I thank Dr Korde and colleagues (1) for their valuable study to investigate whether the SARS-CoV-2 vaccination was associated with a lower incidence of COVID-19 severity in a longitudinal study in which adult cancer patients infected with COVID-19 were enrolled. In their study, they found a statistically significant association with a lower incidence of severe COVID-19 disease in fully vaccinated patients with cancer after infection with COVID-19 compared with those unvaccinated or partially vaccinated cancer patients. I agree with this study’s conclusion because the vaccines that prevent SARS-CoV-2 infection are generally recommended as the most promising method to restrain the pandemic (2), but there were several limitations to this study. Therefore it is essential that the results of the authors’ analysis should be interpreted with caution.
First, Supplementary Table 1 of this study (1) showed that the proportion of patients with chimeric antigen receptor (CAR) T-cell therapy at any time prior to a positive test in the group not fully vaccinated was larger than in the fully vaccinated group, while the group fully vaccinated of prior CAR-T cell therapy did not exhibit a reverse association of full vaccination with severe COVID-19, neither did the group not fully vaccinated. Meanwhile the CAR T-cell therapy, which is an important cancer treatment–related toxicity, can induce cytokine release syndrome (CRS) (3,4), which is an acute systemic inflammatory syndrome resulting from rapid immune activation and characterized by fever and multiple organ dysfunction that can progress to life threatening (4). Therefore, it is likely that the prior CAR T-cell–associated CRS is a potentially confounding factor for two groups, and it is not clear whether the prior CAR-T cell-associated CRS resulted in the impairments of cellular immune systems in bodies, so that it could more easily lead to severe COVID-19 for the group not fully vaccinated and could critically weaken the protective efficacy in reducing the incidence of severe COVID-19 from full vaccination for the fully vaccinated group.
Second, in Supplementary Table 1 of this study (1), the proportion of patients with COVID-19 treatment of monoclonal antibodies within 30 days of a positive test in the fully vaccinated group was greater than in the group not fully vaccinated, whereas the monoclonal antibody combination of tixagevimab-cilgavimab used in this study was previously considered an effective prevention before the exposure to COVID-19 in certain individuals expected to gain suboptimal protection from vaccination or who were unable to be vaccinated (5). Hence the greater proportion of treatment of monoclonal antibodies in the fully vaccinated group might be another potentially confounding factor.
Third, there were no data of COVID-19 treatment of glucocorticoids in the database of patient characteristics between the 2 groups. However, the data from previously randomized trials had largely confirmed the effect of glucocorticoids in treating severe COVID-19 (6); meanwhile, the glucocorticoids played an important role in the treatment of CAR T-cell–associated CRS (4), so whether the glucocorticoids in treating severe COVID-19 could have increased the potential confounding of this study should be a focus of future research.
Finally, it was unclear whether the levels of laboratory evidence of COVID-19, such as the elevated inflammatory markers (eg, D-dimer, ferritin, C-reactive protein, procalcitonin) and elevated proinflammatory cytokines (eg, interleukin-2, interleukin-6, tumor necrosis factor-α) (7), associated with critical and fatal illnesses, resulting from the severe diseases or deaths of the acute COVID-19 infection (7) rather than the malignancy-related severe diseases or deaths, between the 2 groups were comparable.
Supplementary Material
Acknowledgements
I would like to acknowledge the participating patients and enrolling sites, as well as the members of the NCCAPS Working Group regarding the study I comment.
Data availability
Data is openly available in a public repository that issues datasets with DOIs.
Author contributions
Shan Song, BM (conceptualization; investigation; writing—review and editing; writing—original draft).
Funding
No funding was used for this manuscript.
Conflicts of interest
None reported.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data is openly available in a public repository that issues datasets with DOIs.