Treating COVID-19 with Potent Neutralizing Antibodies

Convalescent plasma as a potential treatment for COVID-19 has been discussed and explored since the start of the pandemic. The plasma contains therapeutic antibodies that could be passively transferred to a recipient with the virus and could be an inexpensive and widely available therapy. However, so far any reports on its effectiveness have been inconclusive.

A recent study conducted by investigators sought to further explore this potentially important topic. The data was presented during the Conference on Retroviruses and Opportunistic Infections (CROI) 2021 virtual sessions.

The investigators behind the study collected convalescent plasma with high titers of neutralizing anti-SARS-CoV-2 antibodies and assessed their clinical and viro-immunological responses in patients with a severe infection of COVID-19.

The study, a multicenter open-label randomized clinical trial, included 86 participants from 14 secondary and academic hospitals in the Netherlands who were admitted to a hospital with COVID-19 and were not on mechanical ventilation for >96 hours. The participants were 72% male, had a median age of 63 years and had a median 10 days of symptoms. They were randomized to convalescent plasma or standard of care.

The convalescent plasma was selected from donors based on a SARS-CoV-2 plaque reduction neutralization test (PRNT50) result of ≥1:80.

Findings from the study showed no significant difference in mortality between arms after adjustment at day 60 of using 300mL of convalescent plasma. Also comparable were the World Health Organizations (WHO) COVID-19 disease severity scores at day 15 and time to discharge. Additionally, no effect was observed with convalescent plasma on viral clearance in the respiratory tract, anti-SARS-CoV-2 antibody development or changes in serum pro-inflammatory cytokine levels.

The study was interrupted due to study futility based on a recommendation from the Data and Safety Monitoring Board (DSMB).

“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,” the authors wrote. “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.”