Microbiota in COVID-19 Patients for Future Therapeutic and Preventive Approaches

Summary

In light of the rapidly emerging pandemic of SARS-CoV-2 infections, the global population and health care systems are facing unprecedented challenges through the combination of transmission and the potential for severe disease. Acute respiratory distress syndrome (ARDS) has been found with unusual clinical features dominated by substantial alveolar fluid load. It is unknown whether this is primarily caused by endothelial dysfunction leading to capillary leakage or direct virus induced damage. This knowledge gap is significant because the initial balance between fluid management and circulatory support appear to be decisive. On progression of the disease, bacterial superinfection facilitated by inflammation and virus related damage, has been identified as the main factor for patient outcome, but the role of the host versus the environment microbiome remains unclear.

The overarching aim of the present research proposal is to improve therapeutic strategies in critically ill patients with ARDS due to SARS-CoV-2 infection by advancing the pathophysiological understanding of this novel disease. This research thus focuses on inflammation, microcirculatory dysfunction and superinfection, aiming to elucidate risk factors (RF) for the development of severe ARDS in SARS-CoV-2 infected patients and contribute to the rationale for therapeutic strategies. The hypotheses are that (I) the primary damage to the lung in SARS-CoV-2 ARDS is mediated through an exaggerated pro-inflammatory response causing primary endothelial dysfunction, and subsequently acting two-fold on the degradation of the lung parenchyma - through the primary cytokine response, and through recruitment of the inflammatory-monocyte-lymphocyte-neutrophil axis. The pronounced inflammation and primary damage to the lung disrupts the pulmonary microbiome, leading secondarily to pulmonary superinfections. (II) Pulmonary bacterial superinfections are a significant cause of morbidity and mortality in COVID-19 patients. Pathogen colonization main Risk Factor for lower respiratory tract infections. To establish colonization, pathogens have to interact with the local microbiota (a.k.a. microbiome) and certain microbiome profiles will be more resistant to pathogen invasion. Finally, (III) Handheld devices used in clinical routine are a potential reservoir and carrier of both, SARS-CoV-2, as well as bacteria causing nosocomial pneumonia.

Conditions

• Corona Virus Infection
• ARDS
• Coinfection

Interventions

DIAGNOSTIC_TEST

Sampling (EDTA blood, pharyngeal and nose swabs, bronchoalveolar lavage ,urine)

Most data and part of the biological material required for addressing the research questions in this project are generated in the treatment of the patients. The following data and samples are collected specifically for this project according to the study schedule (i.e. extra sampling or additional questioning): * blood samples (day 0= 40 ml EDTA, day 2= 20 ml EDTA, day 3= 30 ml EDTA, day 5=10 ml EDTA, every 5 days = 20 ml EDTA) * Swabs (oral +/- nasal +/- nasopharyngeal) * Sublingual microscopy

Sponsors & Collaborators

• University of Zurich

  lead OTHER

Principal Investigators

• Silvio Brugger, SB · USZ

• Philipp K Buehler, PB · USZ

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-04-09

Primary Completion

2023-12-30

Completion

2023-12-31

Countries

• Switzerland

Study Locations