Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

Enocsson, Helena; Idoff, Cornelia; Gustafsson, Annette; Govender, Melissa; Hopkins, Francis R.; Larsson, Marie; Nilsdotter-Augustinsson, Åsa; Sjöwall, Johanna

doi:10.3389/fmed.2021.791716

Cited by 32 publications

(53 citation statements)

References 66 publications

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“…These have been shown to have a positive correlation with the development of pulmonary lesions during early COVID-19, and consequently with severe COVID-19 and related respiratory complications [70, 71]. We recently found an association of soluble urokinase Plasminogen Activator Receptor with COVID-19 severity, and length of hospitalization [72]. Additionally, lymphopenia was observed in many of the COVID-19 patients in our cohort at inclusion (i.e., at hospitalization), and is a common clinical observation [73–76] that may likely be attributed to the cells relocating or consequently dying at this stage of the disease.…”

Section: Discussionmentioning

confidence: 99%

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Govender

Hopkins

Göransson

et al. 2022

Preprint

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COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Govender

Hopkins

Göransson

et al. 2022

Preprint

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“…Examples from non-neoplastic pathological conditions associated to enhanced SuPAR expression include the focal segmental glomerulosclerosis, a disease in which high SuPAR plasma levels predict disease progression to end-stage renal failure ( Winnicki et al, 2019 ). It was recently reported that high levels of blood SuPAR predict severe/critical Covid-19 disease and are associated with length of hospital stay ( Enocson et al, 2021 ).…”

Section: Diagnostic and Terapeutic Aspectsmentioning

confidence: 99%

Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View

Alfano

Franco

Stoppelli

2022

Front. Cell Dev. Biol.

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Urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycosyl-phosphatidyl-inositol anchored (GPI) membrane protein. The uPAR primary ligand is the serine protease urokinase (uPA), converting plasminogen into plasmin, a broad spectrum protease, active on most extracellular matrix components. Besides uPA, the uPAR binds specifically also to the matrix protein vitronectin and, therefore, is regarded also as an adhesion receptor. Complex formation of the uPAR with diverse transmembrane proteins, including integrins, formyl peptide receptors, G protein-coupled receptors and epidermal growth factor receptor results in intracellular signalling. Thus, the uPAR is a multifunctional receptor coordinating surface-associated pericellular proteolysis and signal transduction, thereby affecting physiological and pathological mechanisms. The uPAR-initiated signalling leads to remarkable cellular effects, that include increased cell migration, adhesion, survival, proliferation and invasion. Although this is beyond the scope of this review, the uPA/uPAR system is of great interest to cancer research, as it is associated to aggressive cancers and poor patient survival. Increasing evidence links the uPA/uPAR axis to epithelial to mesenchymal transition, a highly dynamic process, by which epithelial cells can convert into a mesenchymal phenotype. Furthermore, many reports indicate that the uPAR is involved in the maintenance of the stem-like phenotype and in the differentiation process of different cell types. Moreover, the levels of anchor-less, soluble form of uPAR, respond to a variety of inflammatory stimuli, including tumorigenesis and viral infections. Finally, the role of uPAR in virus infection has received increasing attention, in view of the Covid-19 pandemics and new information is becoming available. In this review, we provide a mechanistic perspective, via the detailed examination of consolidated and recent studies on the cellular responses to the multiple uPAR activities.

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“…This pilot study is a part of a prospective, observational cohort study described elsewhere [ 18 ], implemented during August 2020 to May 2021, and involving hospitalized adult patients with COVID-19.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Specific Antibody Response and T Cell-Immunity in Immunocompromised Patients up to Six Months Post COVID: A Pilot Study

Sjöwall

Hjorth

Gustafsson

et al. 2022

JCM

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COVID-19 generates SARS-CoV-2-specific antibodies in immunocompetent individuals. However, in immunocompromised patients, the humoral immunity following infection may be impaired or absent. Recently, the assessment of cellular immunity to SARS-CoV-2, both following natural infection and vaccination, has contributed new knowledge regarding patients with low or no antibody responses. As part of a prospective cohort study which included hospitalized patients with COVID-19, we identified immunocompromised patients and compared them with age- and sex-matched immunocompetent patients regarding co-morbidities, biomarkers of COVID-19 and baseline viral load by real-time PCR in nasopharyngeal swabs. Spike and nucleocapsid antibody responses were analyzed at inclusion and after two weeks, six weeks and six months. Plasma immunoglobulin G (IgG) levels were quantified, lymphocyte phenotyping was performed, and SARS-CoV-2 specific CD4 and CD8 T cell responses after in vitro antigen stimulation were assessed at six months post infection. All patients showed IgG levels above or within reference limits. At six months, all patients had detectable SARS-CoV-2 anti-spike antibody levels. SARS-CoV-2 specific T cell responses were detected in 12 of 12 immunocompetent patients and in four of six immunocompromised patients. The magnitude of long-lived SARS-CoV-2 specific T cell responses were significantly correlated with the number of CD4 T cells and NK cells. Determining the durability of the humoral and cellular immune response against SARS-CoV-2 in immunocompromised individuals could be of importance by providing insights into the risk of re-infection and the need for vaccine boosters.

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Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

Cited by 32 publications

References 66 publications

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View

SARS-CoV-2 Specific Antibody Response and T Cell-Immunity in Immunocompromised Patients up to Six Months Post COVID: A Pilot Study

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