Open letter to WHO for revisions to CCP recommendations
April 27, 2022
Dr Tedros Adhanom Ghebreyesus
World Health Organization
Dear Dr Tedros Adhanom Ghebreyesus,
We write to request that the WHO update its COVID-19 convalescent plasma (CCP) recommendations, last issued on December 7, 2021, that recommended against its use in early disease stages. A prior statement by the U.S. COVID-19 Convalescent Plasma Project leadership argued that this recommendation was misguided based on the knowledge available at the time (1). WHO recommendations are based largely on the analysis of randomized controlled trials published early in the pandemic that focused on hospitalized patients with late-stage disease. As we have noted in a comprehensive analysis (2), the majority of these RCTs used CCP too late in the course of disease to affect outcome. There are now algorithms that identify patients likely to benefit from CCP (3).
Since December 2021, additional powerful evidence has been published showing that CCP is effective when used early in the course of disease (4). Both the Infectious Disease Society of America and the Association for the Advancement of Blood & Biotherapies (AABB) now recommend the early use of CCP in certain COVID-19 patient populations. The totality of current evidence indicates that CCP administration with units having a high concentration of antibodies to SARS-CoV-2 reduces the likelihood of hospitalization and reduces mortality if administered to out-patients early in the course of disease.
The efficacy of CCP is comparable, or even superior, to that seen in registration trials for monoclonal antibodies and small-chemical antivirals when infused within the first five days of symptoms. CCP reduces the rate of hospitalization by about 80% in immunocompetent outpatients at risk of disease progression (4). Furthermore, CCP is finding major use in immunosuppressed patients who often cannot make adequate antibody responses following vaccination or after infection (5-7).
While antiviral therapies have been available in affluent countries, low- and middle-income countries often lack the financial resources to order expensive monoclonal antibodies and antiviral drugs to treat COVID-19. However, these countries do have the capacity to produce CCP. Manufacturing CCP is nowadays easier than ever thanks to the availability of vaccinated convalescents among regular donors: in them, vaccination boosts neutralizing antibody titers and expands their cross-reactivity against multiple variants of concern. The safety of CCP has been confirmed in hundreds of thousands of patients (8).
It is important also to note that only a few monoclonal antibodies retain their effectiveness against newly mutated strains, such as the currently circulating variant of concern, BA.2. We are confident that if you review the information now publicly available you will amend WHO recommendations to support CCP use in certain patient populations, as previously done by both the IDSA and AABB. We believe this step should be taken URGENTLY to encourage countries to make CCP available to their citizens, a step with the potential to save many lives.
The US Convalescent Plasma Project Leadership team (ccpp19.org)
Arturo Casadevall MD, PhD, Johns Hopkins School of Public Health, USA
Brenda Grossman MD, Washington University, USA
Jeffrey Henderson MD, PhD. Washington University, USA
Michael Joyner MD, Mayo Clinic, USA
Nigel Paneth MD, Michigan State University, USA
Liise-anne Pirofski MD, Albert Einstein College of Medicine, USA
Shmuel Shoham MD, Johns Hopkins School of Medicine, USA
Jennifer Alexander-Brett, MD, PhD, Washington University, USA
Joanna Paes Barreto Bokel, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Therese Youssef Andraos MD, Montefiore Medical Center, USA
Elliot Antman MD, Brigham and Women’s Hospital, Harvard Medical School, USA
Peter Agre MD, Nobelist, Johns Hopkins University, Baltimore, USA
Nimer Assy, Galile medical center, bar Ilan university, Nahariya. Israel
Katherine Bar, University of Pennsylvania, USA
Rachel Bartash MD, Albert Einstein College of Medicine and Montefiore Medical Century, USA
Massimiliano Beccaria, Carlo Poma Hospital, Mantua, Italy
Giovanni Belcari, Azienda USL Toscana Nord-Ovest, Portoferraio, Italy
Thierry Burnouf, Taipei University, Taiwan
Prasun Bhattacharya MD, Medical College, Kolkata, India
Edward Cachay, M.D., University of San Diego Health, USA
Sandra Wagner Cardoso, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brasil
Laura Cheney MD, Albert Einstein College of Medicine and Montefiore Medical Center, USA
Mario Corbellino, Ospedale Luigi Sacco, Milan, Italy
Marie Elena Cordisco, M.A., Nuvance Health, USA
Marilou Corpuz MD, Albert Einstein College of Medicine and Montefiore Medical Center, USA
Peter Crawford, MD, PhD, University of Minnesota, USA
Judith Currier, M.D., M.Sc., UCLA Health USA
Maria Pia Diniz, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
David Esses MD, Montefiore Medical Center, USA
Todd Fehniger, MD, PhD, Washington University, USA
Yuriko Fukuta, MD, Ph.D., Baylor College of Medicine, USA
Daniele Focosi MD, PhD, North-Western Tuscany Blood Bank, Italy
Massimo Franchini, Carlo Poma Hospital, Mantua, Italy
Neil Gaffin MD, Valley Health System, USA
David Gachoud, MD, University Hospital of Lausanne, Switzerland.
Dipyaman Ganguly MBBS PhD PhD, CSIR-Indian Institute of Chemical Biology, Kolkata, India
Amy Gawad, M.P.H, Johns Hopkins School of Medicine, USA
Kelly Gebo MD, Johns Hopkins University, Baltimore, USA
Inessa Gendlina MD, PhD, Albert Einstein College of Medicine and Montefiore Medical Center, USA
Claudia Glingani, Carlo Poma Hospital, Mantua, Italy
Robert Goldstein MD, Montefiore Health System, USA
Rada Grabovic, President of Macedonian Society for Transfusion Medicine, Skopje, Macedonia
Elizabeth Griffiths, MD, Roswell Park Comprehensive Cancer Institute, USA
Beatriz Grinsztejn MD, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Esau Custodio João, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Balazs Halmos MD, Montefiore Medical Center, USA
Daniel Hanley, M.D., Johns Hopkins School of Medicine
William Hartman, MD, University of Wisconsin, USA
Sonya Heath, M.D., University of Alabama at Birmingham, USA
Vagish Hemmige MD, Albert Einstein College of Medicine and Montefiore Medical Center, USA
Hitoshi Honda, MD, PhD, Tokyo Metropolitan Tama General Medical Center, Tokyo, Japan
Judith S. Hochman, MD, NYU Grossman School of Medicine, New York, USA
Peter Hotez MD, PhD, Baylor College of Medicine, USA
Moises Huaman, M.D., M.Sc. , University of Cincinnati College of Medicine, USA
Thomas Hueso MD, Department of Hematology, Gustave Roussy, Villejuif, France
Noreen A Hynes, MD, MPH, Johns Hopkins University, Baltimore, USA
Clara Hwang, MD, Henry Ford Cancer Institute, USA
Esau Custodio Joao, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Sabra Klein, Ph.D., Johns Hopkins University, USA
Vadim S Koshkin, MD, University of California San Francisco, USA
Camille Nelson Kotton MD, Harvard Medical School, Boston, USA
Karine Lacombe MD, Sorbonne Université, Inserm UMR-S1136, IPLESP, Paris, France
Adam C. Levine, MD, MPH, FACEP, Brown University, Providence, USA
W. Ian Lipkin, MD, Columbia University, New York, USA
Barry Meisenberg, M.D., Johns Hopkins University, USA
Daniela Palheiro Mendes de Almeida, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Dok Mo MD, Bandung, Indonesia
Giselle Mosnaim, M.D., M.S., NorthShore University Health System, USA
James Musser MD, PhD, Houston Methodist Hospital, Texas, USA
Andre Nicola, Faculty of Medicine, University of Brasília, Brazil
Priya Nori MD, Albert Einstein College of Medicine and Montefiore Medical Center. USA
Nguyet Nguyen MD, Washington University, USA
Max O'Donnell MD, MPH, Columbia University, USA
Mila Ortigoza MD, PhD, NYU Langone, USA
James H. Paxton, M.D., Wayne State University, USA
Eva Petkova PhD, NYU Langone, USA
Jose Henrique Pilotto, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Jimena Prieto MD, Programa Nacional de Trasplante Hepático, Uruguay
Yoram Puius MD, Albert Einstein College of Medicine and Montefiore Medical Center, USA
Jay Raval, M.D., University of New Mexico Health Sciences, USA.
Yogiraj Ray MD, Institute of Postgraduate Medical Education and Research, Kolkata, India
Nathalie Rufer, MD, PhD, University Hospital of Lausanne, Lausanne Switzerland
Cristina Sanz MD, Director of the Blood Bank and Transfusion Service, BST-Clínic, Barcelona, Spain
Martin R. Salazar MD, Facultad de Ciencias Médicas, UNLP, Argentina
Shiv. K. Sarin, MD, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
Michele Schiavulli, Azienda Ospedaliera di Rilievo Nazionale Santorini-Pausilipon, Naples, Italy
Dimpy P. Shah, MD, PhD, University of Texas, San Antonio, USA
Pankil Shah, MD, PhD, University of Texas, San Antonio, USA
Hubert Schrezenmeier, German Red Cross Blood Transfusion Service, University of Ulm, Germany.
Al Sommer MD, Johns Hopkins University, USA
David Sullivan MD, Johns Hopkins University, Baltimore, USA
Emily Sydnor, M.D. M.H.S., University of Utah Health, USA
Michael Thompson, MD, PhD, VP of Clinical Partnerships, Tempus Labs, USA
Sedulla Useini MD, Institute for Transfusion Medicine of RNM, Skopje, North Macedonia
Jeremy L. Warner MD, MS, Vanderbilt University, USA
Aaron Tobian, M.D, Johns Hopkins University, USA
Andrea Troxel PhD, NYU Langone, USA
Amit Verma MD, Albert Einstein College of Medicine, USA
Alexandre Vizzoni, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Valdilea Gonçalves Veloso, Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Brazil
Hyun ah Yoon MD, Albert Einstein College of Medicine and Montefiore Medical Center, USA
Peter Paul Yu MD FACP FASCO, Hartford Healthcare Cancer Institute, USA
Martin S. Zand, MD, PhD, University of Rochester Medical Center
Matteo Zani, Carlo Poma Hospital, Mantua, Italy
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