Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19

Abstract

Background: COVID-19 convalescent plasma (CCP) has been considered a treatment option in COVID-19. This trial assessed the efficacy of neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.Methods: Patients (n=105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. Primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. Results:The primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (p=0.27). Median time to discharge from hospital was 31 days in the CCP and 51 days in the control group (p=0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies the primary outcome occurred in 56.0% (versus 32.1%), with significantly shorter intervals to clinical improvement (20 versus 66 days)(p<0.05), and to hospital discharge (21 versus 51 days, p=0.03) and better survival (day-60 probability of survival 91.6% versus 68.1%; p=0.02) compared to the control group. Conclusion:CCP added to standard treatment was not associated with significant improvement in the primary and secondary outcomes. A pre-defined subgroup analysis showed a significant benefit for CCP among those who received a larger amount of neutralizing antibodies.

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia

“…In the TSUNAMI trial, 30-day mortality was 6.1% for the CP group and 7.9% for the control group. Published 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 and unpublished RCTs 10 , 11 , 12 have failed to demonstrate any benefit of CP on mortality with the exception of the study by O’Donnell et al 14 that found a significant reduction of 28-day mortality in patients receiving CP. In the RECOVERY trial, 4 the mortality rate was 24.1% and 24.4% in the CP group and control group, respectively.…”

“…These striking differences are difficult to explain and are probably multifactorial: difference in the population's median age, difference in the risk factors for progression to severe COVID-19, time lapse between disease onset and CP transfusion, and differences in comprehensive patient management. It has been suggested that the benefits of CP may depend on the plasma NAb titer 9,13 and that using CP with a low titer could explain negative results. To our knowledge, TSUNAMI was among the first and few RCTs using qualified CP 25 The presence of anti-SARS-CoV-2 IgG antibodies in recipients before receiving CP has also been cited as a possible reason for lack of effect of CP.…”

“…Convalescent plasma (CP) from individuals recovered from SARS-CoV-2 infection has been proposed as therapy for patients with COVID-19, but the clinical evidence of its benefit is limited. Randomized clinical trials (RCTs) already published 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 or available as preprint versions 10 , 11 , 12 have not shown a clear benefit of CP in reducing the risk of disease progression or death. However, a relationship between neutralizing antibody (NAb) titer and a more favorable clinical outcome have been suggested, 9 , 13 and CP was associated with a decreased 28-day mortality rate when high titer plasma was used 14 or when CP was administered early in the course of the disease.…”

“…Randomized clinical trials (RCTs) already published 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 or available as preprint versions 10 , 11 , 12 have not shown a clear benefit of CP in reducing the risk of disease progression or death. However, a relationship between neutralizing antibody (NAb) titer and a more favorable clinical outcome have been suggested, 9 , 13 and CP was associated with a decreased 28-day mortality rate when high titer plasma was used 14 or when CP was administered early in the course of the disease. 15 Data from available RCTs have several limitations, including the administration of plasma with low NAb titer, the use of suboptimal surrogate serological tests to determine NAb titer, and most importantly, the delayed administration of CP from the onset of COVID-19 symptoms.…”

Convalescent plasma may not be an effective treatment for severe and critically ill covid-19 patients: A Systematic Review & Meta-Analysis of Randomized Controlled Trials

“…After thoroughly reading the title and the abstract, unrelated literature on the convalescent plasma treatment of COVID-19 was excluded. After scrutinizing the studies based on the inclusion & exclusion criteria, a total of 14 randomized controlled trials and 4543 patients were included in the meta-analysis [ 2 , 7 , 10 , 11 , 12 , 13 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ] ( Fig. 1 ).…”