Frequent detection but lack of infectivity of SARS-CoV-2 RNA in presymptomatic, infected blood donor plasma
Paula Saá, Rebecca V. Fink, Sonia Bakkour, Jing Jin, Graham Simmons, Marcus O. Muench, Hina Dawar, Clara Di Germanio, Alvin J. Hui, David J. Wright, David E. Krysztof, Steven H. Kleinman, Angela Cheung, Theresa Nester, Debra A. Kessler, Rebecca L. Townsend, Bryan R. Spencer, Hany Kamel, Jacquelyn M. Vannoy, Honey Dave, Michael P. Busch, Susan L. Stramer, Mars Stone, Rachael P. Jackman, Philip J. Norris, for the NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)
Paula Saá, Rebecca V. Fink, Sonia Bakkour, Jing Jin, Graham Simmons, Marcus O. Muench, Hina Dawar, Clara Di Germanio, Alvin J. Hui, David J. Wright, David E. Krysztof, Steven H. Kleinman, Angela Cheung, Theresa Nester, Debra A. Kessler, Rebecca L. Townsend, Bryan R. Spencer, Hany Kamel, Jacquelyn M. Vannoy, Honey Dave, Michael P. Busch, Susan L. Stramer, Mars Stone, Rachael P. Jackman, Philip J. Norris, for the NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)
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Research Article

Frequent detection but lack of infectivity of SARS-CoV-2 RNA in presymptomatic, infected blood donor plasma

Abstract

Respiratory viruses such as influenza do not typically cause viremia; however, SARS-CoV-2 has been detected in the blood of COVID-19 patients with mild and severe symptoms. Detection of SARS-CoV-2 in blood raises questions about its role in pathogenesis as well as transfusion safety concerns. Blood donor reports of symptoms or a diagnosis of COVID-19 after donation (post-donation information, PDI) preceded or coincided with increased general population COVID-19 mortality. Plasma samples from 2,250 blood donors who reported possible COVID-19–related PDI were tested for the presence of SARS-CoV-2 RNA. Detection of RNAemia peaked at 9%–15% of PDI donors in late 2020 to early 2021 and fell to approximately 4% after implementation of widespread vaccination in the population. RNAemic donors were 1.2- to 1.4-fold more likely to report cough or shortness of breath and 1.8-fold more likely to report change in taste or smell compared with infected donors without detectable RNAemia. No infectious virus was detected in plasma from RNAemic donors; 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. These findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection.

Authors

Paula Saá, Rebecca V. Fink, Sonia Bakkour, Jing Jin, Graham Simmons, Marcus O. Muench, Hina Dawar, Clara Di Germanio, Alvin J. Hui, David J. Wright, David E. Krysztof, Steven H. Kleinman, Angela Cheung, Theresa Nester, Debra A. Kessler, Rebecca L. Townsend, Bryan R. Spencer, Hany Kamel, Jacquelyn M. Vannoy, Honey Dave, Michael P. Busch, Susan L. Stramer, Mars Stone, Rachael P. Jackman, Philip J. Norris, for the NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)

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Figure 6

No infection observed with exposure to SARS-CoV2 RNA–positive human plasma.

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No infection observed with exposure to SARS-CoV2 RNA–positive human plas...
(A–C) K18-hACE2–Tg IFNAR-KO mice were infected with 1.1 × 102 PFU, 1.1 × 104 PFU, or 1.1 × 105 PFU intravenously, or 1.1 × 102 PFU intranasally with the B1.1.7 variant of SARS-CoV-2. (D–F) K18-hACE2–Tg IFNAR-KO mice were infected with 1.1 × 100 PFU, 1.1 × 101 PFU, 1.1 × 102 PFU, 1.1 × 103 PFU, 1.1 × 104 PFU, or 1.1 × 105 PFU intraperitoneally with the B1.1.7 variant of SARS-CoV-2 or given 500 μL SARS-CoV2 RNA–positive human plasma intraperitoneally (6 samples into 2 mice each were tested). Unexposed IFNAR-KO littermates that do not carry the K18-hACE gene (noncarriers) were used as negative controls. (A and D) Weights were measured daily and the percentage weight change was calculated for each mouse over time, with mean change in weights and standard deviation plotted for each group. (B and E) Percentage survival over time by group. (C and F) At indicated time points, 20 μL of EDTA whole blood was collected, RNA was isolated, and SARS-CoV2 RNA levels were measured by qRT-PCR. Values are plotted for each mouse. × indicates nonsurviving mouse. Dashed line indicates maximum value detected among 63 negative blood sample controls plus 0.5 and was used as a cutoff for positive signal. When no viral RNA was detected, a value of 0.5 was assigned.