Incidence of VAP in Patients With Severe COVID-19

Study Overview
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Brief Summary
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Combined retrospective and prospective cohort study to evaluate the incidence of microbiologically confirmed VAP in mechanically ventilated patients with COVID-19. In the retrospective part, microbiological data are based on bi-weekly surveillance ETA. In the prospective part, microbiological data are based on ETA and BAL performed on VAP suspicion. In the prospective part, immunological and virological analyses will be performed on biological samples (blood, respiratory tract) collected from patients at VAP diagnosis.

Detailed Description
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Ventilator-associated pneumoniae (VAP) is the most common infection acquired in the intensive care unit (ICU). To date, there is no diagnostic gold standard for VAP, and its diagnosis is based on scores that include radiologic, clinical, laboratory, and microbiologic parameters. In addition, there is no univocal recommendation regarding the type of microbiological diagnostics. Some guidelines suggest the use of noninvasive methods (endotracheal aspiration, ETA) with semiquantitative cultures, while others suggest the collection of distal respiratory samples (bronchoalveolar lavage, BAL) with quantitative cultures. While the former method is characterized by higher sensitivity and lower specificity, the latter in contrast has higher specificity. To date, there is no evidence that one method is superior to the other in terms of clinical outcome. In patients with severe SARS-CoV-2 infection, COVID-19 disease itself and immunomodulatory therapies have a direct impact on most of the clinical, laboratory and radiologic parameters required to achieve VAP diagnosis. In this setting, a diagnostic approach characterized by higher sensitivity coupled with lower specificity could lead to of a high number of false positives. The greatest risk is that of an overdiagnosis of VAP and a consequent overtreatment, with the related therapeutic toxicity and increased antibiotic resistance. At the investigators' Hospital, the diagnosis of VAP is based on clinical-radiological suspicion according to the Johanson score (new finding or progression of infiltrates on lung radiography + at least two of the following three clinical criteria: fever > 38°C, leukocytosis or leukopenia, purulent secretions), widely validated in non-COVID patients. Until the end of 2020, microbiological data to confirm the diagnosis of clinically suspected VAP and to guide antibiotic therapy were based on the performance of biweekly surveillance ETA. In view of the limited specificity of this approach in COVID-19 setting, from the end of 2020 patients with SARS-CoV-2 infection and suspected VAP undergo, if clinically possible, to collection of distal respiratory specimens by performing BAL/mini-BAL. The present prospective-retrospective cohort study aims to evaluate the incidence of microbiologically confirmed VAP with BAL (prospective part) and biweekly surveillance ETA (retrospective part) in mechanically ventilated patients with COVID-19 in the ICU. In the prospective part, immunological and virological analyses will be performed on biological samples (blood, respiratory tract) collected from patients at VAP diagnosis. The study will last 12 months.

Official Title
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Cohort Study to Evaluate the Incidence of Ventilator-associated Pneumonia by Means of Bronchoalveolar Lavage in Patients With Severe SARS-CoV-2 Infection

Conditions
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Ventilator Associated Pneumonia, Covid19

Intervention / Treatment
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* Diagnostic Test: bronchoalveolar lavage


Participation Criteria
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Eligibility Criteria
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Retrospective part all patients admitted to the ICU for COVID-19-related respiratory failure since the beginning of the pandemics will be included. Prospective part Inclusion Criteria: Age ≥ 18 years Diagnosis of SARS-CoV-2 infection by means of reverse transcription polymerase chain reaction (RT-PCR) Respiratory failure requiring mechanical ventilation mechanical ventilation ongoing for less than 48h Exclusion Criteria: Age < 18 years mechanical ventilation ongoing for more than 48h

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VAP - BAL positive<br>Clinically suspected VAP, microbiologically confirmed by BAL | Diagnostic Test: bronchoalveolar lavage<br>* BAL and ETA are performed as per clinical practice on clinical suspicion of VAP (Johanson score)<br>|
| VAP - BAL negative<br>Clinically suspected VAP, not microbiologically confirmed by BAL | Diagnostic Test: bronchoalveolar lavage<br>* BAL and ETA are performed as per clinical practice on clinical suspicion of VAP (Johanson score)<br>|
| NO VAP<br>No clinically suspected VAP during mechanical ventilation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of VAP | Incidence of clinically suspected and microbiologically confirmed VAP by means of BAL | 1,000 ventilator days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of episodes with concordance in bacterial isolates between BAL and ETA performed on VAP suspicion | microbiological concordance of respiratory specimens collected by BAL and ETA on VAP suspicion | 1,000 ventilator days | 
| number of episodes with concordance in bacterial isolates between BAL performed on VAP suspicion and the preceding surveillance ETA | microbiological concordance of respiratory specimens collected by BAL on VAP suspicion and the preceding bi-weekly surveillance ETA | 1,000 ventilator days | 
| number of episodes with concordance in cellular phenotype between BAL and peripheral blood on VAP suspicion | immunological analysis of cellular phenotype in BAL and peripheral blood collected on VAP suspicion | 1,000 ventilator days | 
| number of episodes with concordance in lymphocyte-monocyte activation between BAL and peripheral blood on VAP suspicion | immunological analysis of lymphocyte-monocyte activation in BAL and peripheral blood collected on VAP suspicion | 1,000 ventilator days | 
| number of episodes with concordance in SARS-CoV-2 viral quantification between BAL, ETA and nasopharyngeal swab on VAP suspicion | virological analysis of SARS-CoV-2 viral quantification in BAL, ETA and nasopharyngeal swab collected on VAP suspicion (subgroup analysis) | 1,000 ventilator days | 
| number of episodes with concordance in SARS-CoV-2 sequencing between BAL, ETA and nasopharyngeal swab on VAP suspicion | virological analysis of SARS-CoV-2 sequencing in BAL, ETA and nasopharyngeal swab collected on VAP suspicion (subgroup analysis) | 1,000 ventilator days |