April 27, 2022

Dr Tedros Adhanom Ghebreyesus

Director

World Health Organization

Geneva, Switzerland

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.

Sincerely yours,

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

Other signatories

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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