Covid19
Conditions
Brief summary
The study is designed as an open, non-randomized, phase IV cohort study in which the mRNA vaccine Comirnaty will be given in two doses. Analyses will be performed on blood and saliva, investigating humoral and cellular vaccine responses. Occurence of local or systemic reactogenicity will be evaluated, as well as adverse events. The study will include persons with primary or secondary immunosuppressive disorders, as well as immunocompetent persons, with the aim of investigating if the immune responses after given Comirnaty mRNA vaccine against COVID-19.
Detailed description
In this study with 450 patients with primary or secondary immunosuppressive disorders (patients with primary immunodeficiency, HIV infected patients, patients with allogenic stem cell transplantation/CAR T cell treated, solid organ transplanted, and patients with chronic lymphatic leukemia) from Karolinska University Hospital, and healthy controls of 90 individuals for comparison, we will investigate the safety and the immune responses after mRNA vaccination with Comirnaty after two doses, under 6 months of time for each participant. The study is In collaboration with research groups at Karolinska Institutet and SciLifeLab, with planned in-depth detailed analyses of antibody responses as well as cellular responses. The study has obtained permission from Swedish Medical Agency and Swedish Ethical Review Authority.
Interventions
BIOLOGICALComirnaty (COVID-19, mRNA vaccine)
Comirnaty will be administered two times, one at Day 0 and the second dose at Day 21.
Sponsors
Karolinska Institutet
Karolinska University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1\. Individuals ≥18 years old 2a. In the opinion of the investigator, individuals with immunosuppressive disease who meet one of the following criteria: * Primary immunodeficiency * Human immunodeficiency virus (HIV)-infection * Allogeneic stem cell transplantation / Chimeric antigen receptor (CAR T cell) therapy * Solid organ transplant * Chronic lymphatic leukemia or 2b. In the opinion of the investigator, individuals without immunosuppressive disease or treatment without significant co-morbidity 3\. Provision of signed informed consent to participate in the study
Exclusion criteria
1. Previous or ongoing Coronavirus Disease-19 (COVID-19). 2. Coagulation disorders, other conditions associated with prolonged bleeding time or anticoagulant treatments, which according to the investigator contraindicate intramuscular injection. Conditions which can be corrected with measures such as platelet concentrate treatments, coagulation factors or other measures for people responsible for anticoagulants are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals. | 2 weeks after second dose of vaccine. | Proportion (95% confidence interval, CI) seroconverting to positive response to SARS-CoV-2 IgG serology test after two doses of vaccine, measured 2 weeks after second dose of vaccine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Any Adverse Events (AE) of the Given Vaccine. | Duration of 0-14 days after the first vaccine dose. | Proportion (95% CI) who experience adverse events, with AE/SAE/SUSAR (after dose 1) |
| Frequency Who Experience Local and Systemic Reactions | After the first vaccin dose | Number and proportion (95% CI) who experience local and systemic reactions (after dose 1) |
| Frequency of SARS-CoV-2 Infection Documented by PCR Test. | 0 - 6 months | Proportion (95% CI) diagnosed with a new SARS-CoV-2 infection confirmed by a positive PCR test |
Countries
Sweden
Participant flow
Recruitment details
Recruitment of the primary study population (immunosuppressed participants ) took place at Karolinska University Hospital. The control group was recruited, for example, from among staff at Karolinska University Hospital and, if necessary, from other healthcare units or facilities, such as primary care centers, via the Always Open app, recruitment flyers, or advertisements.
Pre-assignment details
781 participants were screened for the study at at Karolinska University Hospital between February 12th and 22nd, 2021 and 539 were included and recived the first vaccin dose. The main reasons for screening failure were previous COVID-19 infection, patient refusal, and that some study subjects already had been vaccinated outside the study.
Participants by arm
| Arm | Count |
|---|---|
| All Immunocompromised Patients This arm consists of individuals with a primary immunodeficiency disorder. | 449 |
| Controls The control group consisted of individuals without a primary immunodeficiency disorder. | 90 |
| Total | 539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event, serious fatal | 3 | 0 |
| Overall Study | Died in original disease | 2 | 0 |
| Overall Study | Leukemia relapse (more than 6 weeks after dose 2) | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Controls | All Immunocompromised Patients |
|---|---|---|---|
| Absolute lymphocyte count(10^9 cells/L) at baseline | 1.6 Absolute lymphocyte count (10^9 cells/L) | 1.8 Absolute lymphocyte count (10^9 cells/L) | 1.6 Absolute lymphocyte count (10^9 cells/L) |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 331 Participants | 63 Participants | 268 Participants |
| Age, Categorical Between 18 and 65 years | 208 Participants | 27 Participants | 181 Participants |
| Immunogloublin G (IgG) level at baseline | 10.1 Immunglobulin G, IgG (g/L) | 11.0 Immunglobulin G, IgG (g/L) | 9.9 Immunglobulin G, IgG (g/L) |
| Ongoing immunosuppression at baseline Corticosteroids | 26 Participants | 0 Participants | 26 Participants |
| Ongoing immunosuppression at baseline No ongoing immunosuppression at baseline | 354 Participants | 90 Participants | 264 Participants |
| Ongoing immunosuppression at baseline Other immunosuppressive agents | 159 Participants | 0 Participants | 159 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment Sweden | 539 participants | 90 participants | 449 participants |
| Sex: Female, Male Female | 293 Participants | 51 Participants | 242 Participants |
| Sex: Female, Male Male | 246 Participants | 39 Participants | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 449 | 0 / 90 |
| other Total, other adverse events | 173 / 449 | 11 / 90 |
| serious Total, serious adverse events | 23 / 449 | 0 / 90 |
Outcome results
Primary
Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals.
