This week, I'm turning my column over to Jonathan Karn, PhD, Professor and Chair, Department of Molecular Biology and Microbiology, and Director, Case Center for AIDS Research. Many people would like to know more about coronavirus variants that are increasingly in the news across the globe. Jon has some answers—read on.
Stan
In 1890, the “Russian flu” swept through the globe, killing over one million people and leaving behind a range of perplexing symptoms. After the initial wave, there were recurrences from 1891 through early 1895. And then it all seemed to disappear.
Many virologists now believe that a coronavirus was responsible for that pandemic. In a faint virological echo, the illness is still with us in a weakened form as OC43, a ubiquitous common cold virus.
There are parallels from the 1890s outbreak to the current SARS-CoV-2 pandemic: the virus comes in waves, it will evolve and eventually become attenuated and endemic. Fortunately, today we have surprisingly potent vaccines available, effective tools to limit viral spread. However, the path forward will not be easy or straightforward.
Although coronaviruses are often very stable genetically, they will continue to evolve as they spread. As the number of cases increases globally, it follows that more infectious variants will arise, be identified and reported. In fact, the variants are already here—we just haven’t done a very good job of discovering them. Containing these variants will require careful global surveillance and rapid responses to new outbreaks, much as we currently do for flu.
The vaccines for SARS-CoV-2 are designed to elicit antibodies that block entry of the virus into cells. Technically, they target the receptor-binding domain of the viral spike protein that targets the ACE-2 receptor. Because of this protective mechanism, the genetic variants that are most concerning are in the spike protein. Fortunately, the vaccine-induced antibodies have so far proved effective at blocking all the known variants of the virus, including a South African variant that has multiple mutations in the spike protein. Furthermore, the vast majority of mutants in the spike will weaken interactions with the receptor and therefore lead to a less pathogenic or infectious virus.
However, in SARS-CoV-2, there is some additional genetic “wiggle room” for the virus to use alternative entry mechanisms (such as the recently discovered neuropilin receptor). Knowing that other receptors can exist means we have to watch for new variants that might require additional, more specific vaccine strategies and boosting.
Once a new and rapidly spreading virus arises, it is important to use epidemiological and clinical studies to determine whether it is more pathogenic, highly infectious but less pathogenic, or vaccine-resistant, as soon as possible. In the U.S., the weak infrastructure for monitoring new strains needs to be intensified, especially to incorporate sequence analyses of the circulating viruses.
Despite these important considerations, two factors mitigate against the concern that a highly infectious and pathogenic strain will overwhelm efforts to stop the pandemic. First, since there are cross-protective immune responses to coronaviruses, the existing vaccines will always be at least partially beneficial. That is one reason why everyone should get vaccinated as soon as the vaccines become available—not only to protect ourselves, family and friends, but to limit the opportunities for new variants to arise.
Second, the RNA vaccine platforms, such as the Moderna and Pfizer vaccines, are extremely flexible once the sequence of a new viral variant is obtained. As in the case of the original vaccines, new vaccines can be made in a matter of weeks by simply including the variant sequences in the mRNA design. This type of “cocktail approach” is used as a strategy for flu vaccination where both old and new strains are utilized in the annual design. The emergence of resistance against antiviral drugs, such as Remdesivir, is also less likely at a population level due to their current limited use. Unfortunately, creating new antibody drug cocktails as prophylactic agents would be a substantially longer and more complex process.
The research community at CWRU, with our long tradition in global health and the remarkable collaborations arising from the SARS-CoV-2 Task Force, will continue to play our part in developing a better understanding of this disease. Key questions we’re addressing are:
- How broad are the immune responses to SARS-CoV-2 vaccines against new variants?
- How long does immunological protection last?
- Are the new variants more infectious or pathogenic?
- The genome of coronaviruses is over 30 kB and encodes numerous proteins in addition to the spike, all of which are subject to variation. Are certain variants associated with different severe disease outcomes, such as cardiac or neurological consequences to infection?
Because of the risk of viral variation, there will be no getting back to “normal” in the short term. It’s a big world. Most people globally will not be vaccinated for years. And once viruses arise, they transit the world with alarming speed.
Everyone should continue to practice social distancing and good hygiene even after we are vaccinated, to limit virus spread and restrain opportunities for new variants to take hold in the U.S. until community incidence rates are vanishingly small.
Done vigilantly, we will not only vanquish SARS-CoV-2, but we will also reap the benefits of having far fewer cases of flu and colds.
Now, there’s a silver lining!
Jonathan