CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer

Bange, Erin; Han, Nicholas; Wileyto, Paul; Kim, Justin; Gouma, Sigrid; Robinson, James P.; Greenplate, Allison R.; Hwee, Madeline A.; Porterfield, Florence; Owoyemi, Olutosin; Naik, Karan; Zheng, Cathy; Galantino, Michael; Weisman, A.R.; Ittner, C.A.G.; Kugler, Emily M.; Baxter, Amy E.; Oniyide, Olutwatosin; Agyekum, R.S.; Dunn, Thomas; Jones, T.K.; Giannini, H.M.; Weirick, Madison E.; McAllister, Christopher M.; Babady, N. Esther; Kumar, Anita; Widman, Adam; DeWolf, Susan; Boutemine, Sawsan R.; Roberts, Charlotte A.; Budzik, Krista R; Tollett, Susan; Wright, Carla; Perloff, Tara; Sun, Lova; Mathew, Divij; Giles, Josephine R.; Oldridge, Derek A.; Wu, Jennifer E.; Alanio, Cécile; Adamski, Sharon; Garfall, Alfred L.; Vella, Laura A.; Kerr, Samuel J; Cohen, Justine V.; Oyer, Randall A.; Massa, Ryan; Maillard, Ivan; Maxwell, Kara N.; Reilly, John P.; Maslak, P.; Vonderheide, Robert H.; Wolchok, Jedd D.; Hensley, Scott E.; Wherry, E. John; Meyer, Nuala J.; DeMichele, Angela; Vardhana, Santosha A.; Mamtani, Ronac; Huang, Alexander C.

doi:10.1038/s41591-021-01386-7

Cited by 398 publications

(358 citation statements)

References 68 publications

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“…While the T-cell response correlates with the anti-S IgG level at day 42, some patients with B-cell lymphopenia and no humoral response achieved a T-cell response, indicating that immunity to vaccine was not completely abrogated in these patients and that T-cell response could be protective when humoral immunity is deficient. In fact, a recent study reported the crucial role of CD8 + T cells in contributing to the survival of patients with COVID-19 and hematologic cancer, suggesting that CD8 T cells play a key role in limiting SARS-CoV-2, even in the absence of humoral immunity [ 22 ]. These data highlight the role of T-cell responses to vaccination by providing protection in patients with hematologic cancer even in the setting of limited humoral responses.…”

Section: Discussionmentioning

confidence: 99%

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

et al. 2021

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This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.

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Section: Discussionmentioning

confidence: 99%

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

et al. 2021

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“…SARS-CoV-2 mRNA vaccines also induce T cell responses 44,70,71 . Although induction of neutralizing antibodies is likely to be important in vaccine-induced protection, precise correlates of immunity remain to be completely defined and recent evidence also points to a role of T cells in mitigating severe disease upon infection [40][41][42][43]72 . Despite poor antibody responses in most MS-aCD20 patients, all of these patients generated robust CD4 and CD8 T cell responses to SARS-CoV-2 mRNA vaccination suggesting that vaccinating such subjects on B cell immunosuppression is likely to provide some measure of immunity to SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, although the clinical correlates of protection from SARS-CoV-2 infection remain incompletely understood, MS-aCD20 patients appear able to mount productive antiviral CD8 and Th1 CD4 responses, despite suboptimal (or even undetectable) antibody responses. Recent studies in cancer patients indicate an association between T cell responses and better resolution of COVID-19 43 . Thus, it is possible that these vaccine induced T cell responses may confer some protection from severe COVID-19 outcomes in these aCD20-treated patients.…”

Section: Discussionmentioning

confidence: 99%

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Apostolidis

Kakara

Painter

et al. 2021

Preprint

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SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients, and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

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“…In conclusion, we show here that the rapid measurement of cytokine production in whole blood after peptide specific activation is a quick and simple assay that can reliably detect the wide dynamic range of functionally heterogeneous Spike-specific T cell response induced after vaccination or infection in different individuals. Even though T cells cannot prevent infection in the absence of antibodies, their pivotal role in the protection from disease severity has been shown in natural infection of normal (2) (3), oncological patients (7) and in vaccinated individuals (16). As such, since the quantity of Spike-specific T cells cannot be predicted by the simple measurement of antibodies, this higher throughput and simple assay represents a feasible approach to implement in routine testing to complement existing antibody measurements and thus help to define the correlates of protection necessary for the design of current vaccine strategies.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence that antibodies and T cells are required for protection have been generated in monkeys challenged with SARS-CoV-2 (1). Similarly, antibodies and T cells are present in the majority of SARS-CoV-2 infected individuals who control infection without severe symptoms (2–6) and a robust CD8 T cells response is associated with mild disease in oncological patients with humoral defects (7).…”

Section: Introductionmentioning

confidence: 99%

Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected

Tan

Lim

Bert

et al. 2021

Preprint

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Background: Antibodies and T cells cooperate to control virus infections. The definition of the correlates of protection necessary to manage the COVID-19 pandemic, require both immune parameters but the complexity of traditional tests limits virus-specific T cell measurements. Methods: We test the sensitivity and performance of a simple and rapid SARS-CoV-2 Spike-specific T cell test based on stimulation of whole blood with peptides covering the SARS-CoV-2 Spike protein followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2 vaccinated (n=112; 201 samples), convalescent asymptomatic (n=62; 62 samples) and symptomatic (n=68; 115 samples) COVID-19 patients and SARS-CoV-1 convalescent individuals (n=12; 12 samples). Results: The sensitivity of the rapid cytokine whole blood test equates traditional methods of T cell analysis (ELISPOT, Activation Induced Markers). Utilizing this test we observed that Spike-specific T cells in vaccinated preferentially target the S2 region of Spike and that their mean magnitude is similar between them and SARS-CoV-2 convalescents at 3 months after vaccine or virus priming respectively. However, a wide heterogeneity of Spike-specific T cell magnitude characterizes the individual responses irrespective of the time of analysis. No correlation between neutralizing antibody levels and Spike-specific T cell magnitude were found. Conclusions: Rapid measurement of cytokine production in whole blood after peptide activation revealed a wide dynamic range of Spike-specific T cell response after vaccination that cannot be predicted from neutralizing antibody quantities. Both Spike-specific humoral and cellular immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.

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CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer

Cited by 398 publications

References 68 publications

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected

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