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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Biological: COVID-19 vaccine

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 11834

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital - Royal Oak

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients during study period with COVID-19 infection and EC visit.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Unvaccinated; 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; 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; Full or partial reception of vaccine; Other Names: Pfizer vaccine, Moderna vaccine, Johnson & Johnson vaccine
Fully vaccinated; 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; Full or partial reception of vaccine; Other Names: Pfizer vaccine, Moderna vaccine, Johnson & Johnson vaccine

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: William Beaumont Hospitals
• Investigators: Principal Investigator: Amit Bahl, William Beaumont Hospitals

Publications and helpful links

General Publications

• Lurie N, Saville M, Hatchett R, Halton J. Developing Covid-19 Vaccines at Pandemic Speed. N Engl J Med. 2020 May 21;382(21):1969-1973. doi: 10.1056/NEJMp2005630. Epub 2020 Mar 30. No abstract available.
• Azar AM. Emergency Use Authorization Declaration. Published online 2020. https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration
• US Food and Drug Administration. FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine. Accessed April 10, 2021. https://www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-third-covid-19-vaccine
• Emary KRW, Golubchik T, Aley PK, Ariani CV, Angus B, Bibi S, Blane B, Bonsall D, Cicconi P, Charlton S, Clutterbuck EA, Collins AM, Cox T, Darton TC, Dold C, Douglas AD, Duncan CJA, Ewer KJ, Flaxman AL, Faust SN, Ferreira DM, Feng S, Finn A, Folegatti PM, Fuskova M, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hallis B, Heath PT, Hay J, Hill HC, Jenkin D, Kerridge S, Lazarus R, Libri V, Lillie PJ, Ludden C, Marchevsky NG, Minassian AM, McGregor AC, Mujadidi YF, Phillips DJ, Plested E, Pollock KM, Robinson H, Smith A, Song R, Snape MD, Sutherland RK, Thomson EC, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Williams CJ, Hill AVS, Lambe T, Gilbert SC, Voysey M, Ramasamy MN, Pollard AJ; COVID-19 Genomics UK consortium; AMPHEUS Project; Oxford COVID-19 Vaccine Trial Group. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial. Lancet. 2021 Apr 10;397(10282):1351-1362. doi: 10.1016/S0140-6736(21)00628-0. Epub 2021 Mar 30.
• Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernan MA, Lipsitch M, Reis B, Balicer RD. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021 Apr 15;384(15):1412-1423. doi: 10.1056/NEJMoa2101765. Epub 2021 Feb 24.
• Daniel W, Nivet M, Warner J, Podolsky DK. Early Evidence of the Effect of SARS-CoV-2 Vaccine at One Medical Center. N Engl J Med. 2021 May 20;384(20):1962-1963. doi: 10.1056/NEJMc2102153. Epub 2021 Mar 23. No abstract available.
• Amit S, Regev-Yochay G, Afek A, Kreiss Y, Leshem E. Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients. Lancet. 2021 Mar 6;397(10277):875-877. doi: 10.1016/S0140-6736(21)00448-7. Epub 2021 Feb 18. No abstract available.
• Sanders RW, de Jong MD. Pandemic moves and countermoves: vaccines and viral variants. Lancet. 2021 Apr 10;397(10282):1326-1327. doi: 10.1016/S0140-6736(21)00730-3. Epub 2021 Mar 30. No abstract available.
• State of Michigan COVID-19 Vaccine Dashboard. https://www.michigan.gov/coronavirus/0,9753,7-406-98178_103214-547150--,00.html. Retrieved 25 April 2021.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): June 7, 2021
• Study Completion (Actual): June 7, 2021

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 1, 2021
• First Posted (Actual): June 3, 2021

Study Record Updates

• Last Update Posted (Actual): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; efficacy; mortality; vaccination; severe outcomes; variants; breakthrough infection; SARS-Cov-2 virus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 2021-118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan at this point.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No