No evidence of SARS‐CoV‐2 transmission through transfusion of human blood products: A systematic review

Abstract The presence of viral nucleic material in the circulation poses a theoretical risk of transmission through transfusion. However, little is known about the possibility of the actual transmission through transfusion or transplantation of blood products. A PROSPERO registered systematic review pooled evidence from PubMed/MEDLINE, Google Scholar and CINAHL. The search included studies on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission through human blood products. In total 537 studies were extracted, and only eight articles (1.5%) were eligible for the final analysis. A total of 14 patients received blood products from coronavirus disease‐2019 (COVID‐19) virus‐positive donors, and six (42.9%) tested negative for COVID‐19 RT‐PCR for up to 14 days post‐transfusion/transplantation. There were no documented clinical details on the COVID‐19 test for eight (57.1%) blood products recipients. Of the eight patients, none of them developed any COVID‐19‐related symptoms. In conclusion, there is limited evidence of transfusion transmission of SARS‐CoV‐2 via human blood products. Consolidation of further evidence, as it emerges, is warranted.


Design
A systematic approach was engaged in searching the literature to try to answer a research question: 'What is the likelihood of SARS-CoV-2 transmission through human blood products?' . The review protocol was developed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. The protocol is registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/: PROSPERO database registration number: CRD42020223479).

Search strategy
A systematic evidence search was done using three strategies.

Eligibility criteria and study selection
The inclusion criteria were based on studies describing blood or HSC donors with confirmed SARS-CoV-2 and recipients of blood or HSC from donors with confirmed SARS-CoV-2 within 14 days of donation. The duration was chosen owing to the average maximum time it takes for the symptomatic presentation of COVID-19 [17]. Recipients of blood or HSC with known exposure to cases or suspects of SARS-CoV-2 and/or tested positive for SARS-CoV-2 before transfusion were excluded. Study selection was managed using Covidence software (Australia) where two independent reviewers (WFM and BJN) evaluated articles for potential inclusion by screening titles and abstracts followed by assessment of full-text articles to determine eligibility for final inclusion. Between each assessment, results were discussed to reach a consensus on the interpretation of inclusion criteria.
Based on the availability of literature, the review included letter to the editor, correspondence, editorial and research articles including case reports. Reviews and studies whose data were obtained from animal and in-vitro studies were excluded.

Data management
Duplicate publications were identified and removed using Covidence software (Australia). Identified publications were analyzed using criteria based on blood or HSC donors with confirmed SARS-CoV-2 and recipients of blood or HSC from donors with confirmed SARS-CoV-2 and maximum correspondence with inclusion criteria and minimal risk of bias ( Figure 1).

Quality assessment
The quality of the included studies (risk of bias) was assessed using the Newcastle Ottawa Scale adapted for cross-sectional studies (additional file S2) as described elsewhere [18]. The tool was customized to assess studies on (SARS-CoV-2) transmission through human blood products. The risk of bias was evaluated by two independent reviewers (WFM and BJN). Discrepancies were resolved by consensus, and/or consulting a third reviewer (GMB) where necessary  studies included, two (25%) were case series [18,25], and six (75%)

Suspected transfusion transmission of SARS-CoV-2
A total of 14 patients received blood products from COVID-19 virus-  (Table 1).
Of the six patients who tested negative, patient number one [20] was a 57-year-old male who had relapsed mantle cell lymphoma and

DISCUSSION
To the best of our knowledge, this is the first systematic review doc- CoV through blood product transfusion [11,18,26]. This is despite the demonstrated presence of viral RNA in the blood of infected individuals [8,9,27].
The current review included studies describing various types of donated blood products, including whole blood, platelets, granulocytes and mobilized peripheral blood stem cells from COVID-19 positive donors. One study [19] reported the blood component (platelet) from the COVID-19 positive donor was pathogen-reduced before being transfused to the recipient; however, the technique was not explained nor the effectiveness of the technique against SARS-CoV elaborated.
Whether the currently employed post-donation processing of blood components and stem cells and pathogen reduction methods can deactivate SAR-CoV and prevent transmission is yet to be determined.
Furthermore, half of the studies included in the current review used a nasal swab to test donors for COVID-19 infection [18,21,22,25]. One study [19] tested plasma, and two [23,24] used RT-PCR for testing; however, the latter did not report the type of specimen used.
Testing the presence of the virus antigen in the blood product being The small number of studies and participants obtained and the type of study designs (low-quality study designs, i.e., retrospective in nature) limit the conclusions of the current review. Nevertheless, being the first review that gathers evidence of COVID-19 transmission in blood products, the findings are a key in building evidence that examines the possibility of transmission of SARS-CoV-2 through blood products. This is particularly useful in the development of donor deferral criteria for blood donation agencies and combating the shortage and wastage of blood products, which are already limited in most regions.

CONCLUSION
There is limited evidence of transfusion transmission of SARS-CoV-

CONFLICT OF INTEREST
The authors declare that they have no competing interests.

AUTHORS CONTRIBUTIONS
William Frank Mawalla and Belinda J. Njiro designed the study protocol, conducted data extraction and synthesis. William Frank Mawalla drafted the narrative synthesis. George M. Bwire participated in revising the protocol, revising the narrative synthesis and manuscript.
Ahlam Nasser performed a data search and revised the manuscript.
Bruno F. Sunguya participated in protocol development and revised the narrative synthesis. All authors have read and approved the final version of this manuscript

DATA AVAILABILITY STATEMENT
All data sets used and/or analyzed in this review are provided in the main manuscript and its supplementary materials (Additional file 1 and 2).