Effects of Potent Neutralizing Antibodies from Convalescent Plasma in Patients Hospitalized for Severe SARS-CoV-2 Infection.

Abstract

Convalescent plasma could be an inexpensive and widely available treatment for COVID-19 patients but reports on effectiveness are inconclusive. We collected convalescent plasma from donors with high titers of neutralizing anti-SARS-CoV-2 antibodies effectively blocking SARS-CoV-2 infection in vitro. In a randomized clinical trial of 86 COVID-19 patients, no overall clinical benefit of 300 mL convalescent plasma was found in patients hospitalized for COVID-19 in the Netherlands. Using a comprehensive translational approach, we unraveled the virological and immunological responses following plasma treatment which helps to understand which COVID-19 patients may benefit from this therapy and should be the focus of future studies. Convalescent plasma treatment in this patient group did not improve survival, had no effect on the clinical course of disease, nor did plasma enhance viral clearance in the respiratory tract, influence anti-SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. The vast majority of patients already had potent neutralizing anti-SARS-CoV-2 antibodies at hospital admission and at comparable titers as the carefully selected plasma donors. Together, these data indicate that the variable effectivity observed in trials on convalescent plasma for COVID-19 may be explained by the timing of treatment and varying levels of preexisting anti-SARS-CoV-2 immunity in patients. It also substantiates that convalescent plasma should be studied as early as possible in the disease course or at least preceding the start of an autologous humoral response. Trial registration: Clinicaltrials.gov: NCT04342182

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

“…However, in the CAPSID trial, the proportion of patients with life-threatening disease, i.e. requiring invasive ventilation or ECMO, was higher than in most other trials (6)(7)(8)(9)(10)(11)(12)(13)16). This trial included a larger proportion of patients with poor prognosis -based on proportion of patients with invasive ventilation, high inflammation markers and comorbidities which are associated with poor outcome (28).…”

“…Other trials which also included hospitalized patients requiring respiratory support at least in a proportion of patients also did not report significant differences in clinical improvement or all-cause mortality (6)(7)(8)(9)(10)(11)(12)(13)16). However, in the CAPSID trial, the proportion of patients with life-threatening disease, i.e.…”

“…It has been broadly used in an Expanded Access Program (3) in the US and preliminary reports on signals of efficacy and safety led to an Emergency Use Authorization in the US in August 2020 (4,5). A large number of clinical trials on CCP have been initiated since the start of the pandemic (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Clinical trial outcomes assessing efficacy have been mixed.…”

“…In contrast, another meta-analysis concluded that patients with COVID-19 transfused with CCP exhibited a lower mortality rate compared with patients receiving standard treatments and it showed that early transfusion of higher titer plasma is associated with lower patient mortality (20). The volume of CCP transfused was low in some of the trials (6,7,9,10,12,14) and the content of antibodies in CCP units was poorly characterized or only measured post-hoc in some of the trials. Therefore, it is important to gather data from further controlled clinical trials using well defined CCP.…”

Perspective on therapeutic and diagnostic potential of camel nanobodies for coronavirus disease-19 (COVID-19)

“…Therapeutic trials based on the administration of plasma with high antibody titers may be more beneficial than low-titer plasma in non-incubated patients, particularly when administered within 72 h of COVID-19 diagnosis. However, the use of convalescent plasma did not always lead to the recovery (Gharbharan et al 2020 ).…”