The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

SARS-CoV-2 infection and vaccination generates enormous host response heterogeneity and an age-dependent loss of immune response quality. How the pre-exposure T cell repertoire contributes to this heterogeneity is poorly understood. We combined analysis of SARS-CoV-2-specific CD4+ T cells pre- and post-vaccination with longitudinal T cell receptor tracking. We identified strong pre-exposure T cell variability that correlated with subsequent immune response quality and age. High-quality responses, defined by strong expansion of high-avidity spike-specific T cells, high interleukin 21 production, and specific immunoglobulin G, depended on an intact naïve repertoire and exclusion of pre-existing memory T cells. In the elderly, T cell expansion from both compartments was severely compromised. Our results reveal that an intrinsic defect of the CD4+ T cell repertoire causes the age-dependent decline of immune response quality against SARS-CoV-2 and highlight the need for alternative strategies to induce high-quality T cell responses against newly arising pathogens in the elderly. Graphical Determinants of immune response quality to SARS-CoV-2 remain poorly defined. Saggau et al. examine spike-specific naïve and memory T cells pre- and post-vaccination and track pre-existing memory T cell receptors. They define T cell parameters of high-quality vaccine responses and identify high pre-existing memory and low naïve T cell contributions as predictors of low-quality responses, particularly in the elderly.

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids (preprint)

Several studies have pointed to retinal involvement in COVID 19 disease, yet many questions remain regarding the ability of SARS CoV 2 to infect and replicate in retinal cells and its effects on the retina. Here we have used human stem cell derived retinal organoids to study retinal infection by the SARS CoV 2 virus. Indeed, SARS CoV 2 can infect and replicate in retinal organoids, as it is shown to infect different retinal lineages, such as retinal ganglion cells and photoreceptors. SARS CoV 2 infection of retinal organoids also induces the expression of several inflammatory genes, such as interleukin 33, a gene associated with acute COVID 19 disease and retinal degeneration. Finally, we show that the use of antibodies to block the ACE2 receptor significantly reduces SARS CoV 2 infection of retinal organoids, indicating that SARS CoV 2 infects retinal cells in an ACE2 dependent manner. These results suggest a retinal involvement in COVID 19 and emphasize the need to monitor retinal pathologies as potential sequelae of long COVID.