https://insight.jci.org/articles/view/146701 f

https://insight.jci.org/articles/view/146701

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further indicating that cytokine levels are dysregulated in patients with COVID-19 after clinical symptom remission.

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cells were collected for exhaustion

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positive for the LAG3 exhaustion marker,

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Notably, we observed an overall reversal of the COVID-19 serum–induced increase in costimulatory and exhaustion marker expression on both CD4+ and CD8+ T cells following addition of blocking antibodies to cell cultures (Figure 2C and Supplemental Figure 3, A and . In particular, the expression of PD-1 and ICOS on CD4+ T cells and that of CD127 and CD40L on CD8+ T cells showed a marked decrease when the majority of blocking antibodies were added, both individually and as a pool, to PBMCs cultured with serum obtained from patients with COVID-19 (Figure 2C and Supplemental Figure 3, A and . Overall, these findings suggest that high levels of serum cytokines, at least in part, account for the T cell exhaustion observed in patients who recovered from COVID-19.

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T cells from patients who recovered from COVID-19 are dysfunctional. Given the persistent T cell activation/exhaustion observed in patients who recovered from COVID-19,

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long haulers is exhausted T cells that don't want to respond to what they are supposed to respond to.
These T cells have a lot of PD-1 receptors on their surfaces.
Giving PD-1 blockers, restores these cells back to normal.

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In vitro PD-1 blockade restores T cell function. Based on these results, we hypothesized that PD-1 blockade could counteract post–COVID-19 immune abnormalities (Figure 4A). We therefore sought to determine whether PD-1 blockade, achieved by use of a clinically relevant anti–PD-1 blocking mAb, would revert the exhaustion status of T cells and restore their functional activity in response to specific and nonspecific stimulation.

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Moreover, PD-1 blockade in PBMCs isolated from patients with COVID-19 resulted in a decrease in the percentage of exhausted T cells (Figure 4, C–J). Taken together, our data indicate that, in T cells isolated from patients with COVID-19 upon PD-1 immune checkpoint blockade, T cell immune response and phenotype improve.

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We thus demonstrate that PD-1 blockade enhances the anti–SARS-CoV-2–specific immune response and reinforces PBMC-mediated SARS-CoV-2 antiviral activity.

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