Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
et al., Nature Communications, doi:10.1038/s41467-021-23469-2, NCT04342182 (history)
, Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe.., Nature Communications, doi:10.1038/s41467-021-23469-2, NCT04342182
RCT 86 hospitalized patients, 43 treated with convalescent plasma, showing no significant differences with treatment. Authors conclude that the most likely explanation was already high antibody titers on the day of inclusion, and they recommend treating patients early. NCT04342182 (history).
|
risk of death, 3.8% lower, RR 0.96, p = 0.95, treatment 6 of 43 (14.0%), control 11 of 43 (25.6%), NNT 8.6, adjusted per study, odds ratio converted to relative risk, multivariable logistic regression, primary outcome.
|
|
time to discharge, 11.7% lower, relative time 0.88, p = 0.68, treatment 43, control 43, adjusted per study, multivariable Fine and Gray regression.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Gharbharan et al., 27 May 2020, Randomized Controlled Trial, Netherlands, peer-reviewed, 32 authors, average treatment delay 10.0 days, trial NCT04342182 (history).
Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
Nature Communications, doi:10.1038/s41467-021-23469-2
In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.
Author contributions
Competing interests The
Additional information
Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41467-021-23469-2. Correspondence and requests for materials should be addressed to C.R. Reprints and permission information is available at http://www.nature.com/reprints Peer review Information Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Agarwal, Convalescent plasma in the management of moderate covidin adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial), BMJ
Arabi, Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia, Emerg. Infect. Dis
Beigel, Remdesivir for the treatment of Covid-19 -final report, N. Engl. J. Med, doi:10.1056/NEJMoa2007764
Bonanad, The effect of age on mortality in patients with COVID-19: a meta-analysis with 611,583 subjects, J. Am. Med. Dir. Assoc
Both, Passive immunity in the prevention of rabies, Lancet Infect. Dis
Brouwer, Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability, Science
Cap, REMAP
Carrillo, Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2020.10.108
Cheng, Use of convalescent plasma therapy in SARS patients in Hong Kong, Eur. J. Clin. Microbiol. Infect. Dis
Devasenapathy, Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis, Cmaj
Duan, Effectiveness of convalescent plasma therapy in severe COVID-19 patients, Proc. Natl Acad. Sci
Fine, Gray, A proportional hazards model for the subdistribution of a competing risk, JASA
Geurtsvankessel, An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment, Nat Comms
Geurtsvankessel, An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment, Nat. Commun
Haagmans, SARS-CoV-2 neutralizing human antibodies protect against lower respiratory tract disease in a hamster model, doi:10.1101/2020.08.24.264630
Horby, Dexamethasone in hospitalized patients with Covid-19 -preliminary report, N. Engl. J. Med
Hung, Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection, Chest
Jiang, Zhang, Yang, Hotez, Du, Neutralizing antibodies for the treatment of COVID-19, Nat. Biomed. Eng
Jin, Gender differences in patients with COVID-19: focus on severity and mortality, Front. Public Health
Joyner, Convalescent plasma antibody levels and the risk of death from Covid-19, N Engl J Med
Joyner, Early safety indicators of COVID-19 convalescent plasma in 5,000 patients, J. Clin. Invest
Joyner, Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience, doi:10.1101/2020.08.12.20169359v1
Klasse, Neutralization of virus infectivity by antibodies: old problems in new perspectives, Adv. Biol
Li, Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial, JAMA
Liu, Convalescent plasma treatment of severe COVID-19: a matched control study, Nat Med
Long, Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections, Nat. Med, doi:10.1038/s41591-020-0965-6
Mair-Jenkins, The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis, J. Infect. Dis
Okba, Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease 2019 patients, Emerg. Infect. Dis
Orlando, Prevention of hepatitis B virus infection: from the past to the future, Eur. J. Clin. Microbiol. Infect. Dis
Pan, Repurposed antiviral drugs for COVID-19 -interim WHO SOLIDARITY trial results. WHO Solidarity Trial Consortium, N Engl J Med
Pau, Convalescent plasma for the treatment of COVID-19: perspectives of the National Institutes of Health COVID-19 treatment guidelines panel, Ann. Intern. Med
Perotti, Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter interventional trial, Haematologica
Petkova, Antman, Troxel, Pooling data from individual clinical trials in the COVID-19 era, JAMA, doi:10.1001/jama.2020.13042
Piechotta, Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review, Cochrane Database Syst. Rev
Safety, tolerability, and efficacy of anti-spike (S) SARS-CoV-2 monoclonal antibodies for the treatment of ambulatory adult patients with COVID-19
Shen, Treatment of 5 critically ill patients with COVID-19 with convalescent plasma, JAMA
Van Kampen, Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants, Nat Comms
Wang, A human monoclonal antibody blocking SARS-CoV-2 infection, Nat. Commun
Wang, C-reactive protein level may predict the risk of COVID-19 aggravation, Open Forum Infect. Dis
Wang, Neutralizing antibodies responses to SARS-CoV-2 in COVID-19 inpatients and convalescent patients, Clin. Infect. Dis
Wölfel, Virological assessment of hospitalized patients with COVID-2019, Nature
Xu, Mao, Chen, Risk factors for 2019 novel coronavirus disease (COVID-19) patients progressing to critical illness: a systematic review and meta-analysis, Aging
Zhang, Treatment with convalescent plasma for critically ill patients with severe acute respiratory syndrome coronavirus 2 infection, Chest
Zhao, Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a systemic review and meta-analysis, Int. J. Infect. Dis
Zhou, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet
Late treatment
is less effective
is less effective
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.