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Introduction
The evidence on COVID-19 is being produced at high speed, so it is challenging for decision-makers to keep up. It seems appropriate, then, to put into practice a novel approach able to provide the scientific community and other interested parties with quality evidence that is actionable, and rapidly and efficiently produced.

Methods and analysis
We designed a protocol for multiple parallel systematic reviews and overviews of systematic reviews in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for primary studies and systematic reviews that answer different questions related to COVID-19 using both a centralized repository (Epistemonikos database) and a manual search in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We will also search for literature in several other sources. At least two researchers will independently undertake the selection of studies, data extraction, and assessment of the quality of the included studies. We will synthesize data for each question using meta-analysis, when possible, and we will prepare Summary of Findings tables according to the GRADE approach. All the evidence will be organized in an open platform (L·OVE - Living OVerview of Evidence) that will be continuously updated using artificial intelligence and a broad network of experts.

Ethics and dissemination
No ethics approval is considered necessary. The results of these articles will be widely disseminated via peer-reviewed publications, social networks, and traditional media, and will be sent to relevant international organizations discussing this topic.

Authors: Gabriel Rada[1,2,3], Francisca Verdugo-Paiva[1,2], Camila Ávila[1], Macarena Morel-Marambio[2], Rocío Bravo-Jeria[2], Franco Pesce[4], Eva Madrid[5,6], Ariel Izcovich[7], COVID-19 L·OVE Working Group [8], COVID-19 L·OVE Working Group

Colaboradores: Rafael Almendra-Pegueros , Carlos Alvares, Gabriel Araneda, Camila Ávila, Eduard Baladia, Sandra Bohorquez-Blanco, Rocío Bravo-Jeria, Kristian Buhring-Bonacich, Cynthia Carrasco-Carré, Natalia Carvajal-Juliá, Cristóbal Cuadrado, Catalina Ferrada, Iván Flores, Juan Víctor Ariel Franco, Roberto Garnham , Roland Garroz, Andrés Gempeler-Rojas, Lina Goez-Mogollon, Cristián Gonzalez-Alarcón, Ariel Izcovich, Eva Madrid, Maria Marqués, Patricia Martínez, Nicolás Meza, Macarena Morel-Marambio, Josefina Neumann, Paulina Ojeda, Pablo Olguín, Luis Ortiz-Muñoz, Franco Pesce , Eduardo Peña, Ana Beatriz Pizarro, Daniel Poloni, Pablo Prieto, Marcelo Pérez, Javier Pérez-Bracchiglione , Giordano Pérez-Gaxiola , Gabriel Rada, Martín Ragusa, María Ximena Rojas, Azucena Santillan-Garcia, Javiera Sepúlveda, Luz Angela Torres-López, Gabriela Urrea, Manuel Vargas-Peirano , Catalina Verdejo, Francisca Verdugo-Paiva, Laura Vergara, Juan Carlos Villar

Affiliation:
[1] Fundación Epistemonikos, Santiago, Chile
[2] UC Evidence Center, Cochrane Chile Associated Center, Pontificia Universidad Católica de Chile, Santiago, Chile
[3] Internal Medicine Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Living Knowledge, Santiago, Chile
[5] Interdisciplinary Centre for Health Studies (CIESAL), Cochrane Chile
[6] Associated Centre, Universidad de Valparaíso, Valparaíso, Chile
[7] Internal Medicine Service, German Hospital, Buenos Aires, Argentina
[8] COVID-19 L·OVE Working Group

E-mail: radagabriel@epistemonikos.org

Author address:
[1] Holanda 895
Providencia
Santiago
Chile.

Citation: Rada G, Verdugo-Paiva F, Ávila C, Morel-Marambio M, Bravo-Jeria R, Pesce F, et al. Evidence synthesis relevant to COVID-19: a protocol for multiple systematic reviews and overviews of systematic reviews. Medwave 2020;20(3):e7867 doi: 10.5867/medwave.2020.03.7867

Submission date: 26/3/2020

Acceptance date: 30/3/2020

Publication date: 1/4/2020

Origin: Not commissioned.

Type of review: Internally reviewed with fast track.

