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:
- 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.
- 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.
- 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.
- 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.
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).
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.
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.
- Nasopharyngeal aspirates representative of severe low respiratory infection (n = 150), mild upper respiratory infection (n = 150), and asymptomatic carriage and healthy status (n = 55).
- 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.
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