Nasopharyngeal Microbiota and the Host ACE2 in COVID-19

What is the COVID-19 symptom onset and severity? We search for the answer in this study about the role of the nasopharyngeal microbiota and the host ACE2 receptor in the pediatric and adult population

Have your heard about the ACE2 receptor?

The angiotensin-converting enzyme 2 (ACE2) receptor acts as the receptor-binding domain for the SARS-CoV-2 virus Spike complex. This permits viral attachment, fusion and intracellular entry and infection with COVID-19. SARS-CoV-2 enters lung cells via this receptor. In this study, we will analyze the role of the ACE2 receptor and the nasopharyngeal microbiota in combating COVID-19.

Ace2 Receptor
The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.

Description of the Study:

  • Title: COVID-19 Onset and Severity in Children and Adults: Role of the Nasopharyngeal Microbiota and the Host ACE2 Receptor.
  • Principal investigator: Pedro Brotons and Cristian Launes.
  • Co-investigators: Carmen Muñoz-Almagro, Iolanda Jordán, Victoria Fumadó and Desiré Henares.
  • Centers of implementation: Hospital Sant Joan de Déu de Barcelona (HSJD), Hospital Universitari Mútua de Terrassa (HUMT), Fundació per al Foment de la Investigació Biomèdica de la Comunitat València (FISABIO) and Universitat Internacional de Catalunya (UIC).
  • Study Population:
    i. Objective 1: In cases cohorts, children aged ≤ 18 years old attended in HSJD and PCR-positive for HCoV. In control cohorts, children aged ≤ 18 years attended in HSJD and PCR-negative for HCoV.
    ii. Objective 2 – 4: In cases cohorts, subjects with clinical symptoms of COVID-19 (cough, dyspnea, fever, fatigue) and PCR-positive for SARS-CoV-2, attended in HSJD (children aged ≤ 18 years) and HUMT (adults aged ≥ 19 years). In control cohorts, subjects with clinical suspicion of COVID-19 and PCR result negative for SARS-CoV-2 obtained within 7 days since first symptom onset. Serological tests should also be negative in case of test request by pediatricians.
  • Study Type:
    i. Objective 1: Single-center retrospective case-control study
    ii. Objective 2 – 4: Multi-center prospective case-control study
  • Design:
    i. Objective 1: The study will be implemented in children. The cases and controls frequency-matched by age, sex, and time of sampling.
    ii. Objective 2 – 4: The study will be implemented in children and adults. The cases and controls matched by age, sex, and time of sampling.
  • Methods:
    i. Objective 1: Nasopharyngeal aspirates representative of severe low respiratory infection (n = 150), mild upper respiratory infection (n = 150), and asymptomatic carriage and healthy status (n = 55).
    ii. Objective 2 – 4:
    – Nasopharyngeal aspirates (participants aged ≤ 18 years) and swabs (participants aged ≥ 19 years) from all cases and controls at study entry.
    – Bronchoalveolar lavages from severe COVID-19 cases admitted to the ICU.
    – Saliva samples collected with oral swabs and/or tracheal aspirates from severe COVID-19 cases at recruitment, at day 7, and at date of hospital discharge.

Objectives of the Study:

Principal Objective: The overall aim of this study is to determine the implications of the nasopharyngeal microbiota and the ACE2 receptor in COVID-19 onset and severity in children and adults.
(1) To compare composition, richness and diversity of nasopharyngeal microbiota in children across 3 respiratory states: severe low respiratory infection (caused by HCoV vs non-HCoV), mild upper respiratory infection (caused by HCoV vs non-HCoV), and asymptomatic infection (caused by HCoV vs non-HCoV) or healthy state.
(2) To compare composition, richness and diversity of nasopharyngeal microbiota in children and adults with COVID-19 confirmed by PCR and patients suspected of COVID-19 but PCR-negative.
(3) To assess the value of ACE2 quantified by western blot in saliva samples as a prognostic marker of COVID-19 severity and compare ELISA-based ACE2 and western blot quantification in saliva of COVID-19 patients.
(4) To describe and compare COVID-19 clinical presentations in children and adults, and determine epidemiological and molecular prognostic factors for COVID-19 severity in the two groups.

More about this Study:

Kids Corona: The Kids Corona platform, which the San Joan de Déu Hospital launched last April continues to offer answers to better understand the incidence, impact, and transmission capacity of COVID-19 in children and pregnant women. In other words, the platform gathers different Pediatrics studies related to COVID-19 to improve the treatment, outcome, and transmission, for instance at school such as in this study, of the pediatric population.

Other Kids Corona Projects:SARS-CoV-2 seroconversion during the postoperative period in pediatric patients“, “Identifying SARS-CoV-2 in breast milk as a potential means of vertical transmission“, “Susceptibility to COVID-19 in pediatric age: Study of cases and household contacts“,“Susceptibility to COVID-19 in Pediatric Age: Study of Cases in School-like Environments” , “Characterization of COVID-19 in the Pediatric Population: Study of Sero-surveillance and of Immunological and Biochemical Biomarkers of Disease Severity” and “COVID-Preg: Efficacy and Safety of Hydroxychloroquine in Preventing SARS-CoV-2 Infection and Severe COVID-19 Illness During Pregnancy”

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