Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial

Abstract

Background The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. 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 by Euroimmun ELISA) 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 new 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 screening SARS-CoV-2 RT-PCR positivity. 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. 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) was similar for both groups. Conclusions Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma

“…One trial evaluated 168 adults across 19 sites in the United States who had close contact exposure to a person with confirmed COVID-19 in the previous 5 days and a negative SARS-CoV-2 polymerase chain reaction test within the 24 hours before transfusion ( Supplement Table 11 ) ( 58 ). Persons were randomly assigned to 1 unit of high-titer CCP ( n = 87) or standard plasma ( n = 81).…”

Early and out‐of‐hospital use of COVID‐19 convalescent plasma: An international assessment of utilization and feasibility

“…There were six completed randomized control trials on the use of CCP in an outpatient setting or emergency room setting [ 6 , 10 , 11 , 12 , 13 , 14 ] (Table 1 ). Three of the peer‐reviewed trials enrolled patients with confirmed SARS‐CoV‐2 infection to one unit of high‐titre CCP versus placebo [ 6 , 10 , 11 ].…”

“…There are six completed therapeutic trials: two showed clinical benefit‐ one in high‐risk participants who were <72 h from symptom onset [ 6 ]; and the largest outpatient trial (1181 participants) showed benefit in people treated within 8 days of symptom onset [ 12 ]. The other trials did not show benefit [ 10 , 11 , 13 , 14 ]. In C3PO [ 10 ], more participants in the CCP arm were admitted to the hospital directly from the emergency department, which meant they met the primary outcome during their initial visit to the emergency department.…”

“…In a post hoc sensitivity analysis that excluded patients admitted to the hospital during their index visit, the posterior probability of superiority of CCP was 93% in the intention-to-treat population. The Convalescent Plasma to Limit SARS-CoV-2 Associated Complications (CSSC-004) trial[12] randomized adult outpatients with COVID-19 within 9 days of symptom onset to receive high-tier CCP versus non-immune plasma, thus demonstrating significantly fewer cases of hospitalization (i.e., the primary endpoint) in those who received CCP as compared to controls (relative risk reduction, 54%).The CSSC-001[13] compared high-titre CCP versus non-immune plasma as post-exposure prophylaxis. Participants with close contact exposure to someone with confirmed COVID-19 were enrolled; all were negative for SARS-CoV-2 at the time of enrolment.…”

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials

“…In fact, as a cost-effective treatment, CCP might be more suitable for these countries where antiviral and monoclonal antibodies were not readily available ( 54 ). Seventhly, the efficiency of CCP on post-exposure protection ( 90 ) was not assessed in our studies since the unconfirmed COVID-19 patients were not included according to our exclusion criteria. Eighthly, we didn’t assess the proportion of patients with negative nucleic acid test, time to the negative nucleic acid test, the proportion of patients with detectable endogenous antibodies after receiving CCP as our results.…”