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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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SARS-CoV-2 Proteins
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    The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses

    Authors: F. Konstantin Fohse; Busranur Geckin; Gijs J. Overheul; Josephine van de Maat; Gizem Kilic; Ozlem Bulut; Helga Dijkstra; Heidi Lemmers; S. Andrei Sarlea; Maartje Reijnders; Jacobien Hoogerwerf; Jaap ten Oever; Elles Simonetti; Frank L. van de Veerdonk; Leo A. B. Joosten; Bart L. Haagmans; Reinout van Crevel; Yang Li; Ronald P. van Rij; Corine GeurtsvanKessel; Marien I. de Jonge; Jorge Dominguez-Andres; Mihai G. Netea

    doi:10.1101/2021.05.03.21256520 Date: 2021-05-06 Source: medRxiv

    The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 MESHD vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 HGNC and TLR7 HGNC/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

    Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection MESHD

    Authors: Martina Severa; Roberta Antonina Diotti; Marilena Paola Etna; Fabiana Rizzo; Stefano Fiore; Daniela Ricci; Marco Iannetta; Alessandro Sinigaglia; Alessandra Lodi; Nicasio Mancini; Elena Criscuolo; Massimo Clementi; Massimo Andreoni; Stefano Balducci; Luisa Barzon; Paola Stefanelli; Nicola Clementi; Eliana Coccia

    doi:10.1101/2021.04.17.440278 Date: 2021-04-19 Source: bioRxiv

    SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 MESHD ( COVID-19 MESHD) progression. Indeed, critically ill MESHD patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure MESHD. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7 HGNC/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19 MESHD. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2 HGNC-indipendent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 HGNC marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected MESHD subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 MESHD display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 MESHD patients.

    Association of Toll-like receptor 7 variants with life-threatening COVID-19 MESHD disease in males

    Authors: Chiara Fallerini; Sergio Daga; Stefania Mantovani; Elisa Benetti; Aurora Pujol; Nicola Picchiotti; Agatha Schluter; Laura Planas-Serra; Jesus Troya; Margherita Baldassarri; Francesca Fava; Serena Ludovisi; Francesco Castelli; Maria Eugenia Quiros-Roldan; Massimo Vaghi; Stefano Rusconi; Matteo Siano; Maria Bandini; Simone Furini; Francesca Mari; - GEN-COVID Multicenter Study; Alessandra Renieri; Mario U Mondelli; Elisa Frullanti

    doi:10.1101/2020.11.19.20234237 Date: 2020-11-27 Source: medRxiv

    Background: COVID-19 MESHD clinical presentation ranges from asymptomatic to fatal outcome. This variability is due in part to host genome specific mutations. Recently, two families in which COVID-19 MESHD segregates like an X-linked recessive monogenic disorder MESHD environmentally conditioned by SARS-CoV-2 have been reported leading to identification of loss-of-function variants in TLR7 HGNC. Objective: We sought to determine whether the two families represent the tip of the iceberg of a subset of COVID-19 MESHD male patients. Methods: We compared male subjects with extreme phenotype selected from the Italian GEN-COVID cohort of 1178 SARS-CoV-2-infected MESHD subjects (<60y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on the young male subset, picking up TLR7 HGNC as the most important susceptibility gene. Results: Rare TLR7 HGNC missense variants were predicted to impact on protein function in severely affected males and in none of the asymptomatic subjects. We then investigated a similar white European cohort in Spain, confirming the impact of TRL7 variants. A gene expression profile analysis in peripheral blood mononuclear cells after stimulation with TLR7 HGNC agonist demonstrated a reduction of mRNA level of TLR7 HGNC, IRF7 HGNC, ISG15 HGNC, IFN-[a] and IFN-{gamma HGNC} in COVID-19 MESHD patients compared with unaffected controls demonstrating an impairment in type I and II INF responses. Conclusion: Young males with TLR7 HGNC loss-of-function mutations and severe COVID-19 MESHD in the two reported families represent only a fraction of a broader and complex host genome situation. Specifically, missense mutations in the X-linked recessive TLR7 disorder MESHD TLR7 HGNC disorder may significantly contribute to disease susceptibility in up to 4% of severe COVID-19 MESHD.

    IL-33 HGNC expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 MESHD convalescent individuals

    Authors: Michal A Stanczak; David E Sanin; Petya Apostolova; Gabriele Nerz; Dimitrios Lampaki; Maike Hofmann; Daniel Steinmann; Robert Thimme; Gerhard Mittler; Cornelius F Waller; Edward J Pearce; Erika L Pearce

    doi:10.1101/2020.07.09.20148056 Date: 2020-07-10 Source: medRxiv

    Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 spike PROTEIN glycoprotein aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever MESHD. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 HGNC agonist- activation revealed an increased population of IL-6+TNF-IL-1 HGNC{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33 HGNC, IL-6 HGNC, IFNa2 HGNC, and IL-23 HGNC expression in seropositive individuals. IL-33 HGNC correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33 HGNC- producing cells. IL-33 HGNC is associated with pulmonary infection MESHD and chronic diseases like asthma MESHD and COPD, but its role in COVID-19 MESHD is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid MESHD ( BALF MESHD) from patients with mild to severe COVID-19 MESHD revealed a population of IL-33 HGNC-producing cells that increases with disease. Together these findings show that IL-33 HGNC production is linked to SARS-CoV- 2 infection MESHD and warrant further investigation of IL-33 HGNC in COVID-19 MESHD pathogenesis and immunity.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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