Clinical Research Directory

Understanding the Determinants of Mucosal Immunity and Optimizing the Diagnosis of Infection With SARS-CoV-2 Variants

Sponsor: Institut Pasteur

Summary

One of the current health challenges in the face of the COVID-19 pandemic that started in Wuhan in 2019, and still responsible for successive waves, is to better understand and diagnose the infection. The new variants - delta, then omicron, which appeared in November 2021 and then their sub-variants BA.2, then BA.4 and 5, and more recently BQ.1 and the sub-variant XBB.1.5 are increasingly transmissible and responsible for some degree of immune escape. Hence the importance of a better understanding of infection- or vaccine-induced immunity in order to optimize existing prophylactic or therapeutic strategies, or even to develop new, more effective ones. Mucosal immunity could play a particularly important role in interrupting the infection cycle at the entry point of the virus. The key role of innate immunity has been demonstrated in particular, via interferons and the composition of the microbiota. Humoral immunity is the best documented. However, it tends to be eroded within a few months. On the other hand, cellular immunity is more stable over time and would largely explain the decrease in severe forms of the disease in vaccinated individuals. The collection of biological resources that will be built up during this study will also allow us to optimize or develop new diagnostic methods, necessary as a complement to vaccination, to effectively slow down the spread of the pandemic and reduce the severity of its impact on the population. The improvement of diagnostic methods will in turn improve the understanding of the infection by providing increasingly reliable information on the characteristics of an infection, its quantification, its dynamics, and its resolution, especially since these parameters will be compared, at any time during the study, with reference methods and the immunological status of the subject. The main significant improvements expected in the field of SARS-CoV-2 diagnosis are notably the improvement of performance (reduction of false negatives in RT-PCR on nasopharyngeal samples), acceptability, simplicity of implementation in the field, and the capacity to test transmission. The objective of this study is to identify and characterize SARS-CoV-2 infection and host response, particularly mucosal immunity.

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