A new study in patients with the COVID-19 virus examined immune responses in those with hematologic malignancies, and the results highlighted the importance of CD8 T cells in circumstances of B-cell depletion. Study findings were reported in a preprint article posted to Research Square.

“A notable feature of the COVID-19 pandemic has been the dramatic heterogeneity in clinical presentations and outcomes, yet mechanistic explanations for the wide variance in disease severity have remained elusive,” the study investigators wrote in their report.

This prospective study evaluated demographics, clinical characteristics, and outcomes in 100 patients with cancer who were hospitalized with COVID-19 at any of 4 centers within the University of Pennsylvania Health System. In addition to this main cohort, the researchers examined patients with COVID-19 from 2 other cohorts, 1 containing 84 patients with cancer and the other containing 130 patients with or without cancer. The researchers performed flow cytometric and serological analyses of samples from patients across cohorts, in addition to donor controls without hematologic malignancies, to identify clusters of immune phenotypes.


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In the main study cohort, patients with hematologic malignancies showed a higher level of mortality within 30 days of discharge than patients with solid tumors did, even when accounting for performance status and status of cancer (adjusted odds ratio, 3.3 [95% CI, 1.01-10.8]; P =.048).

The researchers identified 5 immune phenotypes. A phenotype marked by depletion of CD8 T cells showed the greatest mortality and disease severity across all patients with cancer, despite having preserved B cells. In patients with hematologic malignancies who had depleted B cells, increased CD8 T cells were associated with reduced mortality.

Reportedly, immune phenotypes were similar between patients with solid tumors and patients without cancer. However, patients with hematologic cancers more often demonstrated impairments involving B cells, CD4 T cells, and antibody responses, but with CD8 T-cell activity that the researchers suggested may somewhat compensate for these impairments.

Anti-CD20-directed treatment was associated with impairment of B cells and SARS-CoV-2-related antibodies. However, in patients with sufficient CD8 T-cell function, mortality was not increased by this therapy.

“Taken together, these findings suggest that CD8 T cells are critical for anti-viral immunity in hematologic malignancy patients and may at least partially mitigate the negative impact of B-cell depletion on COVID outcomes,” the study investigators wrote. They also indicated that vaccination may help support T-cell response in patients with hematologic malignancies.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Bange EM, Han NA, Wileyto P, et al. CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer. Res Sq. Preprint posted online February 2, 2021. doi: 10.21203/rs.3.rs-162289/v1