Gut Microbiota Profile and Its Impact on Immunity Status in COVID-19 Vaccinated Cohorts

Study Overview
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Brief Summary
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This study aims to examine the association between gut microbiota composition and the magnitude and duration of immune response in subjects who have received different COVID-19 vaccines in Hong Kong and to identify the differences compared to those COVID-19 recovered subjects.

Detailed Description
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SARS-CoV-2, the cause of COVID-19, emerged as a new zoonotic pathogen of humans at the end of 2019 and rapidly developed into a global pandemic in March 2020. Over 106 million COVID-19 cases including 2.3 million deaths have been reported to the WHO as of February 9th 2021. Overall 80% of cases are mild/moderate or asymptomatic while 20% may develop severe or critical disease with respiratory failure requiring oxygen support and intensive care. As of 16 February 2021, 10789 cases have been confirmed in HK with 193 deaths while 10231 patients have been discharged from acute public hospitals with a mean length of stay of 15 days. Up to 16 Feb., 2021, there were 568 patients with COVID-19 have been managed at the Prince of Wales Hospital (PWH) with 12 deaths. Studies showed that the quality of life of the patients who have recovered from COVID-19 was impaired. This situation is similar to some patients who suffered from SARS-CoV1 infection in 2003. Natural infection by virus triggers an effective system immunity so that the host can resist or highly reduce the chance of re-infection. In many cases, this protection can maintain a long period of time. On the other hand, vaccination, which aims to induce the similar immunity but in a controlled manner, presents only selected antigen(s) to the host through different delivery strategies. Lacking a normal virus replication cycle, vaccination can only partially mimic the infection process that makes the immunogenicity or durability of the vaccines sometimes not as effective as natural infection. This situation was also observed during the development of SARS and MERS vaccines. A number of studies focused on examining the humoral and cellular immunities from the COVID-19 patients during their acute stage or only few months after recovery. However, the long-term immunities (over a year) from the patients are not yet very clear. The HKSAR government has procured 2 different types of COVID-19 vaccines for all the HK citizens that is one of the few regions/countries adopt this strategy. BioNTech mRNA vaccination programme will commence in early March 2021 and Sinovac inactivated whole virus vaccine will also be available soon for vaccination after formal approval recently. All these vaccines are so far only evaluated at their own designated population and countries and there is still lack of prospective study to side-by-side comparing the microbial biomarkers in the stool of different vaccines. Having different vaccines which will soon be available in Hong Kong, it would be of great interest to investigate and compare the microbial biomarkers in the stool of recovered COVID-19 patients versus those who have received different COVID-19 vaccines by setting up a 2-year longitudinal study.

Official Title
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Longitudinal Assessment of Gut Microbiota Profile and Its Impact on Immunity Status in COVID-19 Vaccinated Cohorts in Hong Kong

Conditions
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COVID-19 Vaccination, Gut Microbiota

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Vaccination (VAC) cohort: aged ≥ 18 years old; and have documented to have no previous COVID-19 infection; and will receive any type of COVID-19 vaccines; and agree to hand in study samples (stool and blood); and agree to sign the informed consent Inclusion Criteria for COVID-19 convalescent (CON) cohort: aged ≥ 18 years old; and recovered from varying severity of COVID-19; and agree to hand in study samples (stool and blood); and agree to sign the informed consent Exclusion Criteria: None

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VAC cohort<br>Subjects who will take COVID-19 vaccines | |
| CON cohort<br>Subjects who are COVID-19 survivors | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify and compare the microbiome profile and immune response | To identify and compare the microbiome profile and immune response in subjects who have received different COVID-19 vaccines and in subjects who recovered from COVID-19 in Hong Kong | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 IgG antibody level | SARS-CoV-2 IgG antibody level in VAC cohort | across 24 months | 
| Compare the serum neutralization assay against pseudovirus and live virus, as well as the detection of IgM and IgG against receptor-binding domain [RBD] and S1 | Compare the serum neutralization assay against pseudovirus and live virus, as well as the detection of IgM and IgG against receptor-binding domain [RBD] and S1 | across 24 months | 
| SARS-CoV-2 specific antibody | Compare the levels of SARS-CoV-2 specific antibody | across 24 months |