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COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials
Levine AC, Fukuta Y, Huaman MA, Ou J, Meisenberg BR, Patel B, Paxton JH, Hanley DF, Rijnders BJ, Gharbharan A, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
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Abstract
BACKGROUND Outpatient monoclonal antibodies are no longer effective and antiviral treatments for COVID-19 disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma is promising, clinical trials among outpatients have shown mixed results. METHODS We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, World Health Organization, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS Five included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titers below the median titer. CONCLUSIONS Among outpatients with COVID-19, treatment with COVID-19 convalescent plasma reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.
PICO Summary
Population
Adult COVID-19 outpatients (5 studies, n= 2,620).
Intervention
Intravenous COVID-19 convalescent plasma (CCP) transfusion (n= 1,305).
Comparison
Non-convalescent plasma or normal saline (n= 1,315).
Outcome
The virus neutralizing antibody dilutional titre levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1,315 control patients were hospitalized, versus 111 (8.5%) of 1,305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95% CI: 1.3% - 6.0%) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titre with a 7.6% absolute risk reduction (95% CI: 4.0% - 11.1%) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titres below the median titre.
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Comparing the efficacy and safety of apheresis and whole blood-derived platelet transfusions: a systematic review
Heddle NM, Arnold DM, Boye D, Webert KE, Resz I, Dumont LJ
Transfusion. 2008;48((7):):1447-58.
Abstract
BACKGROUND A systematic review and meta-analysis was performed to determine if there were differences between apheresis platelet concentrates (APCs) or platelets (PLTs) derived from whole blood (WBD) for the outcomes acute reactions, alloimmunization, refractoriness, corrected count increment (CCI), radiolabeled recovery and survival, time to next transfusion, and bleeding. STUDY DESIGN AND METHODS We searched Medline, Embase, the Cochrane Registry of Controlled Trials, PapersFirst, ProceedingsFirst, and AABB and ASH abstracts for randomized controlled trials (RCTs) comparing APCs and WBD PLTs for clinical outcomes. Study selection, data extraction, and methodologic quality assessments were performed in duplicate. Results were pooled using meta-analytic methods. RESULTS Ten RCTs met the inclusion criteria. Acute reactions per patient were lower for APCs (relative risk [RR], 0.65; 95% CI, 0.44-0.98); however, when controlling for leukoreduction, there was no significant difference (leukoreduced [LR]-APCs vs. LR-WBDs; odds ratio, 1.78; 95% CI, 0.87-3.62). There was no difference between products when reaction frequencies were assessed per transfusion (RR, 0.65; 95% CI, 0.33-1.28). APCs were associated with significantly higher CCIs than WBD PLTs at both 1 hour (weighted mean difference [WMD], 2.49; 95% CI, 2.21-2.77) and 18 to 24 hours (WMD, 1.64; 95% CI, 0.60-2.67). No conclusions could be made for the outcomes of alloimmunization and refractoriness. No studies addressed outcomes of time to next transfusion or bleeding. CONCLUSIONS Owing to the small number of trials and lack of comparability of PLT products for leukoreduction, we were unable to draw definitive conclusions about the clinical benefits of APCs compared with WBD PLTs. Rigorous RCTs using clinically important end points are needed to settle this issue.
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A systematic review and meta-analysis of platelets prepared from apheresis versus whole blood
Heddle NM, Arnold DM, Dumont LJ, Boye D, Webert KE
Transfusion. 2007;47((Suppl 3):):192-3A.. Abstract No. SP442