COVID-19 Vaccination of Immunodeficient Persons (COVAXID)

Study Overview
=================
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.

Official Title
-----------------
Immunological Responses After Vaccination for COVID-19 With the Messenger Ribonucleic Acid (mRNA) Vaccine Comirnaty in Immunosuppressed and Immunocompetent Individuals. An Open and Non-randomized, Phase IV Multicenter Study

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: Comirnaty (COVID-19, mRNA vaccine)


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Previous or ongoing Coronavirus Disease-19 (COVID-19). 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 exclusion criteria. Planned to receive another vaccine within 14 days before the first dose of the study vaccine, or during the period from the first dose of the study vaccine up to 14 days after the second dose of the study vaccine, and vaccination with another vaccine which in the investigator's opinion cannot be planned outside these time periods Pregnancy or breast feeding. Hypersensitivity to the active substance or to any of the excipients contained in the vaccine Individuals who cannot understand the informed consent. Individuals who for other reasons are considered by investigators as not suitable for inclusion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccination with Comirnaty according to standard of care treatment<br>All study participants will receive Comirnaty according to current approval. | Biological: Comirnaty (COVID-19, mRNA vaccine)<br>* Comirnaty will be administered two times, one at Day 0 and the second dose at Day 21.<br>* Other names: Pfizer mRNA vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 weeks after second dose of vaccine. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of any Adverse Events (AE) of the given vaccine [Safety and tolerability]. | Proportion (95% CI) of study objects experiencing AE including reactogenicity, Serious Adverse Events (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR). | Duration of 0-14 days after each given vaccine dose. | 
| Frequency of SARS-CoV-2 infection documented by positive polymerase chain reaction (PCR) test. | Proportion (95% CI) of study objects with SARS-CoV-2 infection. | Day 0 - 6 months. | 
| Assessment of humoral and cellular immune responses in blood and saliva. | Description of humoral and cellular immune responses in blood and saliva at baseline, and at time points day 0 (first vaccine dose), day 10 after first dose, day 21 (second vaccine dose), and 2 weeks, 3 months and 6 months after the second vaccine dose. | Day 0- 6 months. | 
| Assessment of escape mutations of sequencing SARS-CoV-2 at breakthrough infection. | Genomic sequencing of SARS-CoV-2 at breakthrough infection. | Day 0-6 months. | 
| Assessment of graft versus host disease in allogenic stem cell transplanted persons after given vaccine. | Number of occurrence or worsening of graft versus host disease in allogenic stem cell transplanted persons after given vaccine will be described. | Day 0-6 months. | 
| Assessment of biopsy verified rejection in solid organ transplanted persons after given vaccine. | Number of occurrence of biopsy verified rejection in solid organ transplanted persons after given vaccine. | Day 0-6 months. | 
| Assessment of viremia, defined as HIV ribonucleic acid (RNA) > 50 copies/milliliter after vaccination in HIV infected persons. | Number of HIV infected persons with HIV ribonucleic acid (RNA) > 50 copies/milliliter after vaccination. | Day 0-6 months. | 
| Assessment of HIV deoxyribonucleic acid (DNA) levels after given vaccine in HIV infected persons. | HIV DNA levels at baseline, and 3 and 6 months after second dose of vaccine. | Day 0-6 months. | 
| Assessment of oral and gut microbiota in immunosuppressed and controls, in relation to immune response to vaccination. | Description of oral and fecal microbiota at baseline and association to immune responses. | Day 0-6 months. |