# Pre-existing and early cellular immune factors correlate with functionally complete protection against primary controlled human SARS-CoV-2 infection

## TL;DR

The study identifies immune factors, like CCL13 and T cells, that may protect against SARS-CoV-2 infection before and shortly after exposure.

## Contribution

The novel finding is that pre-existing mucosal chemokine levels and cross-reactive T cells are linked to protection against SARS-CoV-2 infection.

## Key findings

- Nasopharyngeal CCL13 levels correlate with protection against SARS-CoV-2 infection.
- Cross-reactive T cells and less differentiated NK cells are associated with shorter infection duration.
- CCL13 is a central node connected to pre-existing T cells via CD1c+ dendritic cells.

## Abstract

Identifying host factors that mediate protection against newly-emergent viruses is needed for improved pandemic preparedness. Here, we analysed pre- and early post-exposure immune factors associated with resisting SARS-CoV-2 infection after human challenge in seronegative individuals, using multiplex protein, cytometric and RNA sequencing approaches in the nasopharynx and circulation. Pre-existing cross-reactive antibodies correlate poorly with clinical outcome. Instead, protection is associated with heightened nasopharyngeal CCL13 levels locally produced by conventional dendritic cells and monocytes, along with cross-reactive T cells and less differentiated NK cells. Conditional independence network analysis implicates nasal CCL13 as the central node connected to pre-existing non-structural protein-specific T cells by CD1c+ DCs. In those who became infected, baseline cross-reactive T cell and less differentiated NK cell frequencies also correlate with shorter infection duration. Thus, pre-existing mucosal chemokine levels may promote rapid innate and innate-like responses that effectively block infection. ClinicalTrials.gov identifier NCT04865237.

Human challenge studies with SARS-CoV-2 have shown changes in the innate and adaptive immune response. Here the authors are examining potential correlates of infection in virus challenged recipients by assessing baseline immune parameters and how this predicts virus control.