High-Dose Convalescent Plasma for Treatment of Severe COVID-19

Abstract

Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.

COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes

“… Trials that were stopped too early to observe benefit or with inherent design flaws and/or were underpowered such that the likelihood of success was reduced (e.g., C3PO [ 27 ]). Trials in which CCP was used to treat a condition not amenable to antibody intervention, such as hypoxia that is caused by pulmonary inflammation (e.g., COP20 [ 111 ], RBR-7f4mt9f [ 112 ], or REMAP-CAP [ 35 ]). …”

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

“…Among all the included studies, 4 studies ( 24 , 28 , 34 , 48 ) were preprinted and 28 studies ( 16 – 18 , 25 – 27 , 29 – 33 , 35 – 47 , 49 – 52 ) were published in peer-reviewed journals. 10 studies ( 24 , 26 , 31 , 38 , 41 , 43 , 44 , 46 , 50 , 51 ) were double-blind RCTs with placebo and 22 studies ( 16 – 18 , 25 , 27 – 30 , 32 – 37 , 39 , 40 , 42 , 45 , 47 – 49 , 52 ) were designed as open-label trials. All trials included patients with confirmed Covid-19 except for the RECOVERY trial ( 35 ), which included both suspected and confirmed COVID-19 patients.…”

“…The assessments of risk of bias were shown in Figure 2 . 8 studies ( 26 , 35 , 38 , 41 , 43 , 44 , 46 , 50 ) were regarded as low risk of bias, and 16 studies ( 16 – 18 , 25 , 27 , 29 , 30 , 32 , 37 , 39 , 40 , 42 , 45 , 47 , 49 , 52 ) contained potential performance bias for the open-label design. 4 studies were considered as containing potential bias due to early termination ( 31 , 33 , 36 , 51 ).…”

“…Indeed, for patients at the end stage of COVID-19, the pathology of lung parenchyma was mainly characterized by inflammatory infiltration and fibrosis resulting from the unbalanced pro-inflammatory response and cytokine storm, while replication of SARS-COV-2 contributed less to the damage ( 79 , 80 ). The initial course of COVID-19 might be viewed as an optimal therapeutic window period for exogenous antibodies to maximize their neutralization effect ( 32 , 81 ). However, our study found that there was no significantly lower 28-d mortality either in patients within 7 days from symptoms onset or those with more than 7 days.…”

Outcomes of convalescent plasma with defined high- versus lower-neutralizing antibody titers against SARS-CoV-2 among hospitalized patients: CoronaVirus Inactivating Plasma (CoVIP), double-blind phase 2 study

“…4 Among 26 phase 2 or 3 CCP trials identified in PubMed between 2020-2022, 18 measured nAb on all units reported (N=2,692 CCP participants) whereas the other eight either did not perform an end-titer assay 20 , reported nAb titer in only a subset of units 19,21 , or did not report nAb titer 3,22-25 (N=7,079 CCP partcipants). Using in-study mortality as the most consistently reported primary or secondary outcome, aggregate risk ratios for death in CCP treated-participants versus no CCP comparator groups in trials reporting incomplete or undefined nAb titer (n=8), median nAb < 1:160 (n=7), 26,27,28,4,29,30,31 or nAb ≥ 1:160 (n=11) 2,4,5,32-39 were 0.99 (0.93-1.04), 1.04 (0.86-1.26), and 0.88 (0.73-1.05), respectively ( supplementary figure 2 ). The median nAb titer in four studies exceeded 1:320, but only one other study reported a median nAb >1:640 in a CCP intervention arm.…”