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

• ClinicalTrials.gov Identifier: NCT04912700
• Recruitment Status: Completed
• First Posted: June 3, 2021
• Results First Posted: September 30, 2021
• Last Update Posted: September 30, 2021
• Sponsor: William Beaumont Hospitals
• Information provided by (Responsible Party): Amit Bahl, William Beaumont Hospitals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Covid19	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 Design

• Study Type: Observational
• Actual Enrollment: 11834 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: The Impact of Vaccination on Severity of Illness in COVID-19: A Multicenter Cohort Study
• Actual Study Start Date: June 1, 2021
• Actual Primary Completion Date: June 7, 2021
• Actual Study Completion Date: June 7, 2021

Groups and Cohorts

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 Name: 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 Name: Pfizer vaccine, Moderna vaccine, Johnson & Johnson vaccine

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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.

Contacts and Locations

Locations

United States, Michigan

Beaumont Hospital - Royal Oak

Royal Oak, Michigan, United States, 48073

Sponsors and Collaborators

William Beaumont Hospitals

Investigators

• Principal Investigator: Amit Bahl; William Beaumont Hospitals

  Study Documents (Full-Text)

Documents provided by Amit Bahl, William Beaumont Hospitals:

Study Protocol  [PDF] May 13, 2021

Statistical Analysis Plan  [PDF] May 13, 2021

More Information

Publications:

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

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.

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.

• Responsible Party: Amit Bahl, Director, Emergency Ultrasound, William Beaumont Hospitals
• ClinicalTrials.gov Identifier: NCT04912700
• Other Study ID Numbers: 2021-118
• First Posted: June 3, 2021
• Results First Posted: September 30, 2021
• Last Update Posted: September 30, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plan at this point.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amit Bahl, William Beaumont Hospitals:

vaccination; efficacy; severe outcomes; mortality; variants; breakthrough infection; COVID-19; SARS-Cov-2 virus

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs