Endothelial cell, myeloid, and adaptive immune responses in SARS‐CoV‐2 infection

Degauque, Nicolas; Haziot, Alain; Brouard, Sophie; Mooney, Nuala

doi:10.1096/fj.202100024r

Cited by 16 publications

(12 citation statements)

References 130 publications

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“…One of the most likely implications of CD16 engagement in severe COVID-19 is enhanced T cell degranulation during interac-tion with endothelial cells (Bagnato and Harari, 2015;Degauque et al, 2021). Indeed, based on findings from autopsies in severe COVID-19, T cell infiltration along with endothelial cell injury known as lymphocytic endotheliitis has been observed (Miyazawa, 2020;Varga et al, 2020).…”

Section: Cd16-mediated Degranulation Of Cd8 + T Cells Causes Chemokin...mentioning

confidence: 99%

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Georg

Astaburuaga-García

Bonaguro

et al. 2022

Cell

150

137

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Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16 + T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16 + T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16 + T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16 + cytotoxic T cells. Proportions of activated CD16 + T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

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Section: Cd16-mediated Degranulation Of Cd8 + T Cells Causes Chemokin...mentioning

confidence: 99%

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Georg

Astaburuaga-García

Bonaguro

et al. 2022

Cell

150

137

View full text Add to dashboard Cite

show abstract

“…One of the most likely implications of CD16 engagement in severe COVID-19 is enhanced T cell degranulation during interaction with endothelial cells (Bagnato and Harari, 2015;Degauque et al, 2021). Indeed, based on findings from autopsies in severe COVID-19, T cell infiltration along with endothelial cell injury known as lymphocytic endotheliitis has been observed (Miyazawa, 2020;Varga et al, 2020).…”

Section: Single-cell Transcriptomics Reveal Shift Towards Disproportionally High Cytotoxic and Degranulation Potential Of T Cells In Sevementioning

confidence: 99%

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Georg

Astaburuaga-García

Bonaguro

et al. 2021

Preprint

View full text Add to dashboard Cite

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

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“…Interestingly, semen IL-8 levels remain high (more than double of the cut-off value of 3.8 ng/ml) in most of the enrolled patients also 3 months after COVID-19 healing, suggesting the persistence of an in ammatory condition in the male genital tract that may require further assessment. Similarly, semen levels of 7 cytokines which are part of the SARS-CoV-2 cytokine storm 21 resulted elevated both one and 3 months after COVID-19 recovery in all patients recruited in this study, with the exception of IL-6 which decreased signi cantly after 3 months. In particular, levels of some cytokines (IL-8, IL-1, IL-6, INF gamma and TNF-alpha), resulted higher respect to those found in patients affected by prostatitis (Table 4) 13 , indicating that the in ammatory status of the male genital tract of patients recovering from COVID-19 may be similar or even more compromised.…”

Section: Discussionmentioning

confidence: 54%

Persistent Male Genital Tract Inflammation and Semen Impairment: A Long-Term Effect of SARS-Cov-2 Infection

Gacci

Baldi

Sebastianelli

et al. 2021

Preprint

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Background: Recent reports evidenced an impairment of semen parameters in men affected by coronavirus disease 2019 (COVID-19). In particular, our group previously reported that 1 over 4 COVID-19 healed men were found to be crypto- / azoo-spermic. Moreover, most patients had elevated IL-8 semen levels at sperm analysis. The aim of our study was to assess semen parameters and inflammation by evaluating a panel of sperm cytokine levels (IL-1, IL-4, IL-6, IL-8, IL-17, INF gamma, TNF-alpha) on average 1 month after the second SARS-CoV-2 negative nasopharyngeal swab and 3 months later. Methods: Ten men who showed normozoospermia (n=3), oligozoospermia (n=3) or crypto/azoospermia (n=4) 1 month after healing from COVID-19 in our previous study, were re-called and re-evaluated 3 months after the first semen analysis. Semen parameters were evaluated according to WHO manual and seminal plasma cytokine levels by an ELISA method. Results: At 3-months follow-up, 8 men showed an overall increase of semen parameters compared to levels assessed after 1 month. In particular, of the 4 crypto-/azoo-spermic men 1 month after healing, 2 resulted oligozoospermic, 1 normozoospermic and only 1 remained azoospermic. Two of the 3 oligozoospermic men turned normozoozpermic. Semen cytokine levels were remarkably high one month after healing and remained elevated after 3 months, with the exception of IL-6. Conclusions: This is the first longitudinal, prospective study comparing semen parameters and semen inflammatory markers one and three months after recovering from COVID-19. Our data indicate an overall tendency to an improvement of semen parameters although a genital tract inflammatory condition appears to persist at least 3 months after COVID-19 recovery. This condition could have an impact on male fertility requiring a careful follow up of these patients.

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Endothelial cell, myeloid, and adaptive immune responses in SARS‐CoV‐2 infection

Cited by 16 publications

References 130 publications

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Persistent Male Genital Tract Inflammation and Semen Impairment: A Long-Term Effect of SARS-Cov-2 Infection

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