We are living in an era of overlapping pandemics. Like oceanic currents, some flow and spread discreetly under the surface. Others, like tsunamis, wreak havoc as they pass. Populations have been decimated by microscopic pathogens, but we have come out on the other side, stronger and more knowledgeable. Unfortunately, the current COVID-19 pandemic reaffirms that we still have a lot to learn on how best to control pandemics and combat emerging pathogens. If we look under the surface, below the blaring crisis caused by SARS-CoV-2, more pandemics are ongoing. Silently, many viruses are circulating in the population and causing their slow but steady devastation. One such group of blood-borne pathogens are hepatitis viruses.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are of particular concern, as they have established lifelong infection in over 300 million people worldwide. Globally, chronic viral hepatitis is the leading cause of liver cancer and liver failure, accounting for approximately 1.1 million deaths per year (1). The study of these viruses has led to many scientific advancements, such as an effective vaccine for HBV and curative treatments for HCV. These achievements prompted the World Health Organization’s (WHO) commitment to eliminate viral hepatitis as a public health threat by 2030 (2). To improve standard of care and achieve these viral hepatitis elimination targets, we need to take some lessons from the COVID-19 pandemic.
How have HBV and HCV research provided useful tools to combat COVID-19?
Broad acting antivirals
Antivirals can be repurposed to target pathways that are conserved across several viruses. As such, the nucleoside analogs Remdesivir and Sofosbuvir, originally developed to target RNA viruses including Ebola and HCV (3), have been used to treat COVID-19 (4, 5). RNA viruses often share similar features, enabling us to target them with the same compounds. Many other antivirals that are being used to treat chronic HBV and HCV infection are also in phase II/III clinical trials for the treatment of COVID-19 (6-9).
Vaccine development platforms
Beyond antivirals, vaccines play a key role in eliminating any viral threat. The HBV vaccine was the first approved vaccine to use recombinant DNA technology, which paved the way for subsequent vaccines, including COVID-19 (10, 11). The ChAdOx1 vector was initially developed at the University of Oxford as a delivery vector for an HCV vaccine candidate. Although this platform did not prevent chronic HCV infection, it was subsequently used in the Oxford-AstraZeneca COVID-19 vaccine with great success (12, 13). Finally, mRNA vaccines produced by Pfizer-BioNTech and Moderna may have reached approval for the first time; however, they have been under development against several pathogens, including HCV (14, 15). Thus, both HBV and HCV vaccine platforms have provided a steppingstone to accelerate COVID-19 vaccine development. In turn, the advancements in mRNA vaccine technologies can be applied in the future to produce an efficacious HCV vaccine.
Genotyping
Viruses that replicate using an RNA polymerase, like SARS-CoV-2, HBV, and HCV, are prone to changes in their genome called mutations. Many of these mutations can be harmful to the virus, while some provide increased fitness. Advantageous mutations can become prevalent in the viral population, leading to variants or even different genotypes and subtypes, as is the case for HBV and HCV. Effectively, different HBV or HCV genotypes are associated with various clinical outcomes such as disease severity and progression, or response to treatment (16). As such, genotyping is of great importance for providing optimal patient care and informed treatment. Previous knowledge about virus evolution has prompted surveillance of SARS-CoV-2 variants to identify mutations of concern and study their susceptibility to vaccines.
How can our response to the COVID-19 pandemic inform the future of HBV and HCV care?
Telemedicine
To reduce traveling and contacts, many activities were moved to a remote format during the COVID-19 pandemic — healthcare was no exception. Physician consultations were carried out remotely when possible, and this virtual approach has previously been shown to help lessen the stigma around various medical issues while making healthcare more accessible (17). This model comes with many benefits, such as reduced travel, clinic wait times, and anxiety related to HBV and HCV testing and treatment. Even in the post-COVID-19 era, we can look to implement telemedicine to simplify the viral hepatitis cascade of care.
Facilitated booking systems for testing and vaccination
Faced with the immense task of testing and vaccinating an entire population, provincial governments within Canada put in place an online system for individuals to book their appointments without any involvement of staff (18).
To prevent the spread of infectious pathogens, the first and most important step is to get tested. Historically, stigma and lack of access to testing have been some of the greatest barriers for the prevention, management, and treatment of infectious diseases (19). The COVID-19 pandemic has revolutionized the testing process by introducing mobile high-capacity testing centres at diverse locations with specific guidelines for vulnerable populations such as people experiencing homelessness, drive-through testing, home testing kits, and rapid antigen/RNA tests (20, 21). To improve the standard of care, these services should be expanded to include viral hepatitis testing and vaccination. Scaling up testing capacity should also be supported with increased efforts to ensure and improve linkage to care, which could greatly improve hepatitis elimination efforts.
Transparency and in-depth data tracking
Throughout the pandemic, the Canadian government has been extremely transparent by releasing daily counts of new infections, positive tests, hospitalizations, intensive care unit (ICU) occupancies, and deaths. COVID-19 regional hotspots and populations to be prioritized for vaccinations were also noted (22). This has improved disease awareness and democratized data such that targeted public health initiatives were implemented to further prevent virus spread.
On the contrary, HBV and HCV surveillance reporting is not routine nor timely in many regions across Canada. This impedes our ability to address outbreaks with adequate localized prevention, testing, linkage to care and treatment offerings (23, 24). Viral hepatitis testing should be included as part of regular medical check-ups for key populations and one-time universal testing for the general population (25, 26). Applying similar dashboards used for COVID-19 surveillance to support the routine and transparent reporting of viral hepatitis data could be a huge step towards normalizing hepatitis while increasing public engagement and progress towards elimination.
Concerted global efforts to accelerate evidence synthesis and support decision-making
Governments across the globe have been proactive during the COVID-19 pandemic to adopt public health measures, implement new models for testing and promote mass uptake of vaccination. Governments have thus relied upon access to the latest evidence to make informed decisions. Many international initiatives and networks (i.e. COVID-END) have emerged during the pandemic to accelerate evidence synthesis and support decision-making (27). Progress towards the global elimination of HBV and HCV is also contingent upon international coordination of efforts. Organizations like Action Hepatitis Canada and the World Hepatitis Alliance could draw upon the knowledge and experience acquired through such networks to engage with decision makers more effectively and, ultimately, optimize the global response to the HBV and HCV pandemics.
What has allowed us to respond so quickly to the COVID-19 pandemic?
The rapid spread of SARS-CoV-2 combined with a high fatality rate among certain populations called for a rapid global response from governments and the WHO (28). This response provided financing for emergency vaccine development that led to the administration of highly efficacious vaccines less than one year into the pandemic (29). Unlike COVID-19, chronic diseases like viral hepatitis take years to develop and lower an individual’s quality of life slowly but steadily (30). Symptoms of HBV/HCV usually do not appear until late-stage liver disease, at which point the consequences are unlikely to be reversible. Because of the slow progression and lack of early signs, viral hepatitis does not receive a similar urgency-influenced response from the government, and the amount of funding and public attention that it does get limits research and elimination efforts.
The COVID-19 pandemic has demonstrated that strong political will, high public awareness, and a rapid and concerted response from scientists and pharmaceutical companies can lead to unprecedented breakthroughs. Using the lessons from COVID-19, we could formulate new guidelines for dealing with other ongoing pandemics and important epidemics. By applying similar strategies to increase disease awareness among the public, we can collectively work towards the elimination of several viral threats and prepare for future pandemics.
Concluding remarks
Learning as much as we can about pandemics and taking meaningful steps towards protection against infection and control of disease spread are key elements of an elimination strategy. Although we are beginning to see the light at the end of the tunnel for COVID-19, other pandemics are ongoing, and “hepatitis can’t wait”. Applying lessons from the COVID-19 pandemic could not only accelerate our progress towards the elimination of viral hepatitis but also help us limit the damage of the next pandemic. Similar to the study of oceanic currents and winds to determine where the next tsunami will hit, public health and research efforts directed at HBV and HCV can help build protective structures to break the waves before they even reach the shore.
This open letter was co-authored by Marylin Rheault 1, Mohamed Abdelnabi 2, Jawaira Atif 3, Samaa Gobran 4, Zoë Greenwald 5, Guillaume Fontaine 6, Dahn Jeong 7, Charlotte Lanièce Delaunay 8, Gillian Kolla 9, Gayatri Marathe 10, Jean Damascene Makuza 11, Sabrina Mazouz 12, Sameh Mortazhejri 13, Jiafeng Li 14, Ching-Hsuan Liu 15, Michael Palmer 16, Ana Maria Passos-Castilho 17, Yasmin Saeed 18, Manolya Sag 19, Mohamed Shengir 20, Sasha Tejna Persaud Udheister 21, Hannah Louise Wallace 22, and Simmone D’souza 23.
Acknowledgements
The authors thank Dr Naglaa Shoukry, Dr Chris Richardson and Norma Choucha for their guidance in writing this letter.
Author affiliations
1 BSc (Honours), Department of Microbiology & Immunology, McGill University
2 MSc, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal.
3 BSc, PhD Candidate Fundamental Immunology, University of Toronto
4 BSc, MSc, PhD candidate, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada.
5 BSc, PhD Dalla Lana School of Public Health, University of Toronto
6 PhD, MSc, RN CIHR Banting Postdoctoral Research Fellow Clinical Epidemiology Program, Ottawa Research Institute Faculty of Medicine, University of Ottawa
7 MSc, School of Population and Public Health, University of British Columbia, British Columbia Centre for Disease Control
8 MPH Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine, McGill University
9 PhD, MPH, Postdoctoral Research Fellow, Canadian Institute for Substance Use Research, University of Victoria
10 MSc, ScM, Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine, McGill University
11 MD, MSc School of Population and Public Health, University of British Columbia
12 BSc, MSc, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM),
Montréal, Québec, Canada.
13 MD, MSc Clinical Epidemiology Program, Ottawa Hospital Research Institute Faculty of Medicine, University of Ottawa
14 BSc, PhD Ottawa Hospital Research Institute Faculty of Medicine, university of Ottawa.
15 MD, PhD Candidate Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
16 BSc, PhD Candidate Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
17 PhD, Postdoctoral Fellow Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital Department of Medicine, McGill University
18 BScPhm, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
19 BSc, MSc Candidate Department of Biochemistry, McGill University
20 MD, MSc, PhD candidate Division of Experimental Medicine, Department of medicine, McGill university
21 MSc, PhD Candidate, Biomedical Sciences, Faculty of Medicine, University of Montreal
22 BSc (Honours), PhD Candidate, Immunology and Infectious Diseases, Division of Biomedical Sciences, Faculty of Medicine, Memorial University
23 BSc (Honours), PhD Candidate, Microbiology, Immunology, and Infectious Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
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