Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes

Renner, Karl; Schwittay, Tobias; Chaabane, Sophia; Gottschling, J.; Müller, Christine; Tiefenböck, Charlotte; Salewski, Jan-Niklas; Winter, Frederike; Buchtler, Simone; Balam, Saidou; Malfertheiner, Maximilian; Lubnow, Matthias; Lunz, Dirk; Graf, Bernhard M.; Hitzenbichler, Florian; Hanses, Frank; Poeck, Hendrik; Kreutz, Marina; Orsó, Evelyn; Burkhardt, Ralph; Niedermair, Tanja; Brochhausen, Christoph; Gessner, André; Salzberger, Bernd; Mack, Matthias

doi:10.1038/s41467-021-23334-2

Cited by 13 publications

(15 citation statements)

References 39 publications

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“…Our data corroborated a role for altered erythropoiesis in COVID-19 with elevated circulating cfDNA originating from erythroid progenitors, especially in severe disease. Another feature of COVID-19 is lymphopenia in the peripheral blood (T, B, and NK cells), indicating impairment of adaptive immunity 67 . Absolute lymphocyte count was also low in SOT COVID-19 patients and our methylome analysis corroborated these findings with low/undetectable cfDNA levels from CD4 + T cells and CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Integrated cell-free DNA and cytokine analysis uncovers distinct tissue injury and immune response patterns in solid organ transplant recipients with COVID-19

Andargie

Zhou

Karaba

et al. 2022

Preprint

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COVID-19 pathogenesis is associated with an exuberant inflammatory response. However, the tissue injury pattern and immune response in solid-organ transplant recipients (SOTRs) taking immunosuppressive therapy have not been well characterized. Here, we perform both cfDNA and cytokine profiling on plasma samples to map tissue damage, including allograft injury and delineate underlying immunopathology. We identified injuries from multiple-tissue types, including hematopoietic cells, vascular endothelium, hepatocyte, adipocyte, pancreas, kidney, heart, and lung in SOTRs with COVID-19 that correlates with disease severity. SOTRs with COVID-19 have higher plasma levels of cytokines such as IFN-λ1, IFN-γ, IL-15, IL-18 IL-1RA, IL-6, MCP-2, and TNF-α as compared to healthy controls, and the levels of GM-CSF, IL-15, IL-6, IL-8, and IL-10 were associated with disease severity in SOTRs. Strikingly, IFN-λ and IP-10 were markedly increased in SOTRs compared to immunocompetent patients with COVID-19. Correlation analyses showed a strong association between monocyte-derived cfDNA and inflammatory cytokines/chemokines in SOTRs with COVID-19. Moreover, compared to other respiratory viral infections, COVID-19 induced pronounced injury in hematopoitic, vascular endothelial and endocrine tissues. Allograft injury, measured as donor-derived cfDNA was elevated in SOTRs with COVID-19, including allografts distant from the primary site of infection. Allograft injury correlated with inflammatory cytokines and cfDNA from immune cells. Furthermore, longitudinal analysis identified a gradual decrease of cfDNA and inflammatory cytokine levels in patients with a favorable outcome. Our findings highlight distinct tissue injury and cytokine features in SOTRs with COVID-19 that correlate with disease severity.

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Section: Discussionmentioning

confidence: 99%

Integrated cell-free DNA and cytokine analysis uncovers distinct tissue injury and immune response patterns in solid organ transplant recipients with COVID-19

Andargie

Zhou

Karaba

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The impact of viruses on the activation mechanisms of cellular stress in immunocompetent cells is also significant, as it causes polyclonal activation and apoptosis of lymphocytes (primarily T cells), pathological activation of macrophages, and immunosuppression [41].…”

Section: General Characteristics Of Sars-cov-2 Infectionmentioning

confidence: 99%

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

Gusev

Sarapultsev

Соломатина

et al. 2022

IJMS

181

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The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus’s protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2’s ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

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“…T cell anergy is already present in non-ventilated COVID-19 patients and strongly associated with virus persistence and reversible with clinical recovery [25].…”

Section: T Cell Anergymentioning

confidence: 99%

Anergy in COVID-19 Infected and COVID-19 vaccinee

2022

J Int Pers COVID-19

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death protein-1 (PD-1) [2]. In this opinion reduced immune cell function was defined and anergic cells were visualized, their potential role played in COVID-19 was mapped. Mechanism of B cell AnergyYarkoni and associates [15] and Waterman and Cambier [12] have been thoroughly reviewing the multiple possible mechanisms for induction of B cell anergy. Going through these reviews, a hypothesis was arise from a collective viewing to the presented facts that may unify the mentioned mechanisms and was phrased as in the following; 1. B cell face chronic antigen stimulation

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Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes

Cited by 13 publications

References 39 publications

Integrated cell-free DNA and cytokine analysis uncovers distinct tissue injury and immune response patterns in solid organ transplant recipients with COVID-19

Integrated cell-free DNA and cytokine analysis uncovers distinct tissue injury and immune response patterns in solid organ transplant recipients with COVID-19

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

Anergy in COVID-19 Infected and COVID-19 vaccinee

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