# People who use drugs show no increase in pre-existing T-cell cross-reactivity toward SARS-CoV-2 but develop a normal polyfunctional T-cell response after standard mRNA vaccination

## TL;DR

People who use drugs do not have higher pre-existing T-cell immunity to SARS-CoV-2 but can develop strong immune responses after standard mRNA vaccination.

## Contribution

Demonstrates that standard mRNA vaccination elicits robust T-cell responses in people who use drugs despite opioid-related immune suppression.

## Key findings

- PWUD did not show increased pre-existing T-cell cross-reactivity to SARS-CoV-2.
- Standard mRNA vaccination induced strong polyfunctional CD4+ and CD8+ T-cell responses in PWUD.
- Vaccine-induced immune responses in PWUD were comparable to those in control groups.

## Abstract

People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4+ and CD8+ T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.