Proportion (95% confidence interval, CI) seroconverting to positive response to SARS-CoV-2 IgG serology test after two doses of vaccine, measured 2 weeks after second dose of vaccine.
Time frame: 2 weeks after second dose of vaccine.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Immunocompromised Patients | Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals. | Seroconverted | 280 Participants |
| All Immunocompromised Patients | Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals. | Seronegative | 108 Participants |
| Controls | Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals. | Seroconverted | 78 Participants |
| Controls | Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals. | Seronegative | 0 Participants |
p-value: <0.05Fisher Exact
Secondary
Assessment of Any Adverse Events (AE) of the Given Vaccine.
Proportion (95% CI) who experience adverse events, with AE/SAE/SUSAR (after dose 1)
Time frame: Duration of 0-14 days after the first vaccine dose.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SUSAR | 1 Participants |
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SAE | 10 Participants |
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | No AE/SAE/SUSAR | 344 Participants |
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | AE | 94 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | No AE/SAE/SUSAR | 84 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SAE | 0 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SUSAR | 0 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | AE | 6 Participants |
Secondary
Assessment of Any Adverse Events (AE) of the Given Vaccine.
Proportion (95% CI) who experience adverse events, with AE/SAE/SUSAR (after dose 2)
Time frame: Duration of 0-14 days after the second vaccine dose.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | AE | 87 Participants |
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SAE | 13 Participants |
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SUSAR | 0 Participants |
| All Immunocompromised Patients | Assessment of Any Adverse Events (AE) of the Given Vaccine. | No AE/SAE/SUSAR | 346 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | No AE/SAE/SUSAR | 83 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | AE | 5 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SUSAR | 0 Participants |
| Controls | Assessment of Any Adverse Events (AE) of the Given Vaccine. | SAE | 0 Participants |
Secondary
Frequency of SARS-CoV-2 Infection Documented by PCR Test.
Proportion (95% CI) diagnosed with a new SARS-CoV-2 infection confirmed by a positive PCR test
Time frame: 0 - 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Immunocompromised Patients | Frequency of SARS-CoV-2 Infection Documented by PCR Test. | No | 370 Participants |
| All Immunocompromised Patients | Frequency of SARS-CoV-2 Infection Documented by PCR Test. | Yes | 18 Participants |
| Controls | Frequency of SARS-CoV-2 Infection Documented by PCR Test. | Yes | 2 Participants |
| Controls | Frequency of SARS-CoV-2 Infection Documented by PCR Test. | No | 76 Participants |
Secondary
Frequency Who Experience Local and Systemic Reactions
Number and proportion (95% CI) who experience local and systemic reactions (after dose 1)
Time frame: After the first vaccin dose
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Immunocompromised Patients | Frequency Who Experience Local and Systemic Reactions | Any reaction (grade 1 - 4) | 378 Participants |
| All Immunocompromised Patients | Frequency Who Experience Local and Systemic Reactions | No reaction | 66 Participants |
| Controls | Frequency Who Experience Local and Systemic Reactions | Any reaction (grade 1 - 4) | 71 Participants |
| Controls | Frequency Who Experience Local and Systemic Reactions | No reaction | 18 Participants |
p-value: <0.05Chi-squared
Secondary
Frequency Who Experience Local and Systemic Reactions
Number and proportion (95% CI) who experience local and systemic reactions (after dose 2)
Time frame: After the second vaccin dose
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Immunocompromised Patients | Frequency Who Experience Local and Systemic Reactions | Any reaction (grade 1 - 4) | 337 Participants |
| All Immunocompromised Patients | Frequency Who Experience Local and Systemic Reactions | No reaction | 85 Participants |
| Controls | Frequency Who Experience Local and Systemic Reactions | Any reaction (grade 1 - 4) | 74 Participants |
| Controls | Frequency Who Experience Local and Systemic Reactions | No reaction | 13 Participants |
p-value: <0.05Chi-squared