urgent needs to accelerate the race for covid 19 therapeutics CORD-Papers-2022-06-02 (Version 1)

Title: Urgent needs to accelerate the race for COVID-19 therapeutics
Published: 2021-05-23
Journal: EClinicalMedicine
DOI: 10.1016/j.eclinm.2021.100911
DOI_URL: http://doi.org/10.1016/j.eclinm.2021.100911
Author Name: Batista Carolina
Author link: https://covid19-data.nist.gov/pid/rest/local/author/batista_carolina
Author Name: Shoham Shmuel
Author link: https://covid19-data.nist.gov/pid/rest/local/author/shoham_shmuel
Author Name: Ergonul Onder
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ergonul_onder
Author Name: Hotez Peter
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hotez_peter
Author Name: Bottazzi Maria Elena
Author link: https://covid19-data.nist.gov/pid/rest/local/author/bottazzi_maria_elena
Author Name: Figueroa J Peter
Author link: https://covid19-data.nist.gov/pid/rest/local/author/figueroa_j_peter
Author Name: Gilbert Sarah
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gilbert_sarah
Author Name: Gursel Mayda
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gursel_mayda
Author Name: Hassanain Mazen
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hassanain_mazen
Author Name: Kang Gagandeep
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kang_gagandeep
Author Name: Kaslow David
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kaslow_david
Author Name: Kim Jerome H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kim_jerome_h
Author Name: Lall Bhavna
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lall_bhavna
Author Name: Larson Heidi
Author link: https://covid19-data.nist.gov/pid/rest/local/author/larson_heidi
Author Name: Naniche Denise
Author link: https://covid19-data.nist.gov/pid/rest/local/author/naniche_denise
Author Name: Sheahan Timothy
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sheahan_timothy
Author Name: Wilder Smith Annelies
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wilder_smith_annelies
Author Name: Sow Samba O
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sow_samba_o
Author Name: Yadav Prashant
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yadav_prashant
Author Name: Strub Wourgaft Nathalie
Author link: https://covid19-data.nist.gov/pid/rest/local/author/strub_wourgaft_nathalie
sha: c9b739ec805866ed125868f812f4cfbd6c7fba93
license: cc-by-nc-nd
license_url: https://creativecommons.org/licenses/by-nc-nd/4.0/
source_x: Elsevier; Medline; PMC
source_x_url: https://www.elsevier.com/https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/
pubmed_id: 34036254
pubmed_id_url: https://www.ncbi.nlm.nih.gov/pubmed/34036254
pmcid: PMC8141354
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141354
url: https://www.sciencedirect.com/science/article/pii/S2589537021001917 https://doi.org/10.1016/j.eclinm.2021.100911 https://www.ncbi.nlm.nih.gov/pubmed/34036254/ https://api.elsevier.com/content/article/pii/S2589537021001917
has_full_text: TRUE
Keywords Extracted from Text Content: LMICs baricitinib MEB https://www.journals.elsevier.com/eclinicalmedicine hydroxychloroquine BMGF CB Janssen Pharmaceuticals PH Amplyx F2G left bamlanivimab COVID-19 convalescent plasma tocilizumab lopinavir/ritonavir patient HL reports grants COVID19 Merck Vaccine CEPI ScienceDirect EClinicalMedicine Immunome T2 laterstage imdevimab Cidara coronavirus EUA OE SK biosciences ViiV patients Ansun BioPharma casirivimab developers/trial woman SS BL SS reports grants RECOVERY ACT-A. 8 ivermectin etesevimab dexamethasone ANTI-COV coronavirus vaccines pillar GlaxoSmithKline Acidophil oxygen Bill oral antiviral agents COVID-19 vaccine NS-W
Extracted Text Content in Record: First 5000 Characters:On December 8, 2020, a 91-year-old woman made history as the first person to receive the COVID-19 vaccine in the United Kingdom. Worldwide vaccination coverage will take time, especially in lowmiddle-income countries (LMICs) where access to coronavirus vaccines is limited and health systems are ill equipped to deal with sustained pressures associated with COVID-19. Meanwhile, hospital and critical care capacity will remain strained and basic therapies, including oxygen, are in urgent short supply. 1 COVID-19 has disproportionately impacted the world's poorest and most vulnerable, posing additional challenges in achieving the Sustainable Development Goals. 2 In addition to basic supportive therapies, there are still not enough effective therapeutic interventions widely available. There remains an urgent need to develop efficacious COVID-19 therapeutics to prevent severity and mortality, and to forestall the collapse of overburdened health systems in resource-limited settings. It has been over a year since the world's biomedical community began to contend this novel coronavirus. Having effective treatments to target COVID-19 stages would lead to significant benefits. These include treatments to (i) prevent the development of infections (ii) prevent disease progression, and (iii) reduce mortality. To better understand COVID-19 therapeutics, much had to be learned about the virus, disease evolution, how to conduct trials under pandemic conditions, and how to link testing and treatment strategies. Two major therapeutic strategies based on disease pathophysiology were developed: antiviral agents, which aim to stop virus spread in the respiratory tract, and host-directed therapeutics (anti-inflammatory and immunomodulators), which have mostly become laterstage interventions aimed at preventing downstream consequences of severe COVID-19. Initial efforts focused primarily on stemming the high mortality rates in critical patients and in drug repurposing. Several drugs demonstrated mechanistic plausibility and were initially tested for their in vitro activity on virus replication. Antiparasitic drugs, such as Contents lists available at ScienceDirect EClinicalMedicine