Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection

Shmuel Shoham, Evan M Bloch, Arturo Casadevall, Daniel Hanley, Bryan Lau, Kelly Gebo, Edward Cachay, Seble G Kassaye, James H Paxton, Jonathan Gerber, Adam C Levine, Judith Currier, Bela Patel, Elizabeth S Allen, Shweta Anjan, Lawrence Appel, Sheriza Baksh, Paul W Blair, Anthony Bowen, Patrick Broderick, Christopher A Caputo, Valerie Cluzet, Marie Elena Cordisco, Daniel Cruser, Stephan Ehrhardt, Donald Forthal, Yuriko Fukuta, Amy L Gawad, Thomas Gniadek, Jean Hammel, Moises A Huaman, Douglas A Jabs, Anne Jedlicka, Nicky Karlen, Sabra Klein, Oliver Laeyendecker, Karen Lane, Nichol McBee, Barry Meisenberg, Christian Merlo, Giselle Mosnaim, Han-Sol Park, Andrew Pekosz, Joann Petrini, William Rausch, David M Shade, Janna R Shapiro, J Robinson Singleton, Catherine Sutcliffe, David L Thomas, Anusha Yarava, Martin Zand, Jonathan M Zenilman, Aaron A R Tobian, David Sullivan, Shmuel Shoham, Evan M Bloch, Arturo Casadevall, Daniel Hanley, Bryan Lau, Kelly Gebo, Edward Cachay, Seble G Kassaye, James H Paxton, Jonathan Gerber, Adam C Levine, Judith Currier, Bela Patel, Elizabeth S Allen, Shweta Anjan, Lawrence Appel, Sheriza Baksh, Paul W Blair, Anthony Bowen, Patrick Broderick, Christopher A Caputo, Valerie Cluzet, Marie Elena Cordisco, Daniel Cruser, Stephan Ehrhardt, Donald Forthal, Yuriko Fukuta, Amy L Gawad, Thomas Gniadek, Jean Hammel, Moises A Huaman, Douglas A Jabs, Anne Jedlicka, Nicky Karlen, Sabra Klein, Oliver Laeyendecker, Karen Lane, Nichol McBee, Barry Meisenberg, Christian Merlo, Giselle Mosnaim, Han-Sol Park, Andrew Pekosz, Joann Petrini, William Rausch, David M Shade, Janna R Shapiro, J Robinson Singleton, Catherine Sutcliffe, David L Thomas, Anusha Yarava, Martin Zand, Jonathan M Zenilman, Aaron A R Tobian, David Sullivan

Abstract

Background: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection.

Results: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups.

Conclusion: In this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection.

Trial registration: Clinicaltrial.gov number NCT04323800 .

Figures

Figure 1:
Figure 1:
Consort Diagram: Ψ Intention to treat analysis, including all transfused individuals. Those lost to follow-up between transfusion to end of follow-up contributed to the time at risk. Individuals with positive RT-PCR on day of transfusion were removed from analysis. * One randomized participant was found ineligible after randomization.
Figure 2:
Figure 2:
a, b: Cumulative incidence of laboratory detected SARS-CoV-2 infection; c.d: difference in restricted mean infection free time (RMIFT) (> 0: increased expected days to infection for CCP); e, f: risk difference (lower panels,

Figure 3:

a, b: Cumulative incidence of…

Figure 3:

a, b: Cumulative incidence of COVID-19; c, d: difference in restricted mean infection…

Figure 3:
a, b: Cumulative incidence of COVID-19; c, d: difference in restricted mean infection free time (RMIFT) (> 0: increased expected days to infection for CCP); e, f: risk difference (
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Figure 3:
Figure 3:
a, b: Cumulative incidence of COVID-19; c, d: difference in restricted mean infection free time (RMIFT) (> 0: increased expected days to infection for CCP); e, f: risk difference (

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