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Enrichment of Astrocyte-Derived Extracellular Vesicles from Human Plasma
Published on: August 3, 2022
Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19
Neima Briggs1, Michael V Gormally1, Fangyong Li2
1Department of Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.
Insights
Early administration of COVID-19 convalescent plasma (CCP) significantly reduced mortality and improved recovery in moderate-to-severe COVID-19 patients. Late CCP treatment showed no significant clinical benefits, highlighting the critical role of timing in therapeutic efficacy.
Area of Science:
- Infectious Diseases
- Immunology
- Critical Care Medicine
Background:
- Limited therapeutic options for COVID-19 necessitate exploring novel treatments.
- COVID-19 convalescent plasma (CCP) is a potential therapy, but data for severe cases is scarce.
Purpose of the Study:
- To evaluate the outcomes of CCP administration in patients with moderate-to-severe COVID-19.
- To investigate the impact of early versus late CCP administration on patient recovery and mortality.
Main Methods:
- Propensity score-matched analysis of COVID-19 patients receiving CCP versus an unexposed cohort.
- Primary endpoint: in-hospital mortality. Secondary endpoints: days alive and ventilator-free, hospital stay length, WHO score changes.
- Analysis stratified by early (≤6 days) and late (>6 days) CCP administration.
Main Results:
- Early CCP recipients showed significantly lower 14-day and 30-day mortality (15% vs 23% and 38% vs 49%, respectively).
- Early CCP was associated with a nearly 50% reduction in in-hospital mortality (HR 0.52) and improved days alive and ventilator-free.
- Late CCP administration did not demonstrate significant clinical differences compared to the unexposed cohort.
Conclusions:
- Early administration of CCP is associated with improved outcomes in moderate-to-severe COVID-19.
- The timing of CCP administration is critical, with early treatment showing benefits not observed with late treatment.
- Further trials should focus on the optimal timing for CCP interventions.
Background:
Limited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease.
Research Question:
What are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection?
Study Design And Methods:
We conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching.
Results:
Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28-0.96]; P = 0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P = 0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to -0.4]; P = 0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P = 0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients.
Interpretation:
Early administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.
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