Prospective Natural History Study of Smoking, Immune Cell Profiles, Epigenetics and COVID-19
Condition: COVID-19
MeSH terms: COVID-19
Study type: Observational

Summary: 
      Background:

      Early evidence in the COVID-19 pandemic suggests that smokers are at a higher risk of having
      severe effects or dying from the disease. Smoking causes changes in immune cells. Researchers
      think this may be the reason why smokers are more likely to have severe effects from
      COVID-19. Researchers want to better understand the interaction between smoking history, the
      immune system, and COVID-19.

      Objective:

      To better understand how COVID-19 affects smokers and non-smokers immune systems before and
      after being infected with the virus.

      Eligibility:

      Healthy people ages 30-55 who are a smokers or non-smokers who may potentially contract
      COVID-19

      Design:

      Participants will be screened over the phone. They will answer questions about their
      demographics, medical history, medications, and smoking status.

      Participants will have up to 6 monthly visits.

      At the first visit, participants will have blood tests. Blood will be drawn through a needle
      in an arm vein. They will provide a saliva sample in a container and have a cheek swab. The
      participant will also have a nasal swab to see if they currently have COVID-19. Their height
      and weight will be taken. They will complete questionnaires about their medical history and
      smoking status.

      Participants will then have monthly visits. They will have blood draws to test for COVID-19
      antibodies. They will provide a saliva sample in a container and have a cheek swab. The
      participant will also have a nasal swab to see if they currently have COVID-19.

      These visits will occur 4 times or until they have a positive antibody result.

      Participants will have a final visit. They will have blood tests. They will provide a saliva
      sample in a container and have a cheek swab. The participant will also have a nasal swab to
      see if they currently have COVID-19.

      If at any time participants test positive for a COVID-19, they will be rescheduled 14 days or
      more after they no longer have symptoms....
    

Detailed description: 
      Study Description:

      This study is a prospective, longitudinal, observational, single-center, exploratory study to
      collect samples and data that will enable explorations of the interaction between smoking,
      immune system characteristics and Coronavirus Disease 2019 (COVID-19). This study will
      collect baseline samples and data prior to COVID-19 infection required to explore these
      interactions prospectively.

      Early evidence in the COVID-19 pandemic suggests that smokers have higher risk for morbidity
      and mortality associated with COVID-19 infection. We have identified smoking-associated
      altered epigenetics, transcription and changes in immune cell profiles.

      Smoking exposure drives loss of naive CD8+ T cells and increases in senescent CD8+ T cells
      and these effects are signs of immune system dysfunction. We propose that the immune system
      senescence associated with prior smoking is a susceptibility factor in COVID-19 morbidity.

      Objectives:

      Primary Objective:

      To prospectively collect biospecimens and data at baseline and longitudinally in an
      identified fashion from eligible participants and retain for future use to better understand
      the interaction between smoking history, immune cell profiles and the natural history of
      COVID-19 morbidity. We hypothesize that senescent CD8 T cells will be higher in smokers who
      develop COVID-19.

      To test this hypothesis, we will establish a bank of cryopreserved peripheral blood
      mononuclear cells (PBMCs) from before and after COVID-19 exposure from smokers and nonsmokers
      and use mass cytometry (CyTOF) to analyze detailed immune profiles, test if the frequency of
      senescent CD8 T cells is higher among smokers who develop COVID-19 (antibody positivity)
      relative to those who do not develop COVID-19 positivity.

      Exploratory Objective:

      To compare potential immunological biomarkers of susceptibility to viral infection with
      genetic, epigenetic and other biological characteristics measured in blood before, at one
      timepoint after recovery from COVID-19 illness and/or post-COVID-19 vaccination and develop
      assays that indicate immune cell dysfunction and COVID-19 susceptibility.

      Endpoints:

      Primary Endpoint:

      Levels of senescent CD16+CD8+ T cells before COVID-19 and time to COVID-19 morbidity.

      Exploratory Endpoints:

        1. Smoking exposure biomarkers

        2. Immune cell profiles identified by CyTOF assays or other single cell assays

        3. Transcriptional profiles from immune cell subtypes

        4. DNA methylation profiles of candidate genes in immune cell subtypes

      Study Population:

      Male and female participants aged 30 to 55 years old, generally healthy with a history of
      smoking (n=60) and nonsmoking (n=30).

      Description of Sites/Facilities Enrolling Participants:

      All visits will be conducted at the NIEHS Clinical Research Unit (CRU) in Durham, North
      Carolina, USA.

      Study Duration: Estimated time from enrollment to completion of data analyses is 24 months.

      Participant Duration:

      Estimated average amount of time for a participant to complete all study visits is 6 months.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy smokers and nonsmokers age 30-55 years
      
Keywords: Smoke Exposure; CyTOF Assay; Non-Smoker; Antibody Test; Natural History