COVID-19 onset and severity in children and adults: role of the nasopharyngeal microbiota and the host ACE2 receptor

Principal Investigators

Objectives

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. The project has four specific objectives:

  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.

Project design

Two approaches are considered according to the specific objectives:

Objective 1: Single-center retrospective case-control study with children. Cases and controls frequency-matched by age, sex, and time of sampling.

Objectives 2-4: Multi-center prospective case-control study with children and adults, including follow-up of cases (Objectives #3-4). Cases and controls matched by age, sex, and time of sampling*.

*Test negative design: subjects will be considered cases if PCR-positive for SARS-CoV-2 and controls if negative. Sub-analysis of cases admitted to ICU (severe COVID-19), hospitalized (moderate COVID-19), and outpatients and hospital staff (mild COVID-19).

Cohorts

Objective 1:

Cases: children aged ≤ 18 years old attended in HSJD and PCR-positive for HCoV.

Controls: children aged ≤ 18 years attended in in HSJD and PCR-negative for HCoV.

Objectives 2-4:

Cases: 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).

Controls: 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.

Samples

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).

Objectives 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.

Group members

External collaborators

Hospital Universitari Mútua de Terrassa (HUMT):

  • PI: Esther Calbo
  • LR: Yolanda Cuesta Mieza
  • Other researchers: Beatriz Dietl, Lucía Boix-Palop, Laura Marina Gisbert, Ana Blanco

Fundació per al Foment de la Investigació Biomèdica de la Comunitat València (FISABIO):

  • PI: Alex Mira
  • LR: José Antonio Manrique Martorell
  • Other researchers: Miguel Carda

Universitat Internacional de Catalunya (UIC):

  • PI: Josep Clotet
  • LR: Belen Castro