Vaccine-elicited B and T cell immunity to SARS-CoV-2 is impaired in chronic lung disease patients (preprint)

The protection afforded by vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to individuals with chronic lung disease is not well established. To understand how chronic lung disease impacts SARS-CoV-2 vaccine-elicited immunity we performed deep immunophenotyping of the humoral and cell mediated SARS-CoV-2 vaccine response in an investigative cohort of vaccinated patients with diverse pulmonary conditions including asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD). Compared to healthy controls, 48% of vaccinated patients with chronic lung diseases had reduced antibody titers to the SARS-CoV-2 vaccine antigen as early as 3-4 months after vaccination, correlating with decreased vaccine-specific memory B cells. Vaccine-specific CD4 and CD8 T cells were also significantly reduced in patients with asthma, COPD, and a subset of ILD patients compared to healthy controls. These findings reveal the complex nature of vaccine-elicited immunity in high-risk patients with chronic lung disease.

Impaired SARS-CoV-2 mRNA vaccine antibody response in chronic medical conditions: a real-world data analysis (preprint)

This study is to investigate whether certain medical conditions may impair antibody response to the mRNA vaccines. In this unique study, participants were drawn from patients in National Jewish Health, a pulmonary specialty outpatient clinic.Our study highlights fact that 26% of our patients (n=226) who had spike protein ab measured at least 14 days post 2nd vaccine had negative spike protein ab testing. We found interstitial lung disease (ILD) to be an independent risk factor for impaired antibody response. While the exact antibody level that confers protection against SARS-CoV-2 is unknown and there may be other non-B cell-mediated protection (e.g. T cell-mediated), our study raises concerns that SARS-CoV-2 vaccination may not result in protective immunity in all populations and may have implications for some as masking and distancing strategies are abandoned.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design (preprint)

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.