Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer
Philip C. Mack,
Chih-Yuan Hsu,
Ananda M. Rodilla,
Jorge E. Gomez,
Jazz Cagan,
Yuanhui Huang,
Sooyun Tavolacci,
Rajesh M. Valanparambil,
Nicholas Rohs,
Rachel Brody,
Brittney Nichols,
Juan Manuel Carreño,
Sheena Bhalla,
Christian Rolfo,
David E. Gerber,
Amy Moore,
Jennifer C. King,
Rafi Ahmed,
John D. Minna,
Paul A. Bunn,
Adolfo García-Sastre,
Florian Krammer,
Fred R. Hirsch,
Yu Shyr
Affiliations
Philip C. Mack
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Chih-Yuan Hsu
Department of Biostatistics, Vanderbilt University, Nashville, TN 37235, USA
Ananda M. Rodilla
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Jorge E. Gomez
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Jazz Cagan
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Yuanhui Huang
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Sooyun Tavolacci
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Rajesh M. Valanparambil
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Nicholas Rohs
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Rachel Brody
Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Brittney Nichols
GO2 Foundation for Lung Cancer, Washington, DC 20006, USA
Juan Manuel Carreño
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Sheena Bhalla
Hamon Center for Therapeutic Oncology Research, Departments of Internal Medicine and Pharmacology UT Southwestern Medical Center, Dallas, TX 75235, USA
Christian Rolfo
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
David E. Gerber
Hamon Center for Therapeutic Oncology Research, Departments of Internal Medicine and Pharmacology UT Southwestern Medical Center, Dallas, TX 75235, USA
Amy Moore
LUNGevity Foundation, Bethesda, MD 20814, USA
Jennifer C. King
GO2 Foundation for Lung Cancer, Washington, DC 20006, USA
Rafi Ahmed
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
John D. Minna
Hamon Center for Therapeutic Oncology Research, Departments of Internal Medicine and Pharmacology UT Southwestern Medical Center, Dallas, TX 75235, USA
Paul A. Bunn
Department of Internal Medicine, University of Colorado Cancer Center, Denver, CO 80045, USA
Adolfo García-Sastre
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Florian Krammer
Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Fred R. Hirsch
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Yu Shyr
Department of Biostatistics, Vanderbilt University, Nashville, TN 37235, USA
In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients—median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p p p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers.
