Use of convalescent serum reduces severity of COVID-19 in nonhuman primates

Abstract

Passive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against SARS-CoV-2 is currently being used to treat COVID-19 patients where clinical efficacy trials are ongoing. Here, we assess therapeutic passive transfer in groups of SARS-CoV-2-infected African green monkeys with convalescent sera containing either high or low anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and pathology are minimal between monkeys that receive the lower titer convalescent sera and untreated controls. However, lower levels of SARS-CoV-2 in respiratory compartments, reduced severity of virus-associated lung pathology, and reductions in coagulopathy and inflammatory processes are observed in monkeys that receive high titer sera versus untreated controls. Our data indicate convalescent plasma therapy in humans may be an effective strategy provided donor sera contain high anti-SARS-CoV-2 neutralizing titers given in early stages of disease.

SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma

“…In fact, a recent clinical trial reports that CP pools with higher neutralizing antibody titers are associated with increased clinical benefit ( 13 ). This finding is consistent with a recent report that African green monkeys (AGM) transfused 10 h postinfection with a pool of high-titer (50% plaque reduction/neutralization titer [PRNT 50 ] of 2,048) convalescent AGM plasma had lower viral loads in the respiratory tract, reduced lung pathology and normalization of the prolonged coagulation times, elevated fibrinogen, thrombocytopenia, and hypercytokinemia seen in untreated animals ( 26 ). Our results with moderate-titer human CP in rhesus macaques are largely consistent with a report that low-titer AGM CP given 10 h postinfection had little effect on virus replication in AGMs ( 26 ).…”

Antibody Responses in COVID-19: A Review

“…In fact, only hospitalized patients who were not receiving mechanical ventilation and received plasma transfusions with higher antibody titers appear to have benefit in clinical outcomes (50). Also, in an animal model with green monkeys, it was noted that those who received higher antibody titers had lower SARS-CoV-2 levels in the respiratory compartments, less severity of virus-related lung pathology, reduction in coagulopathy and inflammatory processes (58).…”

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

“…For example, convalescent serum from Syrian hamsters elicited an antiviral effect when administered to infected animals ( 37 ). Similarly, among SARS-CoV-2-infected green monkeys, transfusion of convalescent plasma from the same species reduced lung pathology, viral shedding, and inflammation ( 38 ). In addition, administration of human convalescent plasma protected mice expressing the human ACE2 receptor from SARS-CoV-2 infection ( 39 ).…”