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Early Outpatient Treatment for Covid-19 with Convalescent Plasma

Sullivan et al., New England Journal of Medicine, doi:10.1056/NEJMoa2119657 (date from preprint), CSSC-004, NCT04373460
Dec 2021  
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Mortality 86% Improvement Relative Risk ICU admission 25% Hospitalization 54% Conv. Plasma  CSSC-004  LATE TREATMENT  DB RCT Is late treatment with convalescent plasma beneficial for COVID-19? Double-blind RCT 1,181 patients in the USA (June 2020 - October 2021) Lower hospitalization with convalescent plasma (p=0.0052) c19early.org Sullivan et al., New England J. Medicine, Dec 2021 Favorsconv. plasma Favorscontrol 0 0.5 1 1.5 2+
RCT 1,181 outpatients in the USA, mean 6 days from symptom onset, showing lower hospitalization with treatment.
risk of death, 85.7% lower, RR 0.14, p = 0.12, treatment 0 of 592 (0.0%), control 3 of 589 (0.5%), NNT 196, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 25.4% lower, RR 0.75, p = 0.73, treatment 3 of 592 (0.5%), control 4 of 589 (0.7%), NNT 580.
risk of hospitalization, 54.3% lower, RR 0.46, p = 0.005, treatment 17 of 592 (2.9%), control 37 of 589 (6.3%), NNT 29.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Sullivan et al., 21 Dec 2021, Double Blind Randomized Controlled Trial, USA, peer-reviewed, 58 authors, study period 3 June, 2020 - 1 October, 2021, average treatment delay 6.0 days, trial NCT04373460 (history) (CSSC-004).
This PaperConv. PlasmaAll
Early Outpatient Treatment for Covid-19 with Convalescent Plasma
David J Sullivan, Kelly A Gebo, Shmuel Shoham, Evan M Bloch, Bryan Lau, Aarthi G Shenoy, Giselle S Mosnaim, Thomas J Gniadek, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Emily S Spivak, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, Jonathan M Gerber, Joann R Petrini, Patrick B Broderick, William Rausch, Marie-Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Jay S Raval, Seble G Kassaye, E Colin Foster, Michael Roth, Christi E Marshall, Anusha Yarava, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Atika Singh, Daniel E Ford, Douglas A Jabs, Lawrence J Appel, David M Shade, Stephan Ehrhardt, Sheriza N Baksh, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, Arturo Casadevall, Aaron A R Tobian, Daniel F Hanley
New England Journal of Medicine, doi:10.1056/nejmoa2119657
BACKGROUND Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the controlplasma group) occurred in participants who were not hospitalized. CONCLUSIONS In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.
n engl j med nejm.org 11 Convalescent Plasma for Early SARS-CoV-2 Infection the Moriah Fund; Octapharma; the Healthnetwork Foundation; and the Shear Family Foundation. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the trial participants who generously gave of their time and donated biologic specimens. Appendix The authors' full names and academic degrees are as follows: David J. Sullivan, M.D., Kelly A. Gebo, M.D., M.P.H., Shmuel Shoham, M.D., Evan M. Bloch
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Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Jonathan M.', 'family': 'Gerber', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Joann R.', 'family': 'Petrini', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Patrick B.', 'family': 'Broderick', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'William', 'family': 'Rausch', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Marie-Elena', 'family': 'Cordisco', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Jean', 'family': 'Hammel', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Benjamin', 'family': 'Greenblatt', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Valerie C.', 'family': 'Cluzet', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Daniel', 'family': 'Cruser', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Kevin', 'family': 'Oei', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Matthew', 'family': 'Abinante', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Laura L.', 'family': 'Hammitt', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Catherine G.', 'family': 'Sutcliffe', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Donald N.', 'family': 'Forthal', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Martin S.', 'family': 'Zand', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Edward R.', 'family': 'Cachay', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Jay S.', 'family': 'Raval', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Seble G.', 'family': 'Kassaye', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'E. Colin', 'family': 'Foster', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Michael', 'family': 'Roth', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Christi E.', 'family': 'Marshall', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Anusha', 'family': 'Yarava', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Karen', 'family': 'Lane', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Nichol A.', 'family': 'McBee', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Amy L.', 'family': 'Gawad', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Nicky', 'family': 'Karlen', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Atika', 'family': 'Singh', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Daniel E.', 'family': 'Ford', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Douglas A.', 'family': 'Jabs', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'ORCID': 'http://orcid.org/0000-0002-0673-6823', 'authenticated-orcid': False, 'given': 'Lawrence J.', 'family': 'Appel', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'David M.', 'family': 'Shade', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Stephan', 'family': 'Ehrhardt', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Sheriza N.', 'family': 'Baksh', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Oliver', 'family': 'Laeyendecker', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'ORCID': 'http://orcid.org/0000-0003-3248-1761', 'authenticated-orcid': False, 'given': 'Andrew', 'family': 'Pekosz', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Sabra L.', 'family': 'Klein', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9402-9167', 'authenticated-orcid': False, 'given': 'Arturo', 'family': 'Casadevall', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Aaron A.R.', 'family': 'Tobian', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}, { 'given': 'Daniel F.', 'family': 'Hanley', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Medicine, Division of Infectious Diseases ' '(K.A.G., S.S.), the Department of Pathology (E.M.B., C.E.M., ' 'A.A.R.T.), the Department of Neurology, Brain Injury Outcomes ' 'Division (A.Y., K.L., N.A.M., A.L.G., N.K., D.F.H.), the ' 'Department of Ophthalmology (D.A.J.), the Welch Center for ' 'Prevention, Epidemiology and Clinical Research (L.J.A.), and the ' 'Institute for Clinical and Translational Research (D.E.F.), ' 'Johns Hopkins School of Medicine, and the Departments of ' 'Molecular Microbiology...'}]}], 'member': '150', 'published-online': {'date-parts': [[2022, 3, 30]]}, 'container-title': ['New England Journal of Medicine'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://www.nejm.org/doi/pdf/10.1056/NEJMoa2119657', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 3, 30]], 'date-time': '2022-03-30T21:01:24Z', 'timestamp': 1648674084000}, 'score': 1, 'resource': {'primary': {'URL': 'http://www.nejm.org/doi/10.1056/NEJMoa2119657'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 3, 30]]}, 'references-count': 25, 'alternative-id': ['10.1056/NEJMoa2119657'], 'URL': 'http://dx.doi.org/10.1056/nejmoa2119657', 'relation': {}, 'ISSN': ['0028-4793', '1533-4406'], 'issn-type': [{'value': '0028-4793', 'type': 'print'}, {'value': '1533-4406', 'type': 'electronic'}], 'subject': ['General Medicine'], 'published': {'date-parts': [[2022, 3, 30]]}}
Late treatment
is less effective
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