journal homepage: https://www.journals.elsevier.com/eclinicalmedicine hydroxychloroquine and ivermectin, and antiviral drugs, such as lopinavir/ritonavir, were widely used while clinical trials were being conducted. Despite early hopes, results from multiple clinical studies did not meet expectations, hence not supporting use of these drugs 3 especially for severe cases. However, despite lack of evidence, 4 indiscriminate prescription with these drugs in many countries 5 has fueled misinformation and controversy. According to WHO, 6 more than 2800 COVID-19 drug trials have been registered thus far. International platforms, such as RECOVERY, SOLIDARITY, PRINCIPLE, DISCOVERY, REMAP-CAP, TOGETHER, ANTI-COV, are leading efforts to recruit large numbers of subjects while pharmaceutical companies are conducting their own trials. Global coordination, increased funding, comparable endpoints, open-source data repository and real-time information sharing will be key to meeting increasing demands for effective COVID-19 therapeutics. Although much has been learned, questions remain about predictive factors for disease evolution and best approaches across the COVID-19 continuum, ranging from asymptomatic or mildly symptomatic patients to those hospitalized or who are critically ill, and to those living with long-term sequela of infection, as well as the impact of emerging variants on treatment efficacy. Therefore, widely available safe and effective antiviral therapies, administered early could help alleviate patient burden and potentially diminish the need for hospitalization. To date only few drugs have been approved, registered, received Emergency Use Authorization (EUA) or qualified for WHO Emergency Use Listing. These include dexamethasone, remdesivir, bamlanivimab administered with etesevimab, casirivimab plus imdevimab, convalescent plasma, and the combination of baricitinib and remdesivir. Variable recommendations by different entities reflect the challenges to analyze, standardize and translate evidence into clinical guidelines including updates for immunomodulators such as tocilizumab and medications used for thromboprophylaxis. This reinforces the need to both harmonize and streamline clinical trials, while avoiding using the pandemic as an exception 7 to Good Clinical Practices. Despite considerable policy and financing attention on vaccine development, the world still faces shortfalls in manufacturing capacity and supply for vaccines that have received emergency use authorization. This reinforces the need for greater global collaboration at early stages (pre-approval) so that overall capacity (especially biologics capacity) is optimally allocated to the most efficacious and fieldadapted therapeutics (Table 1 ). It will also facilitate addressing proactiv
Keywords Extracted from PMC Text: NS-W Sarah Gilbert HL reports grants BL H. Co-Chair Bill Cidara Vice CEPI Bhavna Lall SS CB OE F2G COVID-19 Merck Vaccine Immunome SARS-CoV-2 vaccine BMGF Janssen Pharmaceuticals Heidi Larson, Denise Naniche, Gagandeep Kang, David Kaslow, Jerome Ansun BioPharma J. Peter Figueroa, Amplyx GK COVID-19 Vaccines T2 Sheahan SK biosciences Co-Chairs SaudiVax MEB PH ViiV Mayda Hassanain COVID-19 vaccines SS reports grants Shmuel Shoham Therapeutics Task Force GlaxoSmithKline Acidophil
Extracted PMC Text Content in Record: First 5000 Characters:CB, NS-W, SS and OE wrote the first draft of the manuscript. PH, MEB, and BL managed the process of review. All authors contributed equally and provided critical feedback, reference sources, and critical revisions for intellectual content and verified the information presented here. *Lancet Commission on COVID-19 Vaccines and Therapeutics Task Force: Peter Hotez (Co-Chair), Maria Elena Bottazzi (Co-Chair), Carolina Batista, Onder Ergonul, J. Peter Figueroa, Sarah Gilbert, Mayda Gursel, Mazen Hassanain, Gagandeep Kang, David Kaslow, Jerome H. Kim, Bhavna Lall (Assistant to Co-Chairs), Heidi Larson, Denise Naniche, Timothy Sheahan, Shmuel Shoham, Annelies Wilder-Smith, Samba O. Sow, Nathalie Strub-Wourgaft, Prashant Yadav. MEB and PH are developers of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E Ltd., a commercial vaccine manufacturer for scale up, production, testing and licensure. MG participates in one of eight SARS-CoV-2 vaccine development projects supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) since March 2020. SG is cofounder of Vaccitech and has a patent on ChAdOx1 nCoV-19 licensed to AstraZeneca. MH is Founder and Managing Director of SaudiVax. JPF and GK are members of the WHO SAGE Working Group on COVID-19 vaccines. GK is independent director of Hilleman Laboratories Private Limited and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). DK reports grants from Bill and Melinda Gates Foundation (BMGF) and grants from CEPI. JHK reports personal fees from SK biosciences. HL reports grants and honoraria from GlaxoSmithKline for training talks and from Merck as a member of the Merck Vaccine Confidence Advisory Board, outside the submitted work. TS reports grants from National Institute of Allergy and Infectious Disease and Fast Grants and research contracts from GlaxoSmithKline, and ViiV Healthcare. SS reports grants from Ansun BioPharma, Astellas Pharma, Cidara Therapeutics, F2G, Merck, T2 Biosystems, Shire Pharmaceuticals, Shionogi, and Gilead Sciences, outside the submitted work; and personal fees from Amplyx Pharmaceuticals, Acidophil, Janssen Pharmaceuticals, Reviral, Intermountain Healthcare, Karyopharm Therapeutics, Immunome, and Celltrion, outside the submitted work. All other authors declare no conflict of interests. The authors views and opinions in the Commentary do not necessarily represent the views, decisions, or policies of the institutions, universities, or health systems with which they are affiliated.
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