Immunology and the Post-Pandemic World

New COVID-19 testing protocols will play a significant role during our transition out of the pandemic.

Are we all the way back to “normal” yet? Not quite. Yet thanks to some remarkable, expedited work from our scientific community, it’s safe to say that we are beginning to transition away from the depths of the COVID-19 pandemic.

Three types of CDC-recommended vaccines are now widely available to many Americans. At the time this article was written, over 64 million individuals around the US had received at least one dose of COVID-19 vaccine. Of those, over 33 million had received two doses. The vaccination topic is sure to continue dominating news headlines as more types are released, and to a greater portion of the population.

That said, it’s not quite as simple as “let’s get everyone vaccinated and reach herd immunity.” COVID-19 testing – which has been crucial in allowing us to manage the spread – will remain critically important going forward.

Even though daily testing totals have begun to decline from the January 2021 peak, there are still well over 1,000,000 tests being performed on a daily basis around the US. More importantly, however, the actual role that testing plays is beginning to shift from the micro (individual healthcare and transmission control) to the macro (restoring infrastructure and reaching herd immunity). The recent emergence of variant strains and still unclear impact certain vaccines will have only accentuates our ongoing reliance on testing.

How will the various types of COVID-19 test impact our “return to normalcy”?

The three primary types of available COVID-19 diagnostic test – molecular (PCR), antigen, and antibody (serology) – must be managed and deployed effectively by public health officials in order for us to seamlessly transition into a post-pandemic world. Here’s an overview of the impact each type may have.

Molecular (PCR) Testing

Molecular diagnostic PCR tests look for viral sequences of SARS-CoV-2 in a variety of sample types collected (nasopharyngeal, oropharyngeal, saliva, and sputum). Nucleic acids are extracted from the sample and amplified via polymerase chain reaction (PCR) or a similar process like isothermal amplification. The consensus is that these tests are generally the most reliable, and false positives are rare; however, being laboratory-based, they may have result turnaround times of 24 hours or longer.

PCR tests are great for accurately determining if an individual has a current SARS-CoV-2 infection. Some PCR tests even have the ability to identify the recently reported variant strains. Because of this, PCR will likely still make up the majority of SARS-CoV-2 tests performed over the short term – at least until all of our best vaccine options are rolled out on a broader scale and more is understood about variants.

For the longer term, PCR tests are not ideal mainly due to the longer result turnaround time. If we want to return to our normal way of life – one where we’re able to safely gather in crowds again – we’ll need to be able to quickly determine if an individual has COVID-19 and is at risk of spreading the infection to the rest of the crowd.

For this reason (and due to their higher cost), current PCR testing technologies aren’t well-suited as on-site rapid testing tools that will help us return to normalcy. We’ll need to supplement they way they are currently utilized with an additional immunological approach to testing.

Antigen Testing

Antigen tests are immunoassays that detect proteins or glycans, such as the spike proteins found on the surface of the SARS-CoV-2 virus. These antigens are part of an individual’s immunological (antibody) response; they send a signal to cells to start making antibodies. Like molecular tests, antigen tests are used to determine if a person has an active infection, albeit perhaps less accurately. False negatives tend to occur more often than with molecular.

But unlike molecular/PCR tests, they work very quickly – utilizing a similar technology to pregnancy tests (lateral flow) that can deliver negative results in roughly 15 minutes or less. They are also relatively low cost. The combination of these two factors makes antigen tests more scalable and more suited for rapid testing than the traditional laboratory performed test types and therefore likely more suitable for testing in the community and in remote regions.

This could also make antigen tests more amenable to point-of-care use – i.e. at smaller formal gatherings and events. “Rapid tests are better utilized for direct testing populations which require a rapid response, versus for example testing an entire school, which might be best done via PCR,” suggests Carl Hilliker, PhD, Director of Molecular Diagnostics Business Development at Thomas Scientific.

Germany, for one, is taking advantage of this scalability by granting special approval to seven COVID-19 rapid antigen tests for at-home use just last week. If deployed properly going forward here in the US, antigen tests could be a prominent catalyst in getting people back out into the public and reinvigorating our small business economy.

