Introduction
Early reports from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic suggested that children were less severely affected by coronavirus disease (COVID-19) compared to older adults.1-3 Nevertheless, some children with COVID-19 are critically ill.4,5 Currently, no therapies have been proven effective in the treatment of COVID-19 in children.
Convalescent plasma (CP), derived from patients that have recovered from SARS-CoV-2 can be infused into currently ill patients. The proposed mechanism of action is via neutralizing antibodies binding to virus, rendering it inert.6 Specific to SARS-CoV-2, antibodies against the receptor binding domain (RBD) have been identified as surrogates for neutralization.7-11 CP also contains antibodies against the immunogenic nucleocapsid (N) protein, which are non-neutralizing and present in both actively infected and recovered patients.7 The protective function of N antibodies remains unclear.7,12Antibodies against the full-length SARS-CoV-2 Spike (S) protein include both non-neutralizing antibodies and neutralizing antibodies.13
Initial series of CP in adults with COVID-19 demonstrated potential benefits without apparent side effects.14-16 In a recent clinical trial of adults with COVID-19, there was a non-statistically significant trend towards clinical improvement in CP-treated patients versus controls, without improvement in time to discharge or mortality.17 This trial was halted early due to poor accrual.17 To date, there have been no reports on the use of CP in children.
CP infusion is associated with the side effects of any blood product: allergic reaction, transfusion-associated circulatory overload (TACO), and infection with blood borne pathogens. There is a theoretical risk that infusion of donor antibodies may impede the recipient’s endogenous production of antibodies, and of antibody-dependent enhancement (ADE), where antibodies developed during a previous infection cause a worsened clinical response with subsequent infection. ADE has been described in Dengue fever, and in pre-clinical models of other coronaviruses.18-20 ADE has not been reported in adult patients receiving CP for SARS-CoV2.6,17
We present the first report of pediatric patients receiving CP for life-threatening COVID-19 associated respiratory disease with correlative measurements of the associated pre- and post- transfusion antibody response.