Vaccines (Jun 2024)

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

DOI
https://doi.org/10.3390/vaccines12070713
Journal volume & issue
Vol. 12, no. 7
p. 713

Abstract

Read online

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.

Keywords