Antibody (Serology) Testing

Whereas the previous two are great for identifying current infection, serology tests look specifically for antibodies against SARS-CoV-2 to determine if there was a past infection. A sample from the patient is tested to determine if antibodies are present, which are critical for the body to fight off an infection. In certain cases, they can also determine the recency of when the illness occurred by evaluating IgG and IgM antibodies.

It’s important to note that a negative antibody test doesn’t necessarily mean that an infection isn’t currently present, which is largely why their use in the outbreak control and individual healthcare realms has been limited. The CDC also recently suggested that antibody testing is not ready to be used as a post-vaccine immunity assessor due to the unknowns surrounding different vaccines and variants.

This aside, antibody testing is where the future lies when it comes to transitioning into a post-pandemic world. They carry a ton of potential in terms of COVID-19 immunological research and public health as they have the potential to clarify an individual’s immune status.

Strides are actually already being made, especially in the area of rapid point-of-care antibody tests – which can provide results in just 15 minutes. This could very well open the door for breakthroughs in areas like workforce testing (determining which employees have high enough levels of antibodies to return to the office, etc.).

Still, a few key questions must be answered first before we can move forward optimally. “As we move into summer and more are immunized or positive & generating antibodies, the key will be how long you maintain protein spikes from a vaccine or maintain your body’s natural immunology,” stated Hilliker. “There will be a mix of antibody levels in the population as it relates to herd immunity, based on if they had been infected with the virus, or generated antibodies from the vaccine and how long those antibodies last, and the efficacy on the different strains will be looked at by many researchers.”

Other lingering issues of interest include:

  • Are antibodies present for longer with certain types of vaccine? Will the Johnson & Johnson vaccine provide the same level of immunity as Moderna’s?
  • Do all vaccines also give a person immunity to SARS-CoV-2 variants? (Believed to be true, but there’s nothing published yet)
  • What type of federal guidelines will be established for antibody levels? How many antibodies will one need, for instance, to be able to work without a mask on or go to a movie?

The scientific community is working tirelessly on solutions that will continue moving us down the path toward a post-pandemic world. Getting there safely and efficiently will likely call for a combined strategy that leverages all aforementioned testing types, along with continued vaccine advancement.

Special thanks to our Thomas Scientific Molecular Diagnostics experts for collaboration on this article.

 

Discover the Products Below to Streamline Your Post-COVID Molecular Diagnostics Workflow:

References

  1. CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccinations
  2. US Daily Tests | The COVID Tracking Project. https://covidtracking.com/data/charts/us-daily-tests
  3. Interim Clinical Considerations for Use of COVID-19 Vaccines. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
  4. CDC study says Abbott’s rapid COVID-19 antigen test may miss two-thirds of asymptomatic cases. https://www.fiercebiotech.com/medtech/cdc-study-says-abbott-s-rapid-covid-19-antigen-test-may-miss-two-thirds-asymptomatic-cases
  5. German Stores to Begin Selling COVID-19 Rapid Antigen Tests for Home Use. https://www.360dx.com/point-care-testing/german-stores-begin-selling-covid-19-rapid-antigen-tests-home-use#.YEt14Z1KiUl
  6. COVID-19 Testing: Molecular, Antigen, and Antibody Tests Explained. https://www.dshs.state.tx.us/coronavirus/docs/COVID19-TestingExplained.pdf
  7. Interim Guidance for Antigen Testing for SARS-CoV-2. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html
  8. Which test is best for COVID-19? Harvard Health Blog. https://www.health.harvard.edu/blog/which-test-is-best-for-covid-19-2020081020734
  9. The Role of Antigen Testing in the COVID-19 Pandemic. https://diagnostics.roche.com/us/en/roche-blog/the-role-of-antigen-testing-in-the-covid-19-pandemic.html
  10. Serology tests for COVID-19. https://www.centerforhealthsecurity.org/covid-19TestingToolkit/serology/Serology-based-tests-for-COVID-19.html
  11. FDA grants EUA for RapCov rapid COVID-19 antibody test. https://www.massdevice.com/fda-grants-eua-for-rapcov-rapid-covid-19-antibody-test/

 

For more on COVID-19, also read:

What is the role of HMGB1 in the immune response to COVID-19?

[CHECKLIST] The Comprehensive Guide to for COVID-19 Testing

Top Five Burning Questions Surrounding Proteinase K Use in COVID-19 Research

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