Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

Abstract

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.

A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia

“…The pressing need for treatments for the COVID-19 pandemic obliged the medical community and authorities to embrace the use of convalescent plasma (CP) as a potentially effective and easily accessible form of passive immunotherapy. Despite the rationale for use, and experience in other viral epidemics (1,2), several controlled clinical trials and observational studies have provided inconclusive results regarding the beneficial effects of CP in patients hospitalized for COVID-19 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The evidence suggests that the potential beneficial effects of CP may be limited to the subgroup of non-critical patients who receive high titers of antibodies early in the course of the disease before developing their own humoral immune response (3)(4)(5)(6)(7)(8), or to immuno-compromised oncohematological patients who may fail to mount an effective immune response (9).…”

Comparing antiviral strategies against COVID-19 via multiscale within-host modelling

“…In this work, we take the impact of the immune response on infection dynamics into account to perform a more robust analysis of different treatment options. Regarding the CP therapy, several studies performed in various countries have shown that this treatment is effective against COVID-19 infections and its safety has been well established in a randomized clinical trial (RCT) on a large population [5,[10][11][12][13][14][15]. However, finding the optimal dose and time for CP therapy is still debated [5].…”

CONVALESCENT plasma for COVID‐19: A meta‐analysis of clinical trials and real‐world evidence

“…A total of 4728 records were identified from databases, websites and citation searching. There were 47 studies 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 fulfilled the inclusion criteria and were used for the systematic review and meta‐analysis (Figure 1 ). Of 47 included studies, 21 were clinical trials 16 , 17 , 18 ,…”

“…Of 47 included studies, 21 were clinical trials 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 60 , 61 , 62 and 26 were observational studies. 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 55 , 56 , 57 , 58 , 59 Among clinical trials, there were 18 studies published in peer‐reviewed journals 16 , 17 , 18 , 19 , 20 , 21 , …”

“…The current systemic review and meta‐analysis aimed to summarize the existing data on the efficacy of CP in COVID‐19 patients, which remains a challenge to explore treatment for SARS‐CoV‐2 pandemic to respond the increasing of the incidence of SARS‐CoV‐2 infection. According to the eligible criteria, 47 studies 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 were included and critically evaluated. Corresponding to the results of our systematic review and meta‐analysis, the CP may be effective in reducing the mortality of CP‐treated COVID‐19 patients compared with non‐CP‐treated COVID‐19 patients, especially in severe or critical patients and in Asia region.…”