Our systematic review provides a summary of the current state of research with blockchain technology for both COVID-19-related and non-COVID-19-related applications in health care. Key findings are, first, that COVID-19-related research clearly has different areas of emphasis compared with non-COVID-19-related research, and focuses predominantly on pandemic control and surveillance, contact tracing, and immunity or vaccine passports. Although some reported applications (eg, vaccine supply chain monitoring) could be considered extensions from non-COVID-19-related indications, most applications (eg, COVID-19 immunity certificates or movement monitoring and control) are quite distinct.
12
- Shamsi K
- Khorasani KE
- Shayegan MJ
A secure and efficient approach for issuing KYC token as COVID-19 health certificate based on stellar blockchain network.
,
13
- Alsamhi SH
- Lee B
- Guizani M
- Kumar N
- Qiao Y
- Liu X
Blockchain for decentralized multi-drone to combat COVID-19.
Second, electronic medical records are the most common focus of blockchain research, but the scope of research has been substantially expanded to include other applications in the past 4 years. These applications include areas of blockchain application such as telemedicine
14
- Celesti A
- Ruggeri A
- Fazio M
- Galletta A
- Villari M
- Romano A
Blockchain-based healthcare workflow for tele-medical laboratory in federated hospital IoT clouds.
,
15
- Lin H
- Zhang H
- Yan H
- et al.
A secure online treatment blockchain service.
,
16
A Novel structure of blockchain applied in vaccine quality control: double-chain structured blockchain system for vaccine anticounterfeiting and traceability.
,
17
- Sylim P
- Liu F
- Marcelo A
- Fontelo P
Blockchain technology for detecting falsified and substandard drugs in distribution: pharmaceutical supply chain intervention.
and supply chain monitoring.
16
A Novel structure of blockchain applied in vaccine quality control: double-chain structured blockchain system for vaccine anticounterfeiting and traceability.
,
17
- Sylim P
- Liu F
- Marcelo A
- Fontelo P
Blockchain technology for detecting falsified and substandard drugs in distribution: pharmaceutical supply chain intervention.
These differences in the applications of blockchain technology are illustrated in the appendix (p 42). Third, the majority of the studies reviewed demonstrated technical simulation results, but only a few were actually trialled in clinical settings. Finally, most of the blockchain platforms were designed either on Ethereum or Hyperledger. However, an important proportion of studies did not specify the exact platform used, which might be due to an absence of standardised reporting guidelines.
COVID-19-related applications of blockchain
The COVID-19 pandemic has necessitated the coordination and management of large amounts of data. First, these data are usually sensitive, but need to be easily verifiable and managed transparently.
8
- Ting DSW
- Carin L
- Dzau V
- Wong TY
Digital technology and COVID-19.
,
18
- Mahmood S
- Hasan K
- Colder Carras M
- Labrique A
Global preparedness against COVID-19: we must leverage the power of digital health.
However, if these data management platforms were to grant full access of the data to central authorities, important privacy concerns could be raised, which might in turn be counter-productive.
19
BlueTrace: a privacy-preserving protocol for community-driven contact tracing across borders.
,
20
- Idrees SM
- Nowostawski M
- Jameel R
Blockchain-based digital contact tracing apps for COVID-19 pandemic management: issues, challenges, solutions, and future directions.
To address these concerns, Garg and colleagues
21
- Garg C
- Bansal A
- Padappayil RP
COVID-19: prolonged social distancing implementation strategy using blockchain-based movement passes.
developed a blockchain-based movement pass that relies on smart contracts and tokens (tokens-based movement passes) that dispense the need for personal particulars for verification purposes. Separately, Xu and colleagues
22
- Xu H
- Zhang L
- Onireti O
- Fang Y
- Buchanan WB
- Imran MA
BeepTrace: blockchain-enabled privacy-preserving contact tracing for COVID-19 pandemic and beyond.
demonstrated a viable blockchain platform (with data acquisition via IoT) that can desensitise a user’s identity and location information through its hash function, thereby ensuring the protection of the identity of patients with COVID-19 and the privacy of the public in a decentralised environment. These examples highlight how blockchain solutions can overcome the challenge of collating verifiable, yet de-identified, tracking data.
Second, the implementation of rapid, widespread testing and vaccination strategies might also require the introduction of health and immunity certificates. Blockchain technology can provide a secure and decentralised environment for cross-border verification of COVID-negative or immunity status.
23
- Eisenstadt M
- Ramachandran M
- Chowdhury N
- Third A
- Domingue J
COVID-19 antibody test/vaccination certification: there’s an app for that.
,
24
- Hasan HR
- Salah K
- Jayaraman R
- et al.
Blockchain-based solution for COVID-19 digital medical passports and immunity certificates.
,
25
- Bansal A
- Garg C
- Padappayil RP
Optimizing the implementation of COVID-19 “immunity certificates” using blockchain.
Eisenstadt and colleagues
23
- Eisenstadt M
- Ramachandran M
- Chowdhury N
- Third A
- Domingue J
COVID-19 antibody test/vaccination certification: there’s an app for that.
used a consortium, Ethereum-based blockchain architecture combined with a mobile application to achieve instant verification of tamper-proof test results, achieved through the use of public or private key pairs generalised to avoid restrictive ownership of sensitive keys or data. In a separate, unique study by Chaudhari and colleagues,
26
- Chaudhari S
- Clear M
- Bradish P
- Tewari H
Framework for a DLT based COVID-19 passport.
the authors stored COVID-19 vaccination details of each recipient on-chain on a publicly readable platform, and authenticated users and anonymously located vaccination records with an iris extraction technique, which allowed them to hide the input and avoid leakage of any personal identifiable information. Concerns about scalability, latency, and storage were also addressed in a separate study, where Hyperledger Fabric architecture and a distributed system for file storage and access (Interplanetary File Storage)
27
No authors listed
What is IPFS?.
were adopted in a simulated, high-travel volume European Member State environment, achieving satisfactory results at a peak of 100 transactions per s.
28
- Hernández-Ramos JL
- Karopoulos G
- Geneiatakis D
- Martin T
- Kambourakis G
- Fovino IN
Sharing pandemic vaccination certificates through blockchain: case study and performance evaluation.
Third, there is greater scrutiny over the management of supply chains for vital supplies, such as personal protective equipment, essential medications, and COVID-19 vaccines.
29
Ensuring access to medications in the US during the COVID-19 pandemic.
,
30
- Gordon DE
- Jang GM
- Bouhaddou M
- et al.
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
,
31
Addressing COVID-19 drug development with artificial intelligence.
,
32
Applying blockchain technology to address the crisis of trust during the COVID-19 pandemic.
,
33
- Kovács G
- Falagara Sigala I
Lessons learned from humanitarian logistics to manage supply chain disruptions.
Precise monitoring can be done at a granular level with IoT, oracles, and Application Programming Interfaces for each individual vial or package. In a study by Antal and colleagues,
34
- Antal CD
- Cioara T
- Antal M
- Anghel I
Blockchain platform for COVID-19 vaccine supply management.
IoT sensor devices were combined with self-enforcing smart contracts on an Ethereum blockchain platform to achieve end-to-end tracking and visibility, thereby ensuring the veracity of COVID-19 vaccine distribution data. In addition, the proposed system also addressed a major concern about such vaccines, by also supporting on-chain recording of side-effects. Ahmad and colleagues
35
- Ahmad RW
- Salah K
- Jayaraman R
- Yaqoob I
- Omar M
- Ellahham S
Blockchain-based forward supply chain and waste management for COVID-19 medical equipment and supplies.
instead demonstrated the use of blockchain to manage an entire forward supply chain and waste management of COVID-19-related medical equipment and supplies. Similarly, their blockchain was designed with Ethereum architecture in combination with smart contracts, highlighting the versatility of Ethereum.
Fourth, a secure, decentralised, peer-to-peer network could also be used for telemedicine initiatives, including test kit management
14
- Celesti A
- Ruggeri A
- Fazio M
- Galletta A
- Villari M
- Romano A
Blockchain-based healthcare workflow for tele-medical laboratory in federated hospital IoT clouds.
and medical data sharing amongst trusted stakeholders.
36
Kumar R, Tripathi R. A Secure and distributed framework for sharing COVID-19 patient reports using consortium blockchain and IPFS. 6th International Conference on Parallel, Distributed and Grid Computing; online; 6–8 Nov, 2020: 231–36.
,
37
Christodoulou K, Christodoulou P, Zinonos Z, Carayannis EG, Chatzichristofis SA. Health information exchange with blockchain amid Covid-19-like pandemics. 16th International Conference on Distributed Computing in Sensor Systems; Marina del Rey, CA, USA; May 25–27, 2020: 412–17.
In a study by Kumar and Tripathi,
36
Kumar R, Tripathi R. A Secure and distributed framework for sharing COVID-19 patient reports using consortium blockchain and IPFS. 6th International Conference on Parallel, Distributed and Grid Computing; online; 6–8 Nov, 2020: 231–36.
a consortium network blockchain was created for the sharing of COVID-19-related reports (eg, chest CT scans). The blockchain was designed to identify and validate these reports before they were stored on-chain, by comparing the similarity of the perceptual hash of each report with existing on-chain perceptual hashes, thereby filtering out non-COVID-19-related reports. Lee and colleagues
38
- Lee HA
- Kung HH
- Lee YJ
- et al.
Global infectious disease surveillance and case tracking system for COVID-19: development study.
created a global International Patient Summary electronic medical record system using Proof of Authority consensus. The system supported real-time uploading from clinic electronic medical records systems using a combination of open Application Programming Interface and Fast Healthcare Interoperability Resources. This way, they could provide timely public updates on the pandemic, assist authorities with dynamic adjustment of health-care policies, and support pandemic research.
Non-COVID-19-related applications of blockchain
Apart from the immediate focus on COVID-19, blockchain applications in digital health have been described in several other key health-care domains: authentication and electronic medical records management;
39
A blockchain framework for patient-centered health records and exchange (HealthChain): evaluation and proof-of-concept study.
,
40
- Mohsin AH
- Zaidan AA
- Zaidan BB
- et al.
Based blockchain-PSO-AES techniques in finger vein biometrics: a novel verification secure framework for patient authentication.
clinical trial research and consent management;
41
- Zhuang Y
- Sheets LR
- Shae Z
- Chen YW
- Tsai JJP
- Shyu CR
Applying blockchain technology to enhance clinical trial recruitment.
,
42
- Zhuang Y
- Sheets L
- Shae Z
- Tsai JJP
- Shyu CR
Applying blockchain technology for health information exchange and persistent monitoring for clinical trials.
health-care insurance claims processing;
43
Mistore: a blockchain-based medical insurance storage system.
research data transfer and AI model development;
44
- Tan TE
- Anees A
- Chen C
- et al.
Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.
,
45
- Kuo TT
- Gabriel RA
- Cidambi KR
- Ohno-Machado L
EXpectation Propagation LOgistic REgRession on permissioned blockCHAIN (ExplorerChain): decentralized online healthcare/genomics predictive model learning.
genomics;
46
- Jin XL
- Zhang M
- Zhou Z
- Yu X
Application of a blockchain platform to manage and secure personal genomic data: a case study of LifeCODE.ai in China.
supply chain encryption for medical supplies;
16
A Novel structure of blockchain applied in vaccine quality control: double-chain structured blockchain system for vaccine anticounterfeiting and traceability.
,
47
- Tseng JH
- Liao YC
- Chong B
- Liao SW
Governance on the drug supply chain via Gcoin blockchain.
and mobile health and IoT.
46
- Jin XL
- Zhang M
- Zhou Z
- Yu X
Application of a blockchain platform to manage and secure personal genomic data: a case study of LifeCODE.ai in China.
,
48
- Dwivedi AD
- Srivastava G
- Dhar S
- Singh R
A decentralized privacy-preserving healthcare blockchain for IoT.
First, blockchain technology is an effective digital technology to manage electronic medical records, with the ability to assign controlling rights to patients.
49
- Chenthara S
- Ahmed K
- Wang H
- Whittaker F
- Chen Z
Healthchain: a novel framework on privacy preservation of electronic health records using blockchain technology.
Such studies identified in this systematic review varied in their approach, with strategies including the use of shared keys in the event of the death of the patient (key-holder);
50
Medical data management on blockchain with privacy.
electronic medical records maintenance in a unified viewpoint;
51
- Roehrs A
- da Costa CA
- da Rosa Righi R
OmniPHR: a distributed architecture model to integrate personal health records.
secure cloud-based electronic medical records;
52
Secure cloud-based EHR system using attribute-based cryptosystem and blockchain.
enhanced interoperability;
53
Jin H, Xu C, Luo Y, Li P, Cao Y, Mathew J. Toward secure, privacy-preserving, and interoperable medical data sharing via blockchain. IEEE 25th International Conference on Parallel and Distributed Systems; Tianjin; Dec 4–6, 2019: 852–61.
fine-grained access;
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- Malamas V
- Kotzanikolaou P
- Dasaklis TK
- Burmester M
A hierarchical multi blockchain for fine grained access to medical data.
and privacy-preservation techniques.
50
Medical data management on blockchain with privacy.
,
55
- Liu H
- Crespo RG
- Martínez OS
Enhancing privacy and data security across healthcare applications using blockchain and distributed ledger concepts.
,
56
Towards secure and privacy-preserving data sharing in e-health systems via consortium blockchain.
In one of the few clinically trialled blockchain platforms we found, Lo and colleagues
57
- Lo YS
- Yang CY
- Chien HF
- Chang SS
- Lu CY
- Chen RJ
Blockchain-enabled iWellChain framework integration with the National Medical Referral System: development and usability study.
integrated medical data from the National Medical Record system in Taiwan with clinic electronic medical records to create an alliance-based medical referral system. They also used a patient-centric approach by further developing an additional blockchain-based decentralised application to grant access rights and data control to patients, which allowed them to demonstrate a viable decentralised referral system and strong patient interest in accessing their own medical data.
Second, application of blockchain has been explored for the management of clinical trials to potentially improve transparency and auditability. Benchoufi and colleagues
58
- Benchoufi M
- Porcher R
- Ravaud P
Blockchain protocols in clinical trials: transparency and traceability of consent.
used the automatic execution of blockchain to monitor clinical trial events, including voluntary consent, in a pre-set chronological order. This automatic execution could be further extrapolated for use in the context of clinical consent for procedures or treatment to combat medicolegal fraud.
59
- Velmovitsky PE
- Miranda PADSES
- Vaillancourt H
- Donovska T
- Teague J
- Morita PP
A blockchain-based consent platform for active assisted living: modeling study and conceptual framework.
In health-care insurance, a distributed ledger could improve the claims process by enhancing security and decreasing the overall time taken to reach settlement.
60
- Thenmozhi M
- Dhanalakshmi R
- Geetha S
- Valli R
Implementing blockchain technologies for health insurance claim processing in hospitals.
When insurance claims are recorded immutably on-chain, the required transparency to deter fraudulent activities might be reached.
61
- Mackey TK
- Miyachi K
- Fung D
- Qian S
- Short J
Combating health care fraud and abuse: conceptualization and prototyping study of a blockchain antifraud framework.
However, as highlighted by Mackey and colleagues,
61
- Mackey TK
- Miyachi K
- Fung D
- Qian S
- Short J
Combating health care fraud and abuse: conceptualization and prototyping study of a blockchain antifraud framework.
the feasibility of such systems is likely to hinge on their ability to establish interoperability with off-chain databases.
Third, blockchain technology could facilitate medical research collaboration, especially in the field of AI development with privacy-preserving technologies. Several of the studies identified combined federated learning with blockchain technology to improve AI development and generalisability.
62
- Rahman MA
- Hossain MS
- Islam MS
- Alrajeh NA
- Muhammad G
Secure and provenance enhanced internet of health things framework: a blockchain managed federated learning approach.
,
63
- Polap D
- Srivastava G
- Yu K
Agent architecture of an intelligent medical system based on federated learning and blockchain technology.
Kumar and colleagues,
64
- Kumar R
- Wang W
- Kumar J
- et al.
An integration of blockchain and AI for secure data sharing and detection of CT images for the hospitals.
however, suggested that local model weights be distributed on a decentralised blockchain network. Tan and colleagues
44
- Tan TE
- Anees A
- Chen C
- et al.
Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.
showed proof of concept through a permissioned blockchain platform to allow secure data transfer, transparent reporting of AI model performance, and model transfer and testing on an external dataset, which might provide health regulators (eg, the US Food and Drug Administration) with a means to effectively audit and verify future diagnostic performance of AI algorithms for regulatory approval. To further enhance privacy-preservation and decentralisation of AI training, Warnat-Herresthal and colleagues
65
- Warnat-Herresthal S
- Schultze H
- Shastry KL
- et al.
Swarm Learning for decentralized and confidential clinical machine learning.
proposed a combination of blockchain and swamp learning as the next evolution beyond federated learning, in which way the central custodian is dispensed with and the data and parameters are kept at the edge.
Fourth, another area of blockchain research interest is the class of so-called omics technologies (eg, genomics, proteomics, and metabolomics) and genetics. This interest in blockchain technology stems from concerns about the ability of centralised databases to manage such highly confidential data.
66
- Ozercan HI
- Ileri AM
- Ayday E
- Alkan C
Realizing the potential of blockchain technologies in genomics.
,
67
- Aiello M
- Cavaliere C
- D’Albore A
- Salvatore M
The challenges of diagnostic imaging in the era of big data.
,
68
Big data and machine learning algorithms for health-care delivery.
,
69
- Kruse CS
- Goswamy R
- Raval Y
- Marawi S
Challenges and opportunities of big data in health care: a systematic review.
In one of the few studies to use commercially available blockchain platforms, Jin and colleagues
46
- Jin XL
- Zhang M
- Zhou Z
- Yu X
Application of a blockchain platform to manage and secure personal genomic data: a case study of LifeCODE.ai in China.
described the use of genomic blockchain Life Code, which is designed with the Ethereum architecture. The platform facilitated access to genomic data by establishing a secure trading system through the use of tokens. Separately, Glicksberg and colleagues
70
- Glicksberg BS
- Burns S
- Currie R
- et al.
Blockchain-authenticated sharing of genomic and clinical outcomes data of patients with cancer: a prospective cohort study.
conducted a prospective cohort study for dissemination of de-identified clinical and genomic data of patients with late-stage cancer and reported two key findings. The completeness of the electronic medical records extracted by the blockchain platform was comparable with registry reports, which allowed rapid dissemination of real-world data. Furthermore, they reported that patients with cancer were increasingly willing to share their data for the development of medical knowledge.
Fifth, the medical supply chain, especially for pharmaceutical drugs, is particularly complex, with widely distributed geographical networks. During the assessment of blockchain viability, Tseng and colleagues
47
- Tseng JH
- Liao YC
- Chong B
- Liao SW
Governance on the drug supply chain via Gcoin blockchain.
also noted that the use of traditional devices, such as barcodes and radiofrequency identification, have so far failed to prevent counterfeit drug fiascos, even in high-income regions, such as Taiwan. They instead showed the viability of a Proof of Work consensus using a commercial blockchain platform (GCoin) and further suggested the development of a smart-contract-based open-governance surveillance net. Lower-income countries, such as the Philippines, also face similar drug safety concerns. To address this issue, Sylim and colleagues
17
- Sylim P
- Liu F
- Marcelo A
- Fontelo P
Blockchain technology for detecting falsified and substandard drugs in distribution: pharmaceutical supply chain intervention.
embarked on the development of a pharmacological surveillance blockchain system to support information sharing along the official drug distribution network, using either delegated Proof of Stake or Practical Byzantine Fault Tolerance to achieve scalability and adaptability. In these examples, blockchain technology serves to create a trust mechanism to track and authenticate pharmaceuticals while protecting the supply chain from malicious attacks.
Finally, patient-centric care requires close monitoring. Advances in IoT technology supported by edge or fog computing serve to bring blockchain functionality to the patient level. Ali and colleagues
71
- Ali MS
- Vecchio M
- Putra GD
- Kanhere SS
- Antonelli F
A decentralized peer-to-peer remote health monitoring system.
combined blockchain with medical IoT to deliver remote patient monitoring, such as cardiac monitoring, sleep apnoea testing, and electroencephalogram monitoring. In their study, they addressed inherent blockchain and IoT issues, such as privacy and scalability, by adopting a hybrid of on-chain (public blockchain for authentication and record keeping) and off-chain solutions (Tor hidden services for data transfer). Although most of the studies included in this Review were designed with either Ethereum or Hyperledger, Brogan and colleagues
72
- Brogan J
- Baskaran I
- Ramachandran N
Authenticating health activity data using distributed ledger technologies.
explored the use of the IOTA protocol (open-source distributed ledger technology), which is an inexpensive platform specifically designed for computationally light-weight IoT. With this blockchain platform, they were able to broadcast and receive authenticated, encrypted activity data from a wearable device. In a broader setting, such functionality might enable remote monitoring and mobile health for clinical or research purposes in the future.
Strengths and weaknesses
We herein provide a comprehensive, up-to-date systematic review of active blockchain research in various health-care domains, which helps to provide a perspective on the current research landscape on this topic, including the state of research and overall direction. Hopefully, this systematic review will allow the identification of areas that require greater attention or that might hold strong potential for real-world implementation. In addition, we explored COVID-19-specific applications, which are currently key drivers for the adoption of blockchain into the otherwise traditionally conservative health-care system. Furthermore, our systematic review described both COVID-19-related and non-COVID-19-related health-care blockchain applications. A substantial proportion of these COVID-19-specific use cases is likely to find durable relevance in the post-pandemic world, such as in vaccine and pharmaceutical supply chain management, contact tracing, and telemedicine recording (of the notes documented during consultation or the off-chain storage locations of large files). This work is thus the first to provide a comprehensive review of the development of blockchain in health care, and of how the evolving pandemic continues to shape the role of this technology. The little availability of original studies that show clinical implementation provides an indication of the relative infancy of blockchain technology in health care and of barriers toward widespread acceptance. Because of time limitations, we were not able to conduct a further exhaustive search across other bibliographical database that might provide additional valuable information. In addition, non-peer-reviewed literature was included in our evaluation, which could affect the robustness of the data. Finally, the absence of standardised research reporting for crucial technical components, such as blockchain consensus protocols and platforms, limits the generalisability of this systematic review, which might contribute to a disconnection between the early-stage championing of blockchain and validated, real-world research progress. Nevertheless, we believe that the literature assessed in this systematic review represents a strong foundation for blockchain as an enabling platform for a broad spectrum of health-care applications, both during and beyond the COVID-19 pandemic.
