#Immune #response to #SARS-CoV-2 in #HCWs following a #COVID19 outbreak: a prospective longitudinal study (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology | Available online 6 August 2020, 104575 | In Press, Journal Pre-proof

Immune response to SARS-CoV-2 in health care workers following a COVID-19 outbreak: a prospective longitudinal study

Sara Fill Malfertheiner a,d, Susanne Brandstetter b,d, Samra Roth b, Susanne Harner b, Heike Buntrock-Döpke b,d, Antoaneta A. Toncheva b, Natascha Borchers b, Rudolf Gruber c, Andreas Ambrosch c, Michael Kabesch b,d, Sebastian Häusler a

a University Department of Obstetrics and Gynecology at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany; b University Children’s Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany; c Institute of Laboratory Medicine, Microbiology and Hygiene, Hospital of the Order of St. John, Regensburg, Germany; d WECARE Research and Development Campus Regensburg at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany

Received 17 July 2020, Accepted 30 July 2020, Available online 6 August 2020.

DOI: https://doi.org/10.1016/j.jcv.2020.104575

 

Abstract

Objective

Currently, little is known about the progression of an immune response against SARSCoV- 2 upon infection or sub-infection-exposure over time. We examined the serologic response in healthcare workers up to 12 weeks after a well-documented and contained outbreak and compared results with findings from earlier serologic testing in the same population.

Methods

This study followed 166 health care workers of the University Perinatal Care Center, Regensburg, Germany, for up to 12 weeks. 27 of the subjects had previously tested positive for the presence of SARS-CoV-2 by PCR testing and developed COVID-19. Serologic responses were tested with two independent commercially available test kits.

Results

77.8% of COVID-19 study subjects developed a specific IgG-response over the course of the 12-week study, while none of the COVID-19 contact groups had a detectable IgG response. Amongst most COVID-19 patients the values of detectable IgG-responses significantly increased over time as confirmed with both tests, while that of positive IgA responses decreased. Between the number of reported symptoms and antibody responses in COVID-19 patients no correlation was found and no new cases of seroconversion were identified in asymptomatic coworkers with negative PCR during the outbreak.

Conclusions

Immune response after COVID-19 increases significantly over time but still approximately 22% of COVID-19 patients did not mount a measurable serologic immune response within 60 days. Exposed co-workers did not develop any relevant antibody levels at all. We conclude that immunity after infection increases over time, but the antibody response does not develop reliably in all infected people.

Keywords: SARS-CoV-2; COVID-19; Serology; Immunology.

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#Systems-level #immunomonitoring from acute to recovery phase of #severe #COVID19 (Cell Rep Med., abstract)

[Source: Cell Reports Medicine, full page: (LINK). Abstract, edited.]

Systems-level immunomonitoring from acute to recovery phase of severe COVID-19

Lucie Rodriguez,  Pirkka T. Pekkarinen, Tadepally Lakshmikanth, Ziyang Tan, Camila Rosat Consiglio, Christian Pou, Yang Chen, Constantin Habimana Mugabo, Ngoc Anh Nguyen, Kirsten Nowlan, Tomas Strandin, Lev Levanov, Jaromir Mikes, Jun Wang, Anu Kantele, Jussi Hepojoki, Olli Vapalahti, Santtu Heinonen, Eliisa Kekäläinen, Petter Brodin

Open Access | Published: August 05, 2020 |  DOI: https://doi.org/10.1016/j.xcrm.2020.100078

 

Highlights

  • Immunomonitoring from acute to recovery phase COVID-19
  • An IFNg – Eosinophil axis precede lung hyperinflammation
  • Basophils modulate SARS-CoV2 IgG responses
  • A shared trajectory of immunological recovery in COVID-19

 

Summary

Severe disease of SARS-CoV2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses required to capture cellular interactions. Here we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ – Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

Accepted: July 28, 2020 – Received in revised form: June 25, 2020 – Received: June 3, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.xcrm.2020.100078

Copyright © 2020 The Author(s).

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.

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Dysregulated #adaptive immune #response contributes to #severe #COVID19 (Cell Res., summary)

[Source: Cell Research, full page: (LINK). Summary, edited.]

Dysregulated adaptive immune response contributes to severe COVID-19

Kuai Yu, Jingjing He, Yongjian Wu, Baosong Xie, Xuefei Liu, Bo Wei, Haibo Zhou, Bingliang Lin, Zhixiang Zuo, Wen Wen, Wenxiong Xu, Bin Zou, Lai Wei, Xi Huang & Penghui Zhou

Cell Research (2020)

___

Dear Editor, The outbreak of the new coronavirus SARS-CoV-2 has resulted in a global pandemic. Due to the lack of a specific drug against this virus, the current clinical management of this disease mainly depends on supportive care to reduce inflammatory responses and to keep the lung functioning.1 Understanding the underlying immunopathology of coronavirus disease 2019 (COVID-19) is therefore of paramount importance for improving the current treatment. In this study, we found a distinct feature of adaptive immunity in severely affected patients, the coincidence of impaired cellular and enhanced humoral immune responses, suggesting that dysregulated adaptive immune responses advanced severe COVID-19. Interestingly, expression of Prothymosin alpha (PTMA), the proprotein of Thymosin alpha-1 (Tα1), was increased in a group of CD8 T memory stem cells accumulated during severe disease. We further showed that Tα1 slightly reduced T cell activation in vitro and promoted proliferation of effector T cells. Moreover, Tα1 treatment relieved the lymphopenia in COVID-19 patients. Our data suggest that early intervention of adaptive immune response might be critical for the prevention of severe COVID-19.

(…)

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.

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Impaired immune cell #cytotoxicity in #severe #COVID-19 is #IL6 dependent (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent

Alessio Mazzoni,1 Lorenzo Salvati,1 Laura Maggi,1 Manuela Capone,1 Anna Vanni,1 Michele Spinicci,1,2 Jessica Mencarini,1,2 Roberto Caporale,3 Benedetta Peruzzi,3 Alberto Antonelli,1 Michele Trotta,2 Lorenzo Zammarchi,1,2 Luca Ciani,1 Leonardo Gori,1 Chiara Lazzeri,4 Andrea Matucci,5 Alessandra Vultaggio,5 Oliviero Rossi,5 Fabio Almerigogna,1,5 Paola Parronchi,1,6 Paolo Fontanari,7 Federico Lavorini,1,8 Adriano Peris,4 Gian Maria Rossolini,1,9 Alessandro Bartoloni,1,2 Sergio Romagnani,1 Francesco Liotta,1,6 Francesco Annunziato,1,3 and Lorenzo Cosmi1,6

First published May 28, 2020

 

Abstract

BACKGROUND.

Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.

METHODS.

We performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.

RESULTS.

Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A–expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.

CONCLUSION.

The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.

FUNDING.

This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the “Excellence Departments 2018–2022 Project”) derived from Ministero dell’Istruzione, dell’Università e della Ricerca (Italy).

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Tocilizumab; Immunology.

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Acute #SARS-CoV-2 infection impairs #dendritic cell and T cell responses (Immunity, abstract)

[Source: Immunity, full page: (LINK). Abstract, edited.]

Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses

Runhong Zhou, Kelvin Kai-Wang To, Yik-Chun Wong, Li Liu, Biao Zhou, Xin Li, Haode Huang, Yufei Mo, Tsz-Yat Luk, Thomas Tsz-Kan Lau, Pauline Yeung, Wai-Ming Chan, Alan Ka-Lun Wu, Kwok-Cheung Lung, Owen Tak-Yin Tsang, Wai-Shing Leung, Ivan Fan-Ngai Hung, Kwok-Yung Yuen,  Zhiwei Chen

Published: August 03, 2020 | DOI: https://doi.org/10.1016/j.immuni.2020.07.026

 

Highlights

  1. Acute SARS-CoV-2 infection results in broad immune cell reduction
  2. Both dendritic cells and T cells are functionally impaired
  3. Neutralizing antibodies are rapidly and abundantly generated
  4. RBD- and NP-specific T cells are delayed at the acute stage

 

Summary

The SARS-CoV-2 pandemic has resulted in millions of infections yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, NK, monocyte and dendritic cell (DC). DCs were significantly reduced with functional impairment, and cDC:pDC ratios were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks post symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, may contribute to acute COVID-19 pathogenesis and have implications for vaccine development.

Accepted: July 27, 2020 – Received in revised form: June 24, 2020 – Received: May 19, 2020

Publication stage In Press Accepted Manuscript

The authors declared no conflict of interests.

Identification DOI: https://doi.org/10.1016/j.immuni.2020.07.026

Copyright © 2020 Elsevier Inc.

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.

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#Selective and cross-reactive #SARS-CoV-2 T cell #epitopes in unexposed #humans (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

Jose Mateus1, Alba Grifoni1, Alison Tarke1, John Sidney1, Sydney I. Ramirez1,3, Jennifer M. Dan1,3, Zoe C. Burger3, Stephen A. Rawlings3, Davey M. Smith3, Elizabeth Phillips2, Simon Mallal2, Marshall Lammers1, Paul Rubiro1, Lorenzo Quiambao1, Aaron Sutherland1, Esther Dawen Yu1, Ricardo da Silva Antunes1, Jason Greenbaum1, April Frazier1, Alena J. Markmann4, Lakshmanane Premkumar5, Aravinda de Silva5, Bjoern Peters1,3, Shane Crotty1,3, Alessandro Sette1,3,*,†, Daniela Weiskopf1,*,†

1 Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. 2 Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA 6150, Australia. 3 Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA. 4 Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. 5 Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

*Corresponding author. Email: alex@lji.org (A.S.); daniela@lji.org (D.W.)
† These authors contributed equally to this work.

Science  04 Aug 2020: eabd3871 | DOI: 10.1126/science.abd3871

 

Abstract

Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of pre-existing memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.

Keywords: SARS-CoV-2; COVID-19; Coronavirus; Immunology.

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Longitudinal #dynamics of the neutralizing #antibody #response to #SARS-CoV-2 infection (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Longitudinal dynamics of the neutralizing antibody response to SARS-CoV-2 infection

Kai Wang, Quan-Xin Long, Hai-Jun Deng, Jie Hu, Qing-Zhu Gao, Gui-Ji Zhang, Chang-Long He, Lu-Yi Huang, Jie-Li Hu, Juan Chen, Ni Tang, Ai-Long Huang

Clinical Infectious Diseases, ciaa1143, https://doi.org/10.1093/cid/ciaa1143

Published: 03 August 2020

 

Abstract

Background

Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of SARS-CoV-2-specific neutralizing antibodies (NAbs) in COVID-19 patients.

Methods

Blood samples (n=173) were collected from 30 COVID-19 patients over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs, using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines.

Results

SARS-CoV-2-specific NAb titers were low for the first 7–10 d after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 d (IQR 24–59 d) after symptom onset. NAb titers in 93·3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34·8% (IQR 19·6–42·4%). NAb titers increased over time in parallel with the rise in IgG antibody levels, correlating well at week 3 (r = 0·41, p & 0·05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including SCF, TRAIL, and M-CSF.

Conclusions

These data provide useful information regarding dynamic changes in NAbs in COVID-19 patients during the acute and convalescent phases.

SARS-CoV-2, neutralizing antibodies, longitudinal dynamics, COVID-19, serological immune response

Issue Section: Major Article

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© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: SARS-CoV-2; COVID-19; Neutralizing antibodies; Immunology.

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Fruitful neutralizing #antibody #pipeline brings hope to defeat #SARS-Cov-2 (Trends Pharmacol Sci., abstract)

[Source: Trends of Pharmacological Sciences, full page: (LINK). Abstract, edited.]

Fruitful neutralizing antibody pipeline brings hope to defeat SARS-Cov-2

Alex Renn, Ying Fu, Xin Hu, Matthew D. Hall, Anton Simeonov

Published: July 31, 2020 | DOI: https://doi.org/10.1016/j.tips.2020.07.004

 

Highlights

  • We are currently experiencing an explosion of antibody research against COVID-19 that include neutralizing antibodies against SARS-CoV-2 and therapeutic antibodies against COVID-19 associated hyperinflammation.
  • 8 neutralizing antibodies against SARS-CoV-2, LY-CoV555, JS016, REGN-COV2, TY027, BRII-196, BRII-198, CT-P59 and SCTA01, have now entered clinical trials (as of July 28th, 2020).
  • SARS-CoV-2 may develop resistance to neutralizing antibodies through accumulating spontaneous mutations.
  • The neutralizing antibodies also may show antibody-dependent enhancement (ADE) and amplify disease progression.

 

Abstract

With the recent spread of SARS-CoV-2 infecting over 16 million people worldwide as of July 28th, 2020, causing more than 650,000 deaths, there is a desperate need for therapeutic agents and vaccines. Building on the knowledge of the previous outbreaks of SARS-CoV-1 and MERS, the development of therapeutic antibodies and vaccines for COVID-19 is taking place at an unprecedented speed. In this review, the current efforts made toward developing neutralizing antibodies against COVID-19 are summarized. We also highlight the importance of having such a fruitful antibody development pipeline that will be helpful in combatting the potential escape plans of SARS-CoV-2 including somatic mutations and antibody-dependent enhancement (ADE).

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies; Immunology.

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#Immunoserologic #detection and #diagnostic relevance of cross-reactive auto-antibodies in #COVID19 patients (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunoserologic detection and diagnostic relevance of cross-reactive auto-antibodies in COVID-19 patients

María Teresa Schiaffino, Marisa Di Natale, Elena García-Martínez, Joaquín Navarro, José Luis Muñoz-Blanco, Pablo Demelo-Rodríguez, Paloma Sánchez-Mateos

The Journal of Infectious Diseases, jiaa485, https://doi.org/10.1093/infdis/jiaa485

Published: 01 August 2020

 

Abstract

During the COVID-19 pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients. The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections. We describe 12 patients positive for the cross-reactive Ab, compared to a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion. Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for auto-reactive mediated complications such as thrombotic or neurologic events.

COVID-19, Autoimmunity, Autoantibody, Immunofluorescence, Molecular Mimicry

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.

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Distinct early #serological #signatures track with #SARS-CoV-2 #survival (Immunity, abstract)

[Source: Immunity, full page: (LINK). Abstract, edited.]

Distinct early serological signatures track with SARS-CoV-2 survival

Caroline Atyeo #, Stephanie Fischinger #, Tomer Zohar #, Matthew D. Slein, John Burke, Carolin Loos, Denise J. McCulloch, Kira L. Newman, Caitlin Wolf, Jingyou Yu, Kiel Shuey, Jared Feldman, Blake Marie Hauser, Tim Caradonna, Aaron Schmidt, Todd J. Suscovich, Caitlyn Linde, Yongfei Cai, Dan Barouch, Edward T. Ryan, Richelle C. Charles, Douglas Lauffenburger, Helen Chu, Galit Alter

Published: July 30, 2020 | DOI: https://doi.org/10.1016/j.immuni.2020.07.020

 

Highlights

  • Limited early differences across groups were observed in titers and neutralization
  • Five antibody features collectively could differentiate convalescents and deceased
  • A shift in the balance of spike versus nucleocapsid immunity separated the groups
  • Spike-specific phagocytic and complement fixing activity was enriched in convalescents

 

Summary

As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection whereas others rapidly progress and die. While the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2–specific humoral responses on a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. While no differences in SARS-CoV-2-specific IgG levels were observed, spike–specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant S-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies, point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.

Accepted: July 23, 2020 – Received in revised form: June 29, 2020 – Received: May 22, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.immuni.2020.07.020

Copyright © 2020 Published by Elsevier Inc.

Keywords: SARS-CoV-2; COVID-19; Serology; Immunology.

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