Abstract
Coronavirus disease 2019 (COVID-19) certainly sparked curiosity, concern, and fear around the globe as the pandemic facilitated a strain on health care delivery in many countries. The acute phase of the pandemic in 2020–2021 emphasized the readiness of global health organizations and governments to (1) disseminate and share health information, 1 (2) develop infectious models of a contagion, 2 (3) develop therapeutics to combat the illness, 3 and (4) implement policies to curtail infection.4,5 While many may say that failures occurred along the way in these areas, it did bring into focus how prepared we are to meet the challenge of the next pandemic.
In this context, a recent forum was held by the World Economic Forum (WEF) in Davos, Switzerland, to discuss preparedness for the next pandemic. This preparedness is now an objective of the World Health Organization (WHO) which has adopted the Disease X verbiage to further call for global preparedness. The WHO states that “Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease” (
Relative to Disease X is the list of pathogens as surveyed by the WHO that result in 90% lethality upon infection. This list includes Ebola (EBOV) and Marburg virus (MARV) among others that threaten public health due to recent outbreaks. 6 MARV and EBOV are negative-sense RNA viruses from the Filovirus family. 7 While not considered airborne viruses, Filoviruses are zoonotic, meaning they are/can be transmitted from animals to people. The reservoir host of MARV is the African fruit bat. Sound familiar.
Bats have been recognized as the natural reservoirs of a large variety of viruses, including coronaviruses 8 and are portrayed as a reservoir in the Movie Contagion that blurs between reality and fiction. Elements of the movie include the vulnerability of certain populations, the challenge between government officials and scientists, the impact on an economy, communication breakdowns or information withheld, and of course fear. Of course, the most important element of that movie was the frantic effort to develop a therapeutic to quell the tide of the pandemic. In the end, it's all about the therapeutic. So how long and what approach to take to be prepared?
As the anti-EBOV vaccine is already available and MARV and EBOV are from the same family, it may be possible to discover a vaccine for Marburg within a short time if the global leadership, regulators, and vaccine manufacturers are willing to do so. Since it hasn't been done yet, how realistic is objective. This is the crux of the WEF discussion that nations need to work together to be prepared. While focusing on Disease X perhaps focus should be on understanding why we haven't done enough for the present set of lethal viruses. MARV should be a proof of concept for working together.
But developing a therapeutic is easier said than done. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provided us with another glimpse of the receptor types of a virus. Angiotensin-converting enzyme 2 (ACE-2) is a complicated molecule sitting on the surface of a cell with many important functions which manifest in the infection process and pathophysiology of the disease. The receptor also gave us a reason for understanding the potential for vulnerabilities in a population. On the other hand, early target cells of filoviruses are monocytes, macrophages, and dendritic cells. Several cell surface receptors have been identified to mediate EBOV binding and internalization, including Phosphatidylserine (PS) receptors (TIM-1) and C-type lectin receptors (DC-SIGNR). Do these cell types segregate a target population?
SARS-2 mutations display a range of attributes from being highly contagious to not that bad. Variants can range from being susceptible to our present arsenal of therapeutics, but a variant might develop that facilitates escape from them. Vaccines against SARS-CoV-2 can reduce the risk of infection as well as severe disease among those with breakthrough infection. The spike protein does play key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection.
However, the emergence of BA.2.86 or Pirola in those already infected with previous variants suggest that acquired immunity to one variant doesn't transfer to another. So, in short, instead of preparing for an unknown, focus should be placed on lethal knowns and understanding that therapeutics are not always a given savior. Much is still to be learned about the knowns that require cooperation among many stakeholders and insight to the pathophysiology of a given virus to prevent a pandemic from those viruses already in existence.