Lymphopenia-induced T cell proliferation is a hallmark of severe COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a broad clinical presentation ranging from asymptomatic infection to fatal disease. Different features associated with the immune response to SARS-CoV-2, such as hyperinflammation and reduction of peripheral CD8+ T cell counts are strongly associated with severe disease. Here, we confirm the reduction in peripheral CD8+ T cells both in relative and absolute terms and identify T cell apoptosis and migration into inflamed tissues as possible mechanisms driving peripheral T cell lymphopenia. Furthermore, we find evidence of elevated serum interleukin-7, thus indicating systemic T cell paucity and signs of increased T cell proliferation in patients with severe lymphopenia. Following T cell lymphopenia in our pseudo-longitudinal time course, we observed expansion and recovery of poly-specific antiviral T cells, thus arguing for lymphopenia-induced T cell proliferation. In summary, this study suggests that extensive T cell loss and subsequent T cell proliferation are characteristic of severe COVID-19.

A distinct innate immune signature marks progression from mild to severe COVID-19

“…SARS-CoV mouse models have shown that the recruitment of proinflammatory monocytes to the lungs, promoted by delayed type I IFN signaling, drives immunopathology, and interestingly, a scRNA-seq study in bronchoalveolar lavage fluid of SARS-CoV-2 infected individuals found an accumulation of monocyte-derived macrophages and high levels of inflammatory cytokines in severe patients. 16 , 22 Several factors, such as a maladapted IFN response or an inadequate T cell response in severe COVID-19, 46 may contribute to the dysregulated monocyte response in severely ill patients. The latter could be due to suboptimal viral control, although T cells have also been shown to control an overactive innate response in a murine coronavirus infection model.…”

“…Routine flow cytometry for NK cell quantification was performed on all samples in the accredited immunological laboratory at the University Hospital Zurich, as previously described. 46 The cohort characteristics and a selection of the Olink dataset are also shown in Adamo et al. 46 describing the T cell response of this cohort.…”

“… 46 The cohort characteristics and a selection of the Olink dataset are also shown in Adamo et al. 46 describing the T cell response of this cohort.…”

T cell response to SARS-CoV-2 infection in humans: A systematic review

“…This suggests an important relationship between pathogenesis and the circulating T cell pool. Observed lymphopaenia in adult COVID-19 patients is likely to be multifactorial in origin, with redistributive effects, apoptotic loss [ 74 ], and possibly reduced mobilisation of lymphocytes from bone marrow, all playing a part. Prior work has also shown an association between IL-6 production and blockade of lymphopoiesis; although the extent to which this mechanism operates in COVID-19 has yet to be investigated [ 75 ].…”

Illuminating the immunopathology of SARS‐CoV‐2

“…The adaptive arm of the immune system appears to be crippled with significant T cell loss or lymphopenia (especially CD8 + T cells) in the peripheral blood of severe patients‐ both due to extensive apoptosis (preferentially of CD8 + T cells) as well as T cell migration to the lungs (Adamo et al, 2020). Despite the significant T cell loss, highly activated peripheral T cells were found in a subgroup of hospitalized COVID‐19 patients, and T cell activation was associated with more severe disease and organ failure (Mathew et al, 2020).…”