Laboratory tests for Covid variants is an important part of combatting the pandemic.
Dr. Rodney Rohde, a virologist and clinical laboratory expert, explores the challenges of detecting coronavirus variants.
My wife recently asked me this question: Does the first Covid-19 laboratory test you get say which virus variant has infected you? I thought to myself, what a wonderful question. I immediately began to wonder how many people really know what a virus variant is much less, how we can detect new viruses that are circulating in the United States or globally.
For medical laboratory and public health laboratory professionals, the answer to this question is well known: No, the test does not tell you which variant has infected you.
Typically, the first laboratory test conducted for a Covid-19 infection is either a rapid antigen test or a more precise (accurate) molecular test known as a polymerase chain reaction (PCR) test. The first test ordered for someone suspected of having a SARS-CoV2 virus infection is often conducted to tell us if one is positive or negative for a Covid-19 infection. To date, there are numerous emergency use authorized (EUA) and FDA approved tests available for Covid-19 testing.
However, what about those virus variants we all keep hearing about and seeing in the headlines? That is a different type of test and before we discuss those tests, it is important to understand how viruses mutate.
Virus mutations and variants
All viruses and other microbes are constantly changing, and this includes SARS-CoV-2, the virus that causes Covid-19. These genetic variations occur over time and can lead to the emergence of new variants that may have different characteristics. An analogy that I like to use with my family, friends and the public is to think about the game “telephone” that we have likely all played at some point in our lives. In this game, one person tells someone a story quietly in his or her ear. Then, this person tells another person quietly. This continues for several people. Finally, the last person tells the story aloud for all to hear. We all know what happens next. The story is related but usually different at the end of the game.
This is similar to what viruses do in nature. Viruses replicate all the time. As a virus replicates, its genes undergo random “copying errors” (i.e. genetic mutations). Over time, these genetic copying errors can, among other changes to the virus, lead to alterations in the virus’ surface proteins or antigens. When this occurs, new “stories” (virus variants) emerge that may seem related, but can be different.
How coronavirus variants impact tests and vaccines
These “mutations” may sound scary, but it is important to understand that many of these mutations are minor, and do not have an overall impact on how fast a virus spreads or potentially how severe a viral infection might be. In fact, some mutations could make a virus less infectious. However, sometimes these mutations can lead to problems for diagnostics and vaccines because when a virus changes how it can be detected (diagnostics) or how it appears to our immune system (vaccines / natural immunity); it could lead to false negatives on a test.
The United States lags behind at least 30 countries in terms of the sequencing it has done throughout the pandemic.
Similarly, these alterations in the virus can lead to a reduced ability of our immune system to detect or “see” the new version (variant) of a virus. In some cases when this occurs, it can be more difficult for our immune systems to protect us. Likewise, these virus changes or virus variants may become the dominant version circulating in the population and could reduce the effectiveness of current vaccines.
What has detecting variants taught researchers so far?
Public health experts have largely offered up reassurance that existing Covid-19 vaccines (Moderna, Pfizer, and Johnson and Johnson) work well against dominant variants. In a small real-world study by Israel's Tel Aviv University; however, the data suggests that the B.1.351 variant first discovered in South Africa may be able to evade the Pfizer vaccine. In this small study, there were approximately eight times as many cases involving the variant among 400 patients who had received two doses of the Pfizer vaccine 14+ days before compared to 400 unvaccinated patients. The report does state the study limitations of it being a small preprint study including only those who had already tested positive for Covid-19; also, the South Africa strain is far from dominant in Israel.
The Washington Post recently reports that a small fraction of the approximately 66 million fully-vaccinated Americans have experienced “breakthrough infections” and some have even required hospitalization. These infections are rare and only in the thousands. Experts stated that these breakthrough infections were in people who mounted poor and weakened immune responses to the vaccine such as the elderly with underlying health conditions.
How are virus changes detected in real time?
Currently there is no conclusive evidence that SARS-CoV-2 variants are leading breakthrough infections. However, how will we know if this is happening? An ongoing issue is the major gaps in U.S. virus sequencing data, which make it impossible to identify the variants (or strains) behind each Covid-19 case.
In a recent Nature article, it was reported that U.S. government supported laboratories have doubled the rate at which they are sequencing SARS-CoV-2 genomes over the past two months. Still, the number of genomes that the country shared in the online genome repository Global Initiative on Sharing All Influenza Data (GISAID), in March represented only 1.6% of its positive Covid-19 cases that month. Yet, the United States lags behind at least 30 countries in terms of the sequencing it has done throughout the pandemic.
Sequencing is a specialized laboratory test to detect specific genetic changes in a viral genome. It is the answer to my wife’s question about how we can tell which virus variant is causing a positive test. The first test is usually the one that tells a physician if you are positive with a Covid-19 infection. However, to understand which virus variant caused that infection, one must conduct a virus sequencing test or analysis to document the variant. In this way, our public health system can geographically map the transmission and prevalence of any new changes in breakthrough infections as well as which virus variant are dominating a particular area of the country.
Covid variants could potentially impact how effective vaccines are.
What is CDC doing to track SARS-CoV-2 variants?
Since November 2020, CDC regularly receives SARS-CoV-2 samples from state health departments and other public health agencies for sequencing, further characterization, and evaluation. On January 25, 2021, the National SARS-CoV-2 Strain Surveillance (NS3) system was scaled-up to process 750 samples per week. Notable strength of this system is the regular collection of numerous representative specimens from across the country and characterization of viruses beyond what sequencing alone can provide. Additionally, the CDC is also partnering with large commercial diagnostic labs and universities to increase sequencing capacity for surveillance of virus samples. The SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) is now available. The SPHERES collaboration includes scientists from clinical and public health laboratories, academic institutions, and the private sector. SPHERES will strengthen Covid-19 mitigation strategies.
Why is genomic surveillance important for public health?
According to the CDC, the ability to conduct routine surveillance for SARS-CoV-2 virus variants and other pathogens is critical to identify and characterize variant viruses—either new ones identified in the U.S. or those already identified abroad—and to investigate how variants impact Covid-19 disease severity and the effectiveness of vaccines and treatment.
Genomic surveillance allows public health authorities to detect if variants:
· spread more quickly in people
· cause either milder or more severe disease in people
· evade detection by specific diagnostic tests
· have decreased susceptibility to medical therapies with monoclonal antibodies
· evade natural or vaccine-induced immunity
Many of us in public health have long screamed that we are not taking the issue of public health funding seriously, including this very real problem of a lack in microbial sequencing capability and other initiatives to detect emerging and reemerging pathogens. President Joe Biden listed variant surveillance as a priority for his administration, and it was specified as a response measure that will receive some of the U.S. $19 billion in Covid-19 relief funds.
We welcome this potential funding initiative but now we must let the federal money flow faster and work towards correcting systemic problems in sharing samples and data to allow for the work to happen. These changes must also be looked at as important as our funding of the Department of Defense. Viruses and other microbes have killed more people than many wars as well as terrorism in this country and abroad.
Shouldn’t public health be as important as our overall military defense?
