Prospective Monitoring of BNT162b2 Second Vaccination Booster Effects in Health Care Workers (HCW)

Study Overview
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Brief Summary
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The SARS-CoV-2 virus causes severe respiratory illness and is an ongoing global pandemic. On December 12, 2020 the FDA approved Pfizer's BioNTech vaccine BNT162b2 which is a messenger RNA type of vaccine for use. This vaccine has shown in numerous studies the ability to induce a strong immune response and provide both humeral and cellular protection against wild type, alpha and delta variants of SARS-CoV2 virus. In Israel the national vaccine operation began in mid-December 2020 which included 2 initial doses three weeks apart. In August 2021 a first booster (3rd dose) was provided to enhance protection and due to reports of reduced immune response and clinical protection. Several studies have demonstrated that over time there is a decay in the antibody levels, and with them reduced protection. Recently a new variant of concern has been identified (Omicron) and is causing a surge of infections worldwide. There is lack of knowledge regarding the effectiveness of the current schedule of vaccine against this new variant and whether a second booster (4th dose) will provide higher levels of clinical protection against this variant, currently the ministry of health is considering recommendations for a fourth dose for HCW. The purpose of this study is to examine whether a fourth dose of vaccination will provide better protection against infection and clinical disease.

Official Title
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Prospective Monitoring of BNT162b2 Second Vaccination Booster for Prevention of the COVID-19 Infection in Health Care Workers (HCW)

Conditions
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Coronavirus Infections

Intervention / Treatment
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* Biological: Pfizer BNT162b2 Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent. Healthcare worker in one of the Clalit Health Services Medical centers and is at least 18 years of age. Completed three doses of BNT162b2 according to MOH guidelines. Third dose was given at least 4 months prior to enrollment. Exclusion Criteria: History of COVID-19 infection. History of being treated or is currently being treated for any type of Malignancies or other co-morbid conditions that may result in protocol non-compliance. Currently or in the past three months was treated with any type of Immune suppression medication (including chemotherapy, immunomodulatory drugs, biological agents that affect the immune system, any immunosuppressive drug such as corticosteroids). Received in the past 4 months monoclonal antibodies of any type.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 |
| --- | --- |
| Three doses of vaccination<br>Subjects received three pfizer BNT162b2 vaccination at least four month before recruitment | |
| Four doses of vaccination<br>Subjects received three pfizer BNT162b2 vaccination at least four month before recruitment and decided to receive another dose at time of recruitment or followup | Biological: Pfizer BNT162b2 Vaccine<br>* The Pfizer-BioNTech COVID-19 vaccine (INN: tozinameran), sold under the brand name Comirnaty, is an mRNA-based COVID-19 vaccine developed by the German biotechnology company BioNTech. For its development, BioNTech collaborated with American company Pfizer to carry out clinical trials, logistics, and manufacturing. It is authorized for use in people aged five years and older in some jurisdictions, twelve years and older in some jurisdictions, and for people sixteen years and older in other jurisdictions, to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus. The vaccine is given by intramuscular injection. It is composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. Initial advice indicated that vaccination required two doses given 21 days apart, but the interval was later extended to up to 42 days in the US, and up to four months in Canada<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of positive PCR test for SARS-COV2 | Percent Positive PCR test | 30 days | 
| Proportion of positive PCR test for SARS-COV2 | Percent Positive PCR test | 60 days | 
| Proportion of positive PCR test for SARS-COV2 | Percent Positive PCR test | 90 days | 
| Proportion of positive PCR test for SARS-COV2 | Percent Positive PCR test | 120 days | 
| Proportion of positive PCR test for SARS-COV2 | Percent Positive PCR test | 150 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of symptomatic COVID 19 infection | Percent Positive PCR test | 30 days | 
| Proportion of symptomatic COVID 19 infection | Percent Positive PCR test | 90 days | 
| Proportion of symptomatic COVID 19 infection | Percent Positive PCR test | 182 days | 
| Proportion of COVID 19 infection requiring hospitalization | Percent Positive PCR test | 30days | 
| Proportion of COVID 19 infection requiring hospitalization | Percent Positive PCR test | 90 days | 
| Proportion of COVID 19 infection requiring hospitalization | Percent Positive PCR test | 182 days | 
| Levels of binding and neutralizing activity and avidity of the antibodies | binding antibody units per mL | 30 days | 
| Levels of binding and neutralizing activity and avidity of the antibodies | 50 Percent neutralization titer | 60 days | 
| Levels of binding and neutralizing activity and avidity of the antibodies | 50 Percent neutralization titer | 90 days | 
| Levels of binding and neutralizing activity and avidity of the antibodies | 50 Percent neutralization titer | 120 days | 
| Levels of binding and neutralizing activity and avidity of the antibodies | 50 Percent neutralization titer | 150 days | 
| Levels of binding and neutralizing activity and avidity of the antibodies | 50 Percent neutralization titer | 180 days | 
| Composite endpoint of serious adverse events | Percent Positive Anaphylaxis, Myocarditis | 14 days following the booster vaccination |