The Solution to Coronavirus Variants: Vaccinate

There is a lot of understandable worry right now that “variants” of the coronavirus that causes COVID-19 may somehow elude the available vaccines and dash our hopes for an end to the pandemic. While concerns about variants are certainly warranted, right now we can say that the best approach to confronting them is to get everyone vaccinated as fast as possible and to increase U.S. surveillance for them.

         All available evidence suggests that the vaccines we now have are active in providing immunity to the viral variants. These variates—or mutated viruses–pose, as we will see, a particular threat to unvaccinated people because some of them are more easily transmitted and capable of causing more severe disease than the original coronavirus, which is called the “wild type” virus. So we must redouble all our efforts to convince every adult to get vaccinated as soon as eligible.

How Variants Form

         Let’s first explain what “variants” actually are. Remember that the COVID-19 virus, which is called SARS-CoV-2, is an RNA virus, meaning that its genetic information is contained in a single strand of RNA. That strand of DNA has about 30,000 bases that code for the virus’ 29 proteins. One of those proteins is the spike protein that forms those crown-like projections from the virus, or spikes, that have become familiar to us from images like the one provided here. The three currently available COVID-19 vaccines (Moderna/NIMH, Pfizer/BioNTech, Johnson and Johnson) and a fourth that may soon become available in the U.S. (Oxford/AstraZeneca) all target the spike protein.

The coronavirus that causes COVID-19 has the familiar spike proteins that emerge from the virus particle surface. It is the spike protein that current vaccines target (image: Shutterstock).

         When SARS-CoV-2 infects a person, it latches onto a specific receptor called the ACE2 receptor, that is present on various cells in the body, including the lungs and heart. This enables the virus to enter the cell. The viral RNA then hijacks the human cells’ protein manufacturing system to make new viral particles that then burst out of the human cell in order to infect other cells.

         To be able to make new virus particles, the virus’ RNA strand must be copied or replicated over and over again. Each time a copy is made, those nucleoside bases are assembled in the order needed to make a new viral RNA strand. Mistakes frequently occur, however, and an incorrect base is put into the sequence on the developing RNA strand. Coronaviruses have proteins that are quite efficient in clipping out those mistakes, which is why they actually mutate very slowly (unlike the virus that causes the flu). Nevertheless, sometimes an incorrect base remains in place. Most of the time, these mutations have no consequence, and the viral proteins are assembled in the usual, “wild type” way. Sometimes, however, the mutation does affect the structure of proteins, including the spike protein. This can result in several things: it can make the mutated virus incapable of further replication and it disappears or, ,more ominously, it can make the mutated virus particles able to cling more tightly to the ACE2 receptor, more easily transmitted from one person to the next, or less recognizable to neutralizing antibodies. By the rule of “survival of the fittest,” mutated viral variants that make the virus more “fit”—that is, more able to infect human cells—will ultimately predominate over less fit wild type virus.

The single strand of RNA that contains the instructions for making the coronavirus’ 29 proteins is itself composed of bases called nucleosides. A mistake that puts the wrong nucleoside in a spot on the RNA strand can lead to a mutation that makes the virus more easily transmitted or capable of causing more serious illness (image: Shutterstock).

Where We Stand Now with Variants

         There are three viral variants of particular concern right now, B.1.1.7 first identified in the U.K.; B.1.351 first seen in South Africa; and P.1 that seems to have emerged in Brazil. According to Anthony Fauci, about 30 percent of U.S. COVID-19 infections now involve the B.1.1.7 strain of virus. Each of these three mutated viral strains seems to transmit more readily than the wild type virus, but once again it appears that the available vaccines are able to generate sufficient neutralizing antibodies that recognize the variants’ spike proteins and at least prevent serious disease or death. The Johnson and Johnson vaccine, for example, was tested in both Brazil and South Africa where two of the variants were first seen and still protected people from getting seriously sick or dying.

         Another thing to remember is that neutralizing antibodies, which are produced by one type of immune cell called B lymphocytes, are not the only thing that vaccines stimulate to fight infection. T lymphocytes, which mutated viruses are less able to elude, are also stimulated by vaccines and form an important part of the immune response to viral infection. Right now, scientists know much less about the T cell response to SARS-CoV-2 than they do about the B cell response, but it is likely that T cell immunity plays an important role in vaccine protection against SARS-CoV-2.

         It would be fairly easy for the pharmaceutical companies that manufacture vaccines to quickly update them to cover variants. That might mean we will need booster shots at some point in the future. It is not clear yet whether that will be necessary.

         It is also important to note that viruses do not have an infinite number of possible mutations. As we mentioned earlier, most mutations in the RNA region that codes for the spike protein either have no consequences or render the virus unable to infect human cells. Mutated viral strains mainly arise in unvaccinated people whose immune system response is not robust enough to neutralize or kill enough viral particles, allowing the mutated strains to survive and be passed on to others.  The way to limit this process from occurring is to get everyone vaccinated.

         We cannot be complacent about variants. The U.S. has not been nearly as vigilant at sequencing virus to identify mutations as have other countries, and this needs to be fixed. It is not impossible that a mutation will occur at some point that renders virus resistant to the available vaccines and this would require more urgent development and administration of updated vaccines.

         We should not, however, think of mutations as an endless source of vaccine-resistant virus. “Over time,” writes Dhruv Khullar in the New Yorker, “SARS-CoV-2 is likely to become less lethal, not more.” For sure, the CDC needs to orchestrate a much wider surveillance of viral sequences to ensure we are not missing new strains that are more efficient at transmission or more lethal. The real urgency right now, however, is to get all of us vaccinated. That should dampen the threat posed by viral variants.

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