Considerations on the SARS-CoV-2 Pandemic

Royston E. Carter, PhD

Manhattan, Kansas – Mr. Willy Valdivia-Granda, CEO of Orion Integrated Biosciences, and Dr. Jurgen Richt, Director of Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), experts in emerging infectious diseases and biodefense, have co-authored an important and wide-ranging perspective of the SARS-CoV-2 pandemic and its broader policy and biodefense implications and lessons that can be learned. In this paper published in the Vector-Borne and Zoonotic Diseases Journal, the authors advocate for improved biosurveillance for coronaviruses and other emerging pathogens, and also for international cooperation for the development of autonomous surveillance systems.

They also caution that in a rush to succeed, the development of vaccines must focus on limiting adverse outcomes via attention to coronavirus biology and host immune systems.

Orion is a specialized biodefense company headquartered in Kansas, with a growing presence in North Carolina and with over a decade experience in genomic analysis of infectious disease pathogens and development of data-driven analytical systems for near-real time risk assessment.

Mr. Valdivia explained “while coronaviruses were tracked by our analytical system RIGEL, early signals were detected as unknown pneumonic outbreak in China on December 31. The pattern was similar to an outbreak of pneumonic plague reported a few weeks earlier in Beijing; however, it was not until January 9 that we began to discuss this situation with high-level officials”.

This shows the complexity of biosurveillance, and was one of the reasons why the scientists decided to publish their perspective in the Vector-Borne and Zoonotic Diseases Journal, “We need more openness in the international reporting of diseases,” they said, noting that despite decades of dire warnings from the international scientific community and intelligence agencies, the world was not prepared for SARS-CoV-2.  “It is not a case of if but when another pandemic infectious disease will emerge,” they said.

The recommendations require a concerted and globally coordinated One Health approach involving scientists, physicians, veterinarians, and epidemiologists and, must be supported by International political will and resources appropriate for the effort. Furthermore, the data must be properly collected and turned into actionable information that is appropriately shared and used by governments and the international community to develop risk-based analysis and forecasting.

However, these types of information are highly dynamic and can be impacted by global activities and events such as trade, health capacity in countries and many other local and global factors. Therefore, the timeliness and accuracy and hence value of the information can be negatively impacted by secrecy, deliberate misinformation, and propaganda efforts. Many of these recommendations are based on lessons learned by Orion’s more than 10 years building and expanding a biodefense-orientated computational enterprise named RIGEL Today, SARS-CoV-2 had spread to more than 200 countries, infected more than 4 million people, and caused more than 450,000 fatalities, and as we all know these statistics continue to grow. Despite substantial mitigation efforts such as isolation measures and social distancing to slow the spread the human and economic toll has not yet abated. Dr. Richt pointed out that “lessons can be learned from the SARS-CoV-2 pandemic, which could have an immediate impact and enhance pandemic preparedness for the future. SARS-CoV-2 was not the first and it will not be the last emerging pathogen that has spilled over to humans from animals. If a zoonotic agent is discovered in a human being before detected in an animal, we have failed”

In fact, it is not even the first coronavirus spill-over of the last 20 years, as both SARS-CoV and MERS-CoV emerged in 2003 from civets and 2012 from camels respectively. Four other coronaviruses have been in wide circulation causing the common cold for a long time, and, other common coronaviruses regularly cause significant disease outbreaks in livestock and food animals.

Notwithstanding intense ongoing discovery efforts and substantial new knowledge, there is however still much to be learned about this new virus. Critically important information related to the coronavirus biology, genomics and the host immune response is lacking or incomplete. Mr. Valdivia emphasized “an urgent need for effective countermeasures, not least, for safe and effective vaccines that can elicit long-term immune protection”. However, he cautions that important lessons from the virology and vaccine development efforts for SARS-CoV-1 and other viruses should not be ignored in the rush to respond to COVID-19.  Orion have considered these issues in their own ongoing efforts to pioneer a new way to develop and manufacture universal combinatorial vaccines for SARS-CoV-2 and other coronavirus

Prior experience with SARS-CoV using a variety of different vaccine approaches was based on the spike-glycoprotein (S); the logic being that it is the viral protein which mediates host receptor binding and viral entry. Though the spike does elicit strong neutralizing antibodies with the potential to protect against infection, there are safety concerns. Some of SARS-CoV-1 vaccines induced Th2-type immunopathology with eosinophil infiltration in animal studies and, therefore highlight a risk that they could cause negative health outcomes through vaccine-associated enhancement of respiratory disease, VAERD.  Vaccine development efforts must consider the potential pitfalls, not least a predominant focus on use of the virus spike-glycoprotein (S), as the primary vaccine design target. Furthermore, low-potency vaccines could force the virus to mutate into new forms, and these could have altered host range, transmission dynamics or immune recognition rending once effective vaccines ineffective against newly emerged strains. The authors warn that shortcuts in the vaccine development and testing pipeline can lead to safety and efficacy issues and recommend the development and use of improved preclinical animal models that can better address these concerns early and thus contribute to ensure the efficacy and safety of vaccine candidates. They also discuss the anti-vax movement, which will seize on any missteps to damage the reputation of the vaccine industry.

SARS-Cov-2 is currently believed to be a natural spill-over event, probably from bats via a yet-unconfirmed intermediate host. The recent article published by Valdivia-Granda and Richt, points to regions of SARS-CoV-2 genome that could recombine with other coronaviruses including those of livestock or companion animals. If this occurs, it could lead to the emergence of new pathogens with increased host range, transmission dynamics, altered clinical outcome and could render vaccines and other countermeasures in development ineffective.