Unbiased spectral cytometry immunome characterization predicts COVID-19 mRNA vaccine failure in older adults and patients with lymphoid malignancies

ABSTRACT COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8 + T-cells, B-cells, NK cells, monocytes and CD45RA + CCR7 - Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note, up to 7 subsets were found within the CD45RA + CCR7 - Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV- 2 mRNA vaccines. SUMMARY An in depth and unbiased spectral cytometry characterization of the immune system before and after COVID-19 vaccination can predict not just subsequent PCR-confirmed infection, but also COVID-induced hospitalization in immune compromised patients.