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why are antibodies critical in our battle against COVID-19?

coronavirus sars-cov-2-antibodiesProduction of antibodies are part of the body's defense mechanism. They help our immune systems fight off contagious disease and reinfection. This is the concept behind vaccinations.

A vaccination, such as a varicella vaccine for chickenpox or the annual flu shot, is composed of inactive or non-infectious parts of a virus that will trigger an immune response in our bodies. In doing so, this causes us to develop antibodies that help defend us against the disease when we are exposed to the real virus.

With some viruses, an initial infection causes our bodies to develop enough antibodies to give us natural, long-term immunity against a second bout of the same disease. This is why children who have had chickenpox (varicella-zoster virus), for example, don’t need to get the varicella vaccination for protection against reinfection.

Sometimes, however, our natural immune responses aren't enough to protect us against a disease. This is particularly true if we are exposed to high dose levels of a virus (a risk for healthcare workers), if the virus is particularly fast acting, or if our immune systems are compromised.

How do antibodies work?

The immune system produces several different types of disease-specific antibodies when it is fighting off a disease. Three of these antibodies, IgA, IgG and IgM, are of particular interest in COVID-19. IgA and IgM antibodies are part of the immune system's response to an initial viral attack, but these antibodies may fade away over time. If there is a second outbreak of the disease among the population months later, it is unlikely if survivors of the initial disease outbreak will retain enough IgA or IgM antibodies to ward off a second bout of COVID-19 illness.

However, IgG antibodies develop a bit later in the disease process, and scientists believe these antibodies can remain in your body longer (sometimes indefinitely) to (potentially) defend against reinfection in the future. So, while IgA and IgM antibodies are important to track, IgG antibodies are the ones scientists are focusing on to measure long-term immunity against COVID-19 illness. Unfortunately, a recent report suggests that 40% of asymptomatic carriers of SARS-CoV-2 may become seronegative for IgG antibodies within 2-3 months. More research in this area is needed.

How do you know if you have developed IgG antibodies against the SARS-CoV-2 virus that causes COVID-19 illness?

Upon infection, the body raises specific IgG antibodies to proteins specific to the SARS-CoV-2 virus. It is hoped that the presence of these antibodies is an indicator that an individual has developed a partial or full immunity—although this has not yet been proven. If development of raised IgG levels does indeed confer immunity, increasing numbers of healthcare providers and research scientists will be encouraging people to provide blood samples for serology studies that track and measure SARS-CoV-2 antibodies.

A blood sample for a serology test is different from a nasal or oral swab sample of mucus or saliva that is used for rapid testing of active COVID-19 illness. A blood sample provides the background information on how a person's immune system has responded to COVID-19 after they have recovered from it. Certain blood tests, for example, will reveal if IgG, IgA and IgM antibodies have developed.

Are rapid tests for antibodies different from in-lab validated tests for antibodies?

The at-home rapid tests for antibodies that you have heard about are based on lateral flow immunoassays similar to the technology used for at-home pregnancy tests. If a test is validated for capillary blood collection, you use a finger-stick method to place a drop of blood from your fingertip onto a testing strip in a plastic cartridge and wait for a “yes” or “no” result in the form of a line.

A “yes” line shows that you may be positive for antibodies, but you won’t necessarily know which type of antibody: IgG, IgA, or IgM. Some of these lateral flow rapid tests can distinguish between IgG, A or M, but many can't. Also, these types of tests have been shown to have higher rates of false negatives, and are less specific and less sensitive than in-lab testing using ELISA methods.

An ELISA-based test conducted in a lab allows for high throughput analysis and the capability to combine IgG, IgA and IgM antibodies in one well for a test that can potentially deliver results about specific antibodies. When you collect a blood sample at home using a Mitra® device, for example, and send it to a lab for ELISA-based antibody testing, your lab results can indicate specifically which antibodies you have developed: IgG, IgA or IgM.

Specific data about SARS-CoV-2 antibodies are critical for understanding immunity to COVID-19. This is why researchers at the National Institutes of Health (NIH) developed ELISA methods for testing both remote blood samples and serum in their serology studies for SARS-CoV-2 antibodies. The ELISA method developed by the NIH has very high specificity and sensitivity.

Many labs are now conducting SARS-CoV-2 antibody tests that use blood samples collected remotely with Mitra® microsampling devices from Neoteryx. These devices have been chosen by scientists and healthcare providers because they provide high-quality samples and can be used by anyone at home or on the go to self-collect small drops of blood from a fingertip using the finger-stick method.

Some healthcare systems are hosting “Drive-Thru Blood Collection for Antibody Testing” events where medical professionals use Mitra devices to collect blood samples from people in their cars. Other organizations, such as LGC, are shipping Mitra® Blood Collection Kits out to people at home so they can collect their own blood samples and send them directly to a testing lab through the regular mail.

Unlike other blood collection methods, virtually anyone can follow the simple instructions when using Mitra to easily collect a precise sample. A drop or two of capillary blood, absorbed onto the Mitra device tips, produces the precise volume of blood needed for scientific analysis. Shipped through the mail via regular post, Mitra microsamples are processed by lab researchers as dried blood specimens.

With Mitra at-home sampling, it isn’t necessary for people to risk exposure to contagions by visiting a blood draw center or providing tubes of whole blood. Mitra microsamples of dried blood, provide enough information for scientists to identify and measure IgG, IgA and IgM antibodies.

When should I get tested for SARS-CoV-2 antibodies?

Because of the extended time it takes for our immune systems to develop IgG antibodies, people who think they have contracted COVID-19 illness are encouraged to wait about 14 days after they suspect they had COVID-19 before collecting a blood sample that can be tested for antibodies. We know from other diseases caused by other coronaviruses, such as SARS and MERS, that certain antibodies can be detected in a person’s blood at least two years after they recovered from the illness.

However, do those antibodies ensure immunity? Will SARS-CoV-2 raised antibodies remain in the body that long, and will a COVID-19 exposure or illness help us develop enough antibodies for protection? These are questions scientists are still exploring, and blood testing the population will be key to finding the answers.

If my blood is positive for IgG, IgA and IgM antibodies, am I safe from catching COVID-19?

COVID-19 is such a new disease that, while scientists hope SARS-CoV-2 antibodies will provide protection, it is uncertain what level of protection they will provide. Scientists around the globe are spending countless hours researching this, and they have made some progress.

In fact, scientists at the University of Rochester and the National Institutes of Health (NIH) have used Mitra microsamples to develop serology study