutic options in this setting [19].
This study has several limitations. Although improving the external validity, the multicentre design also harbours the risk of inconsistent care and diagnostic procedures. The diagnosis of ICU-acquired pneumonia was let at the discretion of the physician in charge, with the help of a validated score, and was reviewed by an independent investigator to ensure appropriate and consistent diagnosis. Data from severe COVID-19 patients were obtained from seven different ICUs, whereas controls with bacterial and viral pneumonia were obtained from one single centre. However, frequencies of secondary pneumonia in COVID-19 patients were consistent across centres, and the centre effect was taken into account in the multivariate models. Most importantly, such a retrospective study is limited to establish a definite causality inference, although we aimed at taking into account major determinants of ICU-acquired pneumonia in the multivariate model.