 

Errata

1. Error in the list of contributors is corrected | Link |

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1. World Health Organization. Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. World Health Organization; 2020. [Internet] | Link |
2. Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Feb;91:264-266. | CrossRef | PubMed |
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5. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Mar 10. pii: S0883-9441(20)30390-7. | CrossRef | PubMed |
6. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949. | CrossRef | PubMed |
7. Chen Jun, Liu Danping. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of Zhejiang University (Medical Science). 2020 [Accessed March 26] 49(1):0-0 [Internet] | Link |
8. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. | CrossRef | PubMed |
9. Akl EA, Haddaway NR, Rada G, Lotfi T. Evidence synthesis 2.0: when systematic, scoping, rapid, living, and overviews of reviews come together. J Clin Epidemiol. 2020 Mar 4. pii: S0895-4356(19)30986-2. | CrossRef | PubMed |
10. Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol. 2018 Nov 19;18(1):143. | CrossRef | PubMed |
11. Borah R, Brown AW, Capers PL, Kaiser KA. Analysis of the time and workers needed to conduct systematic reviews of medical interventions using data from the PROSPERO registry. BMJ Open. 2017 Feb 27;7(2):e012545. | CrossRef | PubMed |
12. Roberts I, Ker K. How systematic reviews cause research waste. Lancet. 2015 Oct 17;386(10003):1536. | CrossRef | PubMed |
13. Shojania KG, Sampson M, Ansari MT, Ji J, Doucette S, Moher D. How quickly do systematic reviews go out of date? A survival analysis. Ann Intern Med. 2007 Aug 21;147(4):224-33. | PubMed |
14. Pussegoda K, Turner L, Garritty C, Mayhew A, Skidmore B, Stevens A, et al. Systematic review adherence to methodological or reporting quality. Syst Rev. 2017 Jul 19;6(1):131. | CrossRef | PubMed |
15. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Jan 1;4:1. | CrossRef | PubMed |
16. Epistemonikos database methods. Santiago: Foundation Epistemonikos (Accessed on March 26, 2020). [Internet] | Link |
17. Methods for the special L·OVE of Coronavirus infection. Santiago: Foundation Epistemonikos (Accessed on March 26, 2020). [Internet] | Link |
18. Cochrane Effective Practice and Organisation of Care (EPOC). EPOC Resources for review authors. 2017 (Accessed March 26). [Internet] | Link |
19. Hemingway H, Croft P, Perel P, Hayden JA, Abrams K, Timmis A, et al. Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes. BMJ. 2013 Feb 5;346:e5595. | CrossRef | PubMed |
20. Jin X, Pang B, Zhang J, Liu Q, Yang Z, Feng J, et al. Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID), Engineering. 2020 March 18 (Accessed March 26). [Internet] | Link |
21. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol. 2011 Apr;64(4):395-400. | CrossRef | PubMed |
22. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. J Clin Epidemiol. 2013 Feb;66(2):158-72. | CrossRef | PubMed |
23. Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, et al. GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes. J Clin Epidemiol. 2013 Feb;66(2):173-83. | CrossRef | PubMed |
24. L·OVE platform. Santigo: Foundation Epistemonikos (Accessed on March 26, 2020). [Internet] | Link |
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26. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016 Oct 12;355:i4919. | CrossRef | PubMed |
27. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011 Oct 18;155(8):529-36. | CrossRef | PubMed |
28. Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013 Feb 19;158(4):280-6. | CrossRef | PubMed |
29. Moons KGM, Wolff RF, Riley RD, Whiting PF, Westwood M, Collins GS,et al. PROBAST: A Tool to Assess Risk of Bias and Applicability of Prediction Model Studies: Explanation and Elaboration. Ann Intern Med. 2019 Jan 1;170(1):W1-W33. | CrossRef | PubMed |
30. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017 Sep 21;358:j4008. | CrossRef | PubMed |
31. Guyatt GH, Ebrahim S, Alonso-Coello P, Johnston BC, Mathioudakis AG, Briel M, et al. GRADE guidelines 17: assessing the risk of bias associated with missing participant outcome data in a body of evidence. J Clin Epidemiol. 2017 Jul;87:14-22. | CrossRef | PubMed |
32. Review Manager (RevMan). Version 5.3.5 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. [Computer program]

World Health Organization. Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. World Health Organization; 2020. [Internet] | Link |

Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Feb;91:264-266. | CrossRef | PubMed |

Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020 Feb 19. pii: S1473-3099(20)30120-1. | CrossRef | PubMed |

Ioannidis JPA. Coronavirus disease 2019: the harms of exaggerated information and non-evidence-based measures. Eur J Clin Invest. 2020 Mar 23:e13223. | CrossRef | PubMed |

Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Mar 10. pii: S0883-9441(20)30390-7. | CrossRef | PubMed |

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949. | CrossRef | PubMed |

Chen Jun, Liu Danping. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of Zhejiang University (Medical Science). 2020 [Accessed March 26] 49(1):0-0 [Internet] | Link |

Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. | CrossRef | PubMed |

Akl EA, Haddaway NR, Rada G, Lotfi T. Evidence synthesis 2.0: when systematic, scoping, rapid, living, and overviews of reviews come together. J Clin Epidemiol. 2020 Mar 4. pii: S0895-4356(19)30986-2. | CrossRef | PubMed |

Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol. 2018 Nov 19;18(1):143. | CrossRef | PubMed |

Borah R, Brown AW, Capers PL, Kaiser KA. Analysis of the time and workers needed to conduct systematic reviews of medical interventions using data from the PROSPERO registry. BMJ Open. 2017 Feb 27;7(2):e012545. | CrossRef | PubMed |

Roberts I, Ker K. How systematic reviews cause research waste. Lancet. 2015 Oct 17;386(10003):1536. | CrossRef | PubMed |

Shojania KG, Sampson M, Ansari MT, Ji J, Doucette S, Moher D. How quickly do systematic reviews go out of date? A survival analysis. Ann Intern Med. 2007 Aug 21;147(4):224-33. | PubMed |

Pussegoda K, Turner L, Garritty C, Mayhew A, Skidmore B, Stevens A, et al. Systematic review adherence to methodological or reporting quality. Syst Rev. 2017 Jul 19;6(1):131. | CrossRef | PubMed |

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Jan 1;4:1. | CrossRef | PubMed |

Epistemonikos database methods. Santiago: Foundation Epistemonikos (Accessed on March 26, 2020). [Internet] | Link |

Methods for the special L·OVE of Coronavirus infection. Santiago: Foundation Epistemonikos (Accessed on March 26, 2020). [Internet] | Link |

Cochrane Effective Practice and Organisation of Care (EPOC). EPOC Resources for review authors. 2017 (Accessed March 26). [Internet] | Link |

Hemingway H, Croft P, Perel P, Hayden JA, Abrams K, Timmis A, et al. Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes. BMJ. 2013 Feb 5;346:e5595. | CrossRef | PubMed |

Jin X, Pang B, Zhang J, Liu Q, Yang Z, Feng J, et al. Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID), Engineering. 2020 March 18 (Accessed March 26). [Internet] | Link |

Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol. 2011 Apr;64(4):395-400. | CrossRef | PubMed |

Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. J Clin Epidemiol. 2013 Feb;66(2):158-72. | CrossRef | PubMed |

Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, et al. GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes. J Clin Epidemiol. 2013 Feb;66(2):173-83. | CrossRef | PubMed |

L·OVE platform. Santigo: Foundation Epistemonikos (Accessed on March 26, 2020). [Internet] | Link |

Epistemonikos Foundation. Collaboratron™ [Software], 2020. [Internet] | Link |

Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016 Oct 12;355:i4919. | CrossRef | PubMed |

Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011 Oct 18;155(8):529-36. | CrossRef | PubMed |

Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013 Feb 19;158(4):280-6. | CrossRef | PubMed |

Moons KGM, Wolff RF, Riley RD, Whiting PF, Westwood M, Collins GS,et al. PROBAST: A Tool to Assess Risk of Bias and Applicability of Prediction Model Studies: Explanation and Elaboration. Ann Intern Med. 2019 Jan 1;170(1):W1-W33. | CrossRef | PubMed |

Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017 Sep 21;358:j4008. | CrossRef | PubMed |

Guyatt GH, Ebrahim S, Alonso-Coello P, Johnston BC, Mathioudakis AG, Briel M, et al. GRADE guidelines 17: assessing the risk of bias associated with missing participant outcome data in a body of evidence. J Clin Epidemiol. 2017 Jul;87:14-22. | CrossRef | PubMed |

Review Manager (RevMan). Version 5.3.5 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. [Computer program]