The Impact of Vaccination on Severity of Illness in COVID-19

Study Overview
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Brief Summary
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With the FDA's emergency use authorization declaration in December of 2020, the Pfizer-BioNtech vaccine became the first of several vaccines to kick off the mass vaccination effort across the United States against CoronaVIrus Disease 2019 (COVID-19). Subsequently, Moderna as well as Johnson and Johnson both had vaccines receive emergency use authorization. While the Pfizer and the Moderna vaccines both utilize novel mRNA technology, Johnson and Johnson's vaccine uses a viral vector that has been used previously in both the approved European Ebola vaccine and a trial vaccine for HIV. However, none of these vaccine types have previously been approved in the United States. While preliminary data from safety and efficacy trials have shown positive results, actual-world data on its effectiveness is still lacking. Several small cohort studies and one large trial from Israel are currently the only insights into the actual rates of infection, hospitalization, and severe illness among vaccinated individuals. As COVID-19 variants, with the potential to reduce vaccine efficacy, continue to emerge worldwide, there is a need of more data regarding the real-world effectiveness of our current mass vaccination efforts. Vaccination efforts in the State of Michigan have been ongoing since December 2020. Given that approximately 33.7% of the state's population is either partially or fully vaccinated, it is unclear why the number of cases has risen so dramatically or if immunization efforts can help the situation. Given the current situation in the State of Michigan, this study will evaluate the efficacy of COVID-19 vaccination on rates of hospital visits and severe illness when breakthrough Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) infection occurs in a region with high incidence of variant strain disease.

Detailed Description
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A retrospective chart review of all patients presenting to Beaumont Health System emergency departments between December 15, 2020 and April 30, 2021 who tested positive for COVID-19 will be performed. The primary aim is to compare the rate of Emergency Department (ED) presentations/hospitalizations among unvaccinated, partially vaccinated, and fully vaccinated patients presenting to an emergency center (EC). Secondarily, the rates of individual clinical outcomes of COVID-19 infection for hospitalized patients will be compared among unvaccinated, partially vaccinated, and fully vaccinated patients, including the proportion of COVID-positive patients who develop severe disease, require admission to the hospital, and rates of those requiring intensive care unit (ICU) admission, mechanical ventilation, extracorporeal membrane oxygenation (ECMO), renal replacement therapy (RRT), supplemental oxygenation, or noninvasive ventilation, as well as the rate of in-hospital mortality and the hospital length of stay. Exploratory outcomes may include comparisons among fully-vaccinated individuals receiving each of the three types of vaccines, and investigation of demographic, epidemiological, clinical and laboratory predictors of hospitalization. For each individual, data collected will include vital signs (temperature, blood pressure, heart rate, respiratory rate, pulse oximetry), demographics (age, gender, existing medical conditions), home medications, chief complaint from emergency provider note, duration of symptoms in days at the time of presentation from emergency provider note, chest X-ray or chest computed tomography (CT) results, and laboratory values. For patients who were admitted, data collected will include initial hospital admission unit (regular medical or surgical floor, progressive floor, intensive care unit), change in unit type during admission, oxygen therapy (none, nasal cannula, supplemental high flow oxygen, ventilator), days on high flow oxygen, days on ventilator, specific inpatient medical therapies, laboratory values, imaging results, hospital length of stay, and disposition from hospital (home, rehabilitation unit, death).

Official Title
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The Impact of Vaccination on Severity of Illness in COVID-19: A Multicenter Cohort Study

Conditions
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Covid19

Intervention / Treatment
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* Biological: COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients presenting to Beaumont Health emergency departments who have tested positive for COVID-19 between December 15, 2020 and April 30, 2021 with available vaccination data through state of Michigan registry. Exclusion Criteria: Patients who have previously tested positive for COVID-19 prior to the study period will be excluded. Patients with missing vaccine status will be excluded.

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Unvaccinated<br>Unvaccinated individuals are defined as having positive laboratory COVID-19 testing with no record of immunization against COVID-19 or first-dose vaccination after symptom onset. | |
| Partially vaccinated<br>Partially vaccinated individuals are defined as having positive laboratory COVID-19 testing and symptom onset after a single dose of either mRNA (Pfizer, Moderna) vaccine, or < 14 days after the second dose of either mRNA vaccine (Pfizer, Moderna) or < 14 days after the administration of the single dose of viral vector vaccine (Johnson & Johnson). | Biological: COVID-19 vaccine<br>* Full or partial reception of vaccine<br>* Other names: Pfizer vaccine, Moderna vaccine, Johnson & Johnson vaccine;|
| Fully vaccinated<br>Fully vaccinated individuals are defined as having positive laboratory testing for COVID-19 and symptom onset >14 days since administration of second dose of either mRNA vaccine, or >14 days since administration of viral vector vaccine (Johnson & Johnson). | Biological: COVID-19 vaccine<br>* Full or partial reception of vaccine<br>* Other names: Pfizer vaccine, Moderna vaccine, Johnson & Johnson vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Emergency Center (EC) Encounters and/or Hospitalizations With Positive COVID-19 Test | Number of participants with encounters at emergency center (EC) and /or hospitalizations with positive COVID-19 test | During the period from December 15, 2020 through April 30, 2021 (up to 5 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Severe Infection | Patient with any of the following: ICU admission, mechanical ventilation, or in-hospital mortality | During EC visit or hospitalization, from date of presentation until May 15, 2021 (up to 5 months) | 
| Number of Patients With ICU Admission | Number of patients admitted to ICU during hospital stay | During hospitalization, from date of admission until May 15, 2021 (up to 5 months) | 
| Number of Patients Requiring Mechanical Ventilation | Number of patients who required mechanical ventilation | During EC visit or in-patient hospitalization, from date of presentation until May 15, 2021 (up to 5 months) | 
| Number of Patients With In-hospital Mortality | Number of patients who died during EC visit or hospital admission | During EC visit or in-patient hospitalization, from date of presentation until May 15, 2021 (up to 5 months) | 
| Number of Hospitalized Patients Requiring Extracorporeal Membrane Oxygenation (ECMO) | Number of hospitalized patients requiring ECMO | During hospitalization, from date of admission until May 15, 2021 (up to 5 months) | 
| Number of Hospitalized Patients Requiring Renal Replacement Therapy (RRT) | Number of hospitalized patients requiring RRT | During hospitalization, from date of presentation until May 15, 2021 (up to 5 months) | 
| Number of Hospitalized Patients Requiring Supplemental Oxygen | Number of hospitalized patients requiring supplemental oxygen, by type | During hospitalization, from date of admission until May 15, 2021 (up to 5 months) | 
| Number of Hospitalized Patients Requiring Non-invasive Ventilation | Number of hospitalized patients requiring non-invasive ventilation | During EC visit or hospitalization, from date of presentation until May 15, 2021 (up to 5 months) | 
| Number of Hospitalized Patients Requiring Vasopressors | Number of hospitalized patients with hypotension requiring vasopressors | During EC visit or hospitalization, from date of presentation until May 15, 2021 (up to 5 months) | 
| Number of Patients Discharged From Hospital to Home, Skilled Nursing Facility, Rehabilitation Facility, or Hospice. | Number of patients discharged from in-patient hospital admission to home, skilled nursing facility, rehabilitation facility, or hospice. | During the period from December 15, 2020 through May 15, 2021 (up to 5 months) | 
| Hospital Length of Stay | Number of days from admission after emergency center (EC) visit and positive COVID-19 test, until discharge | During the period from December 15, 2020 through May 15, 2021 (up to 5 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccination, efficacy, severe outcomes, mortality, variants, breakthrough infection, COVID-19, SARS-Cov-2 virus