TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies

Ploeg, Kattria van der; Kirosingh, Adam; Mori, Diego AM; Chakraborty, Saborni; Hu, Zicheng; Sievers, Benjamin L.; Jacobson, Karen; Bonilla, Hector; Parsonnet, Julie; Andrews, Jason R; Press, Kathleen D.; Ty, Maureen; Ruiz-Betancourt, Daniel; Parte, Lauren de la; Tan, Gene S.; Blish, Catherine A.; Takahashi, Saki; Rodríguez-Barraquer, Isabel; Greenhouse, Bryan; Singh, Upinder; Wang, Taia T.; Jagannathan, Prasanna

doi:10.1016/j.xcrm.2022.100640

Cited by 35 publications

(25 citation statements)

References 66 publications

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“…T-cells that produce more than one of the three cytokine of interest have been considered as to be important in response to viral infections, including influenza ( 43 , 44 ). Moreover, in convalescent COVID-19 patients this polyfunctional cytokine profile has been observed suggesting a possible rapid recall response ( 45 – 47 ).…”

Section: Discussionmentioning

confidence: 93%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

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BackgroundThe mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.MethodsThe aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled “responding T-cells”, those cells that produced at least one of the three cytokines of interest, and “triple positive T-cells”, those cells that produced simultaneously all the three cytokines.ResultsThe cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).ConclusionIn pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

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Section: Discussionmentioning

confidence: 93%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

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“…One study which investigated the presence of COVID-19 antibodies in post-COVID-19 infected persons found that Fc-dependent antibody activity in mild to moderate COVID-19 infections persisted longer than neutralization antibodies after a SARS-CoV-2 infection [ 16 ]. Other studies have reported that antibody activity against COVID-19 re-infection persisted for 4–14 months after the index COVID-19 infection [ 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. This could explain no further outbreaks 1 year after the program was ended in this factory.…”

Section: Discussionmentioning

confidence: 99%

Integrative Effects between a Bubble and Seal Program and Workers’ Compliance to Health Advice on Successful COVID-19 Transmission Control in a Factory in Southern Thailand

Kongkamol

Ingviya

Chusri

et al. 2022

IJERPH

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Applying health measures to prevent COVID-19 transmission caused disruption of businesses. A practical plan to balance public health and business sustainability during the pandemic was needed. Herein, we describe a “Bubble and Seal” (B&S) program implemented in a frozen seafood factory in southern Thailand. We enrolled 1539 workers who lived in the factory dormitories. First, the workers who had a high fatality risk were triaged by RT-PCR tests, quarantined and treated if they had COVID-19. Newly diagnosed or suspected COVID-19 workers underwent the same practices. The non-quarantined workers were regulated to work and live in their groups without contact across the groups. Workers’ personal hygiene and preventive measures were strongly stressed. Between the 6th and 9th weeks of the program, the post-COVID-19 infection status (PCIS) of all participants was evaluated by mass COVID-19 antibody or RT-PCR tests. Finally, 91.8% of the workers showed positive PCIS, which was above the number required for program exit. Although no workers had received a vaccination, there was only one case of severe COVID-19 pneumonia, and no evidence of COVID-19 spreading to the surrounding communities. Implementation of the B&S program and workers’ adherence to health advice was the key to this success.

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“…Expression of CD40L by T cells is known to be crucial for affinity maturation and classswitching 43,44 . Moreover, the frequencies of specific IFNγ-and TNFa-producing CD4+ T cells correlate with the persistence of MBCs specific for the spike protein and with high levels of SARS-CoV-2-neutralizing antibodies 45,46 .…”

Section: T Cell Phenotype and Function In The Four Groups Of Cvids Pa...mentioning

confidence: 97%

The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies

Mortari

Pulvirenti

Marcellini

et al. 2022

Preprint

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In patients with common variable immune deficiencies, primary vaccination followed by two booster doses is recommended for protection against COVID-19. Seroconversion has been shown in 60% of patients. We have no information on whether serum antibodies reflect the generation of durable immune memory. In a longitudinal study on 47 common variable immune deficiencies patients who received the third and fourth vaccine dose, we show that the measurement of specific antibodies is not sufficient to predict the establishment of immune memory and the ability to respond to antigen re-exposure. Our results indicate that the combination of antibodies and memory B cells responses represents a more reliable read-out of vaccine immune efficacy in vulnerable patients. This analysis may not only identify individuals remaining unprotected after vaccination and unable to respond to additional booster doses, but also address the search for the underlying immune defect and suggest patient-tailored management strategies.

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TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies

Cited by 35 publications

References 66 publications

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Integrative Effects between a Bubble and Seal Program and Workers’ Compliance to Health Advice on Successful COVID-19 Transmission Control in a Factory in Southern Thailand

The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies

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