Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19

Abstract

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.

Is SARS‐CoV‐2 viral clearance in nasopharyngeal swabs an appropriate surrogate marker for clinical efficacy of neutralising antibody‐based therapeutics?

“…This study showed that the time to negative PCR was 14 days in CCP‐treated patients versus 9.5 days in 59 historical controls 54 . Unfortunately, most PSM studies did not assess this parameter at all 55‐66 . Yoon et al 57 found a correlation between anti‐Spike IgG titre and PCR Ct in CCP recipients, but antibody levels were not measured in matched controls.…”

Convalescent Plasma—A Light at the End of the Tunnel: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“…We found an earlier administration of CPT is associated with better odds for favorable outcomes. Similarly, a number of recent studies 17 , 18 also echoed that while early application of CPT is beneficial in critically ill COVID-19 patients, late CPT is futile. However, another recent RCT reported no significant reduction of mortality rate (OR 3.04, 95% CI 0.54–17.2, p = 0.25), and the requirement for mechanical ventilation (OR 3.04, 95% CI 0.54–17.2, p = 0.25) is associated with early administration of CPT in comparison with the deferred patients.…”

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

“…Of interest, a retrospective PSM study from Providence did not show any benefit, but patients were treated at a median of 7 days after onset of symptoms (67). Another PSM study from Yale associated CCP with a 35% reduction in mortality (68). That study is notable in that it included patients on mechanical ventilation who would not normally be expected to benefit from CCP and the percentage of individuals receiving corticosteroids was very low since the study was conducted in the early days of the pandemic in the USA.…”