SARS-CoV-2 RNA from Pre-Symptomatic Donor Plasma Not Infectious in Models

New findings from investigators at American Red Cross, Bloodworks Northwest, New York Blood Center and Vitalant confirmed that plasma collected from donors with pre-symptomatic COVID-19 continues to be highly unlikely to transmit SARS CoV-2 infection. Investigators published their findings, conducted as part of the REDS-IV-P program, in the Journal of Clinical Investigation.

Although there has been no evidence of transfusion-transmitted SARS-CoV-2 resulting in COVID-19, investigators sought to assess to what degree SARS-CoV-2 could potentially find its way into the blood supply from pre-symptomatic donors, and what if any impact it could have on patient care. To do so, they tested 2,250 quarantined plasma samples from blood donors who reported possible COVID-19 infection within 14 days of their plasma donation for the presence of SARS-CoV-2 RNA.

Of the 2,250 samples tested, 196 (8.7%) were RNA repeat reactive, with RNA prevalence increasing from 1% in March 2020 to 15% in March 2021. The median estimated viral load in the 196 RNA repeat-reactive plasma samples was 6 gEq/mL, with 90% of samples having an estimated viral load of 18 gEq/mL or lower. No infectious virus was detected in plasma from RNAemic donors.

To address the theoretical risk of transfusion transmission of COVID-19, investigators tested the ability of plasma from RNA-positive units to infect a permissive cell line in vitro and an engineered mouse model in vivo. Inoculation of permissive cell lines produced less than 0.7–7 plaque-forming units (PFU)/mL and in susceptible mice less than 100 PFU/mL in RNA-positive plasma based on limits of detection in these models. According to the authors, the findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection.

“Failure to infect is likely due to the low level of virus in plasma (less than 1 PFU, with 100 PFU being the lowest dose at which we detected infection after intraperitoneal exposure to cultured virus),” the authors wrote. “The combination of the lack of infectivity in vitro and in vivo of the RNA-positive plasma, the low levels of RNA detected in these samples, and the poor transmission of infectious SARS-CoV-2 via intravenous routes all suggest little to no risk of transfusion transmission of this virus.”

Investigators concluded that the findings support the current policy of not testing blood donor products for SARS-CoV-2 RNA.