Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients.

It is critical to protect immunocompromised patients against COVID-19 with effective SARS-CoV-2 vaccination as they have an increased risk of developing severe disease. This is challenging, however, since effective mRNA vaccination requires the successful cooperation of several components of the innate and adaptive immune systems, both of which can be severely affected/deficient in immunocompromised people. In this article, we first review current knowledge on the immunobiology of SARS-COV-2 mRNA vaccination in animal models and in healthy humans. Next, we summarize data from early trials of SARS-COV-2 mRNA vaccination in patients with secondary or primary immunodeficiency. These early clinical trials identified common predictors of lower response to the vaccine such as anti-CD19, anti-CD20 or anti-CD38 therapies, low (naive) CD4+ T-cell counts, genetic or therapeutic Bruton tyrosine kinase deficiency, treatment with antimetabolites, CTLA4 agonists or JAK inhibitors, and vaccination with BNT162b2 versus mRNA1273 vaccine. Finally, we review the first data on third dose mRNA vaccine administration in immunocompromised patients and discuss recent strategies of temporarily holding/pausing immunosuppressive medication during vaccination.

Increased IL-10-producing regulatory T cells are characteristic of severe cases of COVID-19.

OBJECTIVES: The pandemic spread of the coronavirus SARS-CoV-2 is due, in part, to the immunological properties of the host-virus interaction. The clinical presentation varies from individual to individual, with asymptomatic carriers, mild-to-moderate-presenting patients and severely affected patients. Variation in immune response to SARS-CoV-2 may underlie this clinical variation. METHODS: Using a high-dimensional systems immunology platform, we have analysed the peripheral blood compartment of 6 healthy individuals, 23 mild-to-moderate and 20 severe COVID-19 patients. RESULTS: We identify distinct immunological signatures in the peripheral blood of the mild-to-moderate and severe COVID-19 patients, including T-cell lymphopenia, more consistent with peripheral hypo- than hyper-immune activation. Unique to the severe COVID-19 cases was a large increase in the proportion of IL-10-secreting regulatory T cells, a lineage known to possess anti-inflammatory properties in the lung. CONCLUSION: As IL-10-secreting regulatory T cells are known to possess anti-inflammatory properties in the lung, their proportional increase could contribute to a more severe COVID-19 phenotype. We openly provide annotated data (https://flowrepository.org/experiments/2713) with clinical correlates as a systems immunology resource for the COVID-19 research community.