. 2021 Aug 13;13(8):1605.

doi: 10.3390/v13081605.

The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response

Yolanda Botti-Lodovico¹, Parvathy Nair², Dolo Nosamiefan³, Matthew Stremlau⁴, Stephen Schaffner^{1

5

6}, Sebastian V Agignoae^{1

7}, John Oke Aiyepada⁸, Fehintola V Ajogbasile^{3

9}, George O Akpede^{8

10}, Foday Alhasan¹¹, Kristian G Andersen^{12

13}, Danny A Asogun¹⁴, Oladele Oluwafemi Ayodeji¹⁵, Aida S Badiane¹⁶, Kayla Barnes^{1

6}, Matthew R Bauer¹⁷, Antoinette Bell-Kareem¹⁸, Muoebonam Ekene Benard⁸, Ebo Ohomoime Benevolence⁸, Osiemi Blessing⁸, Chloe K Boehm^{1

19}, Matthew L Boisen²⁰, Nell G Bond¹⁸, Luis M Branco²⁰, Michael J Butts^{1

5}, Amber Carter¹, Andres Colubri^{1

21}, Awa B Deme¹⁶, Katherine C DeRuff¹, Younousse Diédhiou¹⁶, Akhilomen Patience Edamhande⁸, Siham Elhamoumi¹, Emily J Engel¹⁸, Philomena Eromon³, Mosoka Fallah²², Onikepe A Folarin^{3

9}, Ben Fry²³, Robert Garry¹⁸, Amy Gaye¹⁶, Michael Gbakie¹¹, Sahr M Gevao²⁴, Gabrielle Gionet¹, Adrianne Gladden-Young¹, Augustine Goba²⁵, Jules Francois Gomis¹⁶, Anise N Happi³, Mary Houghton¹, Chikwe Ihekwuazu⁸, Christopher Ojemiega Iruolagbe²⁶, Jonathan Jackson²⁷, Simbirie Jalloh²⁵, Jeremy Johnson¹, Lansana Kanneh¹¹, Adeyemi Kayode^{3

9}, Molly Kemball^{1

5}, Ojide Chiedozie Kingsley²⁸, Veronica Koroma¹¹, Dylan Kotliar^{1

5}, Samar Mehta²⁹, Hayden C Metsky¹, Airende Michael⁸, Marzieh Ezzaty Mirhashemi¹, Kayvon Modjarrad³⁰, Mambu Momoh^{25

31}, Cameron A Myhrvold^{1

19}, Okonofua Grace Naregose⁸, Tolla Ndiaye¹⁶, Mouhamadou Ndiaye¹⁶, Aliou Ndiaye¹⁶, Erica Normandin^{1

32}, Ikponmwosa Odia⁸, Judith Uche Oguzie^{3

9}, Sylvanus A Okogbenin⁸, Peter O Okokhere^{8

10

33}, Johnson Okolie³, Idowu B Olawoye^{3

9}, Testimony J Olumade^{3

9}, Paul E Oluniyi^{3

9}, Omigie Omoregie^{8

34}, Daniel J Park¹, Mariétou Faye Paye¹, Brittany Petros^{1

35

36}, Anthony A Philippakis¹, Abechi Priscilla³, Alan Ricks^{37

38}, Anne Rimoin³⁹, John Demby Sandi²⁵, John S Schieffelin⁴⁰, Monica Schreiber⁵, Mame Cheikh Seck¹⁶, Sameed Siddiqui^{1

41}, Katherine Siddle¹, Allison R Smither⁴², Mouhamad Sy¹⁶, Ngayo Sy¹⁶, Christopher H Tomkins-Tinch^{1

5}, Oyewale Tomori⁸, Chinedu Ugwu^{3

9}, Jessica N Uwanibe^{3

9}, Eghosasere Anthonia Uyigue⁸, Dada Ireti Victoria^{3

43}, Anika Vinzé¹, Megan E Vodzak^{1

2}, Nicole Welch^{1

17}, Haja Isatta Wurie²⁵, Daba Zoumarou¹⁶, Donald S Grant^{11

25}, Daouda Ndiaye^{9

16}, Bronwyn MacInnis¹, Pardis C Sabeti^{1

2

5

6

44

45}, Christian Happi^{3

6

9}

Affiliations

¹ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
² Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
³ African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Osun State, Nigeria.
⁴ Equator Labs Incorporated, Washington, DC 20011, USA.
⁵ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁶ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
⁷ Harvard Kennedy School, Cambridge, MA 02138, USA.
⁸ Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
⁹ Department of Biological Sciences, Redeemer's University, Ede, Osun State, Nigeria.
¹⁰ Department of Medicine, Faculty of Clinical Sciences, College of Medicine, Ambrose Alli University, Ekpoma, Edo State, Nigeria.
¹¹ Viral Hemorrhagic Fever Program, Kenema Government Hospital, Ministry of Health and Sanitation, Kenema, Sierra Leone.
¹² Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹³ Scripps Research Translational Institute, La Jolla, CA 92037, USA.
¹⁴ Ambrose Alli University, Ekpoma, Edo State, Nigeria.
¹⁵ Federal Medical Centre, Owo, Ondo State, Nigeria.
¹⁶ Université Cheikh Anta Diop, BP 5005, Dakar, Senegal.
¹⁷ Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
¹⁸ Tulane University Medical Center, New Orleans, LA 70112, USA.
¹⁹ Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
²⁰ Zalgen Labs, Germantown, MD 20876, USA.
²¹ University of Massachusetts Medical School, Worcester, MA 01605, USA.
²² Refuge Place International, Bassa Town, Lower Johnsonville, Liberia.
²³ Fathom Information Design, Boston, MA 02114, USA.
²⁴ University of Sierra Leone, Freetown, Sierra Leone.
²⁵ College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
²⁶ Department of Internal Medicine, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
²⁷ Dimagi, Inc., Cambridge, MA 02139, USA.
²⁸ Department of Medical Microbiology, Alex-Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Ebonyi, Nigeria.
²⁹ Department of Critical Care Medicine, University of Maryland Medical Center, Baltimore, MA 21201, USA.
³⁰ Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
³¹ Eastern Polytechnic College, Kenema, Sierra Leone.
³² Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
³³ Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
³⁴ West African Examinations Council, Yaba, Lagos State, Nigeria.
³⁵ Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
³⁶ Harvard/MIT MD-PhD Program, Boston, MA 02115, USA.
³⁷ MASS Design Group, Boston, MA 02116, USA.
³⁸ Yale School of Architecture, New Haven, CT 06511, USA.
³⁹ Department of Epidemiology, Jonathan and Karing Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA.
⁴⁰ Section of Infectious Disease, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁴¹ Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴² Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁴³ Ikorodu General Hospital, Ikorodu, Lagos State, Nigeria.
⁴⁴ Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴⁵ Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.

PMID: 34452470
PMCID: PMC8402630
DOI: 10.3390/v13081605

The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response

Yolanda Botti-Lodovico et al. Viruses. 2021.

. 2021 Aug 13;13(8):1605.

doi: 10.3390/v13081605.

Authors

Affiliations

¹ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
² Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
³ African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Osun State, Nigeria.
⁴ Equator Labs Incorporated, Washington, DC 20011, USA.
⁵ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁶ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
⁷ Harvard Kennedy School, Cambridge, MA 02138, USA.
⁸ Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
⁹ Department of Biological Sciences, Redeemer's University, Ede, Osun State, Nigeria.
¹⁰ Department of Medicine, Faculty of Clinical Sciences, College of Medicine, Ambrose Alli University, Ekpoma, Edo State, Nigeria.
¹¹ Viral Hemorrhagic Fever Program, Kenema Government Hospital, Ministry of Health and Sanitation, Kenema, Sierra Leone.
¹² Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹³ Scripps Research Translational Institute, La Jolla, CA 92037, USA.
¹⁴ Ambrose Alli University, Ekpoma, Edo State, Nigeria.
¹⁵ Federal Medical Centre, Owo, Ondo State, Nigeria.
¹⁶ Université Cheikh Anta Diop, BP 5005, Dakar, Senegal.
¹⁷ Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
¹⁸ Tulane University Medical Center, New Orleans, LA 70112, USA.
¹⁹ Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
²⁰ Zalgen Labs, Germantown, MD 20876, USA.
²¹ University of Massachusetts Medical School, Worcester, MA 01605, USA.
²² Refuge Place International, Bassa Town, Lower Johnsonville, Liberia.
²³ Fathom Information Design, Boston, MA 02114, USA.
²⁴ University of Sierra Leone, Freetown, Sierra Leone.
²⁵ College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
²⁶ Department of Internal Medicine, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
²⁷ Dimagi, Inc., Cambridge, MA 02139, USA.
²⁸ Department of Medical Microbiology, Alex-Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Ebonyi, Nigeria.
²⁹ Department of Critical Care Medicine, University of Maryland Medical Center, Baltimore, MA 21201, USA.
³⁰ Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
³¹ Eastern Polytechnic College, Kenema, Sierra Leone.
³² Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
³³ Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
³⁴ West African Examinations Council, Yaba, Lagos State, Nigeria.
³⁵ Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
³⁶ Harvard/MIT MD-PhD Program, Boston, MA 02115, USA.
³⁷ MASS Design Group, Boston, MA 02116, USA.
³⁸ Yale School of Architecture, New Haven, CT 06511, USA.
³⁹ Department of Epidemiology, Jonathan and Karing Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA.
⁴⁰ Section of Infectious Disease, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁴¹ Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴² Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁴³ Ikorodu General Hospital, Ikorodu, Lagos State, Nigeria.
⁴⁴ Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴⁵ Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.

PMID: 34452470
PMCID: PMC8402630
DOI: 10.3390/v13081605

Abstract

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE-detected in the Yoruba population of Nigeria-conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the "emerging" nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz's critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.

Keywords: Ebola; LARGE; Lassa fever; Lassa virus; bioinformatics; diagnostic tools; genomic surveillance; infectious disease; pandemic preemption; pandemic response.

PubMed Disclaimer

Conflict of interest statement

Pardis Sabeti is a founder and shareholder of Sherlock Biosciences, and is both on the Board and serves as shareholder of the Danaher Corporation. Anthony Philippakis is a Venture Partner at GV. Jonathan Jackson is CEO of Dimagi. Robert Garry is co-founder, Matthew L. Boisen is director, and Luis M. Branco is co-founder and managing director of Zalgen Labs, a biotechnology company developing countermeasures to emerging viruses. Kristian G. Andersen has received consulting fees and compensated expert testimony on SARS-CoV-2 and the COVID-19 pandemic.

Figures

**Figure 1**
Sentinel will detect pathogens in any setting, from remote rural clinics to hospitals, and unknown pathogens will be identified and characterized at regional genome centers. Through a cloud-based system, Sentinel will share this information and connect healthcare workers, researchers, and disease control officials to track and predict threats. Finally, Sentinel will empower all stakeholders through a codified pandemic preemption system that can be scaled around the world.

See this image and copyright information in PMC

References

1. Sabeti P.C., Varilly P., Fry B., Lohmueller J., Hostetter E., Cotsapas C., Xie X., Byrne E.H., McCarroll S.A., Gaudet R., et al. Genome-Wide Detection and Characterization of Positive Selection in Human Populations. Nature. 2007;449:913–918. doi: 10.1038/nature06250. - DOI - PMC - PubMed
1. Kunz S., Rojek J.M., Perez M., Spiropoulou C.F., Oldstone M.B.A. Characterization of the Interaction of Lassa Fever Virus with Its Cellular Receptor α-Dystroglycan. J. Virol. 2005;79:5979–5987. doi: 10.1128/JVI.79.10.5979-5987.2005. - DOI - PMC - PubMed
1. Kunz S., Rojek J.M., Kanagawa M., Spiropoulou C.F., Barresi R., Campbell K.P., Oldstone M.B.A. Posttranslational Modification of α-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding. J. Virol. 2005;79:14282–14296. doi: 10.1128/JVI.79.22.14282-14296.2005. - DOI - PMC - PubMed
1. Troup J.M., White H.A., Fom A.L.M.D., Carey D.E. An Outbreak of Lassa Fever on the Jos Plateau, Nigeria, in January–February 1970: A Preliminary Report. Am. J. Trop. Med. Hyg. 1970;19:695–696. doi: 10.4269/ajtmh.1970.19.695. - DOI - PubMed
1. McCormick J.B., Fisher-Hoch S.P. Lassa Fever. In: Oldstone M.B.A., editor. Arenaviruses I: The Epidemiology, Molecular and Cell Biology of Arenaviruses. Springer; Berlin/Heidelberg, Germany: 2002. pp. 75–109. Current Topics in Microbiology and Immunology.

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The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response

Affiliations

The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Grants and funding

LinkOut - more resources

Full Text Sources

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