Fearing for the worst, Sara hoped to make it out of the city in time. Everything was in chaos, and hundreds of people were attempting to leave the city before it was locked down. The virus had spread extensively, and the number of deaths was rising. She just wanted to be home with her family and this was the last flight out. She was standing nervously in the line. Far ahead, officials dressed in bio-suit were beaming some device into each person before they let them pass. If the machine beeped, the person was probably infected with the virus and was taken immediately into quarantine. 

     Even though this appears to be a typical scene from a zombie movie, this, in reality, represents a scene from real life two years ago, when our world succumbed to the SARS-CoV2 pandemic. Based on our experiences with the SARS-CoV2 pandemic and our futile attempts at preventing the global spread of this virus, I wonder- If we were to ever encounter a deadly virus, similar to the T virus from the Resident Evil movie series that turns people into zombies, will we be able to stop it from spreading and save humanity? 

     Stealing the following setup straight from a zombie virus movie, let’s assume that the officials have decided to lock down the entire city. Meanwhile, thousands of people gathered near the checkpoints attempt to leave the contamination zone, perhaps before the government decides to bomb down the whole area. Individuals who want to leave the contaminated site have to pass through checkpoints where the authorities test whether they are infected with the virus.  In such a case, the officials need a device that accurately identifies infected people who can be isolated immediately. Meanwhile, the virus-negative people can leave the zone. Also, these devices must give quick results to be practical and save the lives of as many people as possible. We don’t want to be queuing for hours to leave a city under a zombie attack before our negative test results come in.  

    Based on the assumption that we might have a high fever when infected with a virus, temperature monitoring devices can be used for screening. The non-contact infrared thermometers (NCITs) can be used to measure our body temperature. How can a device identify our body temperature without even touching us? We know that we all are made up of atoms, the basic building block of all matter. Now, these atoms are constantly moving according to the surrounding temperature. The higher the temperature, the faster the movement will be. When these atoms move, they emit energy in the form of infrared radiation which cannot be seen with our eyes. However, similar to visible light, this infrared can be captured through a lens in the infrared thermometers and detected using a special detector. It takes only a few seconds for the device to record the body temperature. 

     NCITs are very convenient and easy to use. Many of us have come across one of these devices in airports, malls, or restaurants during the SARS-CoV2 pandemic. However, relying solely on these devices to identify virus-infected individuals based on their elevated body temperature is very risky. Temperature measurements alone may miss more than half of the infected people because not every infected person experiences a fever, similar to what we have seen with SARS-CoV2 infections. Further, some individuals might have taken fever-reducing drugs, making temperature measurements unreliable. In addition, it has been observed that exposure to emotional and stressful events can cause a psychogenic fever between 37 to 38°C. This means people who are not infected with a virus can be falsely identified as virus-positive. I think it is safe to say at this point that perhaps we better not use these devices in case of a zombie virus outbreak. What can then be used to accurately identify infected individuals? 

    We can detect the viral genetic material (DNA or RNA) from the patient samples like saliva or nasal or throat swabs. Looking for a tiny piece of viral DNA from a sample is similar to looking for a specific kind of needle from a massive stack of millions of needles. Fortunately, this seemingly impossible feat has been made possible with the help of a technique called polymerase chain reaction (PCR). The majority of the standard PCR assays require an additional sample processing step. Our nasal mucus sample, for example, contains other substances like proteins, salts, cells apart from the virus. Hence, to run a PCR assay, we need to eliminate all these other compounds except DNA/RNA. Then with the help of special proteins, when DNA or RNA is subjected to heating and cooling cycles, the amount of target sequence, in our case the viral sequence is amplified. With enough amplification, the PCR machine can detect the virus. With PCR, it is possible to amplify minute quantities of DNA or RNA into a thousand-fold. This makes it possible to detect even a tiny amount of viral genetic material in the sample.

     PCR-based tests are versatile and very accurate. For the past two years, most of us have taken multiple of these tests, mainly to be able to board a flight or just out of fear, every time we caught a common cold. During these times, we have noticed that it takes many hours from the sample collection until we get the results. This is because PCR-based tests require experienced personnel to process the samples and run the assays. This doesn’t look like an ideal situation during a zombie virus pandemic, where we need quick results. There have been several attempts to develop a PCR assay eliminating the need for an initial sample processing step or shortening the PCR run time. However, these newer PCR setups, which still fare poorly in accuracy and efficiency, are far from the routine application. We need a test as accurate as standard PCR and gives test results as fast as the NCITs when dealing with the zombie virus. 

     Instead of performing a PCR test, which detects a virus’s genetic material, we could also test for the presence of proteins on the virus’s surface. Like how different candies are packaged in unique wrappers, viruses contain differing protein coats that encase their genetic material. Detection of viral proteins is called an antigen test and uses lateral flow technology. The sample is first mixed in a solution that breaks the virus open and frees the viral proteins. This mixture is then added to a paper strip that contains a compound that binds to the viral proteins and this, in turn, results in a dark band on the paper strip. The best part about antigen tests is the possibility of getting results in a few minutes. But with antigen tests, there is a critical problem. Rapid antigen tests are intended primarily to detect high levels of the virus rather than its absence. Antigen tests give negative results when the viral quantity in our body is low. That means a person with low amounts of the virus may test negative. So, using this test at the checkpoints will not stop the spread of the zombie virus outside of the quarantined zone. And so, In this case, what other options do we have? 

   There is another set of tests called antibody tests. Rapid antibody tests require a blood sample. Instead of detecting the presence of the actual virus, the rapid test detects the presence of antibodies specific to the virus using the same paper-based detection as the antigen test. Antibodies are protective molecules, weapons of the cellular world, produced by our body to fight against pathogens. There are different kinds of antibodies produced at different stages of infection. When a virus enters our body, as the first line of defense, our body makes IgM antibodies. A positive IgM test indicates that the virus has recently infected us, and our body has started responding to the virus. However, developing a detectable antibody response for many infections occurs 5-7 days post-infection. So, if we are tested too soon after infection, our body has not had time to develop antibodies against this virus. This means even though we are infected, the IgM tests might be negative. Additionally, false-positive IgM results are common. This means even though our body doesn’t have IgM antibodies against the virus, the IgM test is positive. This is due to the possibility of cross-reactivity of IgM antibodies to other, closely related viruses or other interfering substances. Maybe we should stick with the PCR and antigen rapid tests compared to rapid antibody tests when dealing with the zombie virus.

     It looks like we have reached a dead-end in terms of finding the perfect test to save as many people as possible before the city is blown up and also in effectively stopping the spread of the zombie virus. Looking into the arsenal of viral infection detection tools that humanity has at its disposal, I would say these tests are good enough for our current pandemic needs, but maybe not good enough for a zombie apocalyptic future. We need a faster and more accurate diagnostic test for viral infection in case we are ever to face a deadly zombie virus. However, over 100 years ago, during the Influenza/Spanish flu pandemic (1918-20), we did not have any such tests or the technology to study viruses. Now almost a century later, during the SARS-CoV2 pandemic (2020-ongoing), we have viral diagnostics tests that give almost very accurate results in a few minutes. We have made significant advancements thanks to marvelous technologies like non-contact infrared thermometers (NCITs), polymerase chain reaction (PCR), and lateral flow assays. Perhaps one day, we will have more advanced tests to accurately identify deadly viruses and stop them from spreading.

Until then, if it were up to you, which test would you have used at the checkpoints to test people, if we had a zombie virus outbreak now? 

REFERENCES

1) How Do Infrared Thermometers Work? [WWW Document] (2020). URL https://www.omega.com/en-us/resources/infrared-thermometer-how-work

2)  Pană, B. C., Lopes, H., Furtunescu, F., Franco, D., Rapcea, A., Stanca, M., … & Coliţă, A. (2021). Real-World Evidence: The Low Validity of Temperature Screening for COVID-19 Triage. Frontiers in public health, 9, 891.

3)  Grodzinsky, E., & Levander, M. S. (2020). History of the Thermometer. In Understanding Fever and Body Temperature (pp. 23-35). Palgrave Macmillan, Cham.

4)  Oka, T. (2015). Psychogenic fever: how psychological stress affects body temperature in the clinical population. Temperature, 2(3), 368-378.

5)  Zhu, H., Zhang, H., Xu, Y., Laššáková, S., Korabečná, M., & Neužil, P. (2020). PCR past, present and future. BioTechniques, 69(4), 317-325.

6)  Wee, S. K., Sivalingam, S. P., & Yap, E. P. H. (2020). Rapid direct nucleic acid amplification test without RNA extraction for SARS-CoV-2 using a portable PCR thermocycler. Genes, 11(6), 664.

7)  Andryukov, B. G. (2020). Six decades of lateral flow immunoassay: from determining metabolic markers to diagnosing COVID-19. AIMS microbiology, 6(3), 280.