Postdoctoral position at the Pasteur Institute, Paris: Role of T cell responses in Long COVID

A post-doctoral position is available to study the immune mechanisms involved in Long COVID. The successful applicant will join the team of Lisa Chakrabarti at the Pasteur Institute in Paris. The position is funded for 3 years by the ANRS-MIE.

A significant proportion of patients with COVID-19 still experiences symptoms more than 3 months after an initial infection with SARS-CoV-2. Persisting or reemerging symptoms are varied, with a predominance of asthenia, neurocognitive impairment, and dyspnea. The persistence of these debilitating symptoms defines the Long COVID syndrome, which is now considered a serious public health concern. Importantly, the etiology of Long COVID remains unknown. We propose to test the hypothesis that an inefficient antiviral T cell response underlies Long COVID. The rationale is that suboptimal T cell immunity could promote viral persistence, with residual virus in turn causing localized tissue damage and persistent inflammation.

The study will involve an in-depth analysis of SARS-CoV-2 specific T cell responses in Long COVID patients and convalescents, based on spectral flow cytometry analyses on previously collected blood samples. The repertoire of SARS-CoV-2-specific T cell receptors (TCRs) will be compared between groups by single cell approaches. The efficiency of the T cell response will be evaluated at the molecular level, by analyzing the affinity of the most prevalent TCRs specific for immunodominant SARS-CoV-2 epitopes. CD4+ T cell/ B cell interactions will be evaluated in a novel lymph-node-on-chip system, to explore why a subset of Long COVID patients do not seroconvert. Clinical evaluation and sensitive ddPCR viral load measurements will be performed by collaborating teams. An integrated analysis of these parameters will help determine whether inefficient T cell responses correlate with residual inflammation and viral persistence. The postdoctoral fellow will benefit from the availability of biobanked samples, the access to state-of-the art technological platforms, and the very dynamic environment of the Pasteur Institute.