Defeating COVID-19 and countering future pandemics
As we enter the fourth consecutive quarter of the coronavirus pandemic — which has brought with it over one million deaths and 40 million infected people worldwide – COVID-19 fatigue has spread nearly as rapidly as the virus itself.
While people will invariably grow weary, the virus never tires. In the United States, the absence of an organized national strategy has left us with a patchwork of responses that vary in effectiveness from state-to-state. Throughout the country, testing, coupled with contact tracing, is woefully under-deployed, allowing the virus an opportunity to fight well above its weight class. But there is positive news in the battle against COVID-19, stemming from an unprecedented collaborative effort by scientists around the world. Over 1,000 companies and academic institutions are hard at work developing vaccines or drugs to prevent or treat COVID-19. There are 3,352 clinical trials underway, and more than 180 diagnostic tests have already been approved for emergency use by the Food and Drug Administration.
We are clearly entering a different phase in the COVID-19 pandemic — one in which we can stop playing only defense and instead go on the offensive. Vaccines and new antiviral drugs, including combinations of antibodies that can neutralize SARS-CoV-2, the virus responsible for COVID-19, are just around the corner. For example, we now know that this virus devotes over one third of its genetic material to suppressing the human body’s interferon antiviral response; overcoming this suppression by treating patients with type I and III interferons is showing great promise. There is also optimism about the potential of antiviral drugs, which prevent the virus from multiplying. However, one of the shortcomings of one antiviral drug, remdesivir, is that it must be given intravenously, which effectively limits its use to hospitalized patients. By the time a patient is hospitalized, they may have already transitioned from the remdesivir-responsive viral replication phase of disease into the second phase driven by an overly zealous inflammatory response by the infected party. In this setting, dexamethasone, a powerful, inexpensive, and readily available steroid, can save lives. However, developing antivirals that can be delivered early in the course of infection, when the virus is in control, will be key to suppressing the pandemic. Aerosolized versions of remdesivir that could be inhaled might be one answer, but more are needed. Of note, the most exciting new class of antiviral therapeutics on the horizon is SARS-CoV-2 neutralizing monoclonal antibodies, which I suspect, will become a mainstay of early treatment.
Vaccines and new antiviral drugs, including combinations of antibodies that can neutralize SARS-CoV-2, the virus responsible for COVID-19, are just around the corner.
Safe and effective SARS-CoV-2 vaccines are our best hope to “break the back” of COVID-19. Achieving herd immunity around the world will require the manufacture and deployment of multiple vaccines. Fortunately, over 170 different vaccines are now in various stages of preclinical or clinical development. Four have reached final phase III clinical trials. It is critical that these clinical trials are taken to completion — even if the vaccine is shown to be effective before the full trial is complete — to ensure safety of the vaccine. Deployment of an effective, but ultimately unsafe, vaccine would be catastrophic, as it would undermine public confidence in the entire vaccine development approach. Moreover, despite the proven effectiveness of vaccines, as in the eradication of diseases such as smallpox and polio, public concerns regarding vaccination programs including that of COVID-19 must be addressed through improved education and communication campaigns.
The current situation has revealed how poorly prepared we are to deal with pandemics, and we only need look at the history of the coronaviruses to realize that more pandemics are in store. Three major pathogenic coronavirus transmissions have occurred in the last 18 years—SARS, MERS, and COVID-19. Hundreds more coronaviruses and other virus families are circulating in animal hosts and are poised for transmission to humans. Such “zoonoses” — diseases transmissible from animal to humans — represent three-quarters of the new human diseases that have appeared in the last 10 years.
The current situation has revealed how poorly prepared we are to deal with pandemics, and we only need look at the history of the coronaviruses to realize that more pandemics are in store.
Two key strategies that can be implemented now include strengthening disease surveillance and developing treatments that are active against a broad range of viruses. In terms of surveillance, changes in land use and encroachment on wildlife preserves have been linked to zoonotic disease outbreaks. This interface needs to be better regulated and managed. Clinics should be established near these interfaces and geared towards looking for early signs of pathogen-induced disease, including those displayed in domesticated animals. Wider mapping of viruses that exist in animal populations, particularly bats, should be promoted. Mobile phone-based disease surveillance should be more broadly utilized. This could be a powerful approach — a joint study between Google and the CDC to track influenza outbreaks based on Google search queries accurately estimated the weekly influenza activity across the United States with a reporting lag of only one day. GPS tracking, credit card usage, and other measures can also be used to track the effectiveness of isolation protocols and disease spread.
The identification of therapeutics that are effective against a broad range of viruses would allow us to have something ready in our drug arsenal when a new virus emerges. One approach to this is to have a better understanding of existing treatments. For example, it has previously been shown that the oral polio vaccine provides a broader spectrum of protection than anticipated. Specifically, it appears to limit influenza viral infections, to accelerate recovery from herpes simplex virus infections, and to control an unrelated acute poliomyelitis-like disease. Better defining the underlying immune mechanisms by which such vaccines produce unexpected benefit against unrelated viruses should be a priority, so that these features can be engineered into newly developed treatments. We must remember that viruses are simple, non-living organisms that must infect a host in order to survive. Understanding this process could yield new, broadly-applicable therapeutic strategies that are effective against many different types of viruses. Early investment in such strategies should help us “armor up” for the next pandemic, whenever it may come. Although clearly predicted, the COVID-19 pandemic has brought the world to a near complete stop, with economies suffering recessionary-like drops. We can, and must, do better with the next global infectious threat than we have with COVID-19. Our success will stem from more vigorous support of science, coupled with heightened pandemic preparedness.
