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.

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 and after recovery from COVID-19 illness and develop assays that indicate immune cell dysfunction and COVID-19 susceptibility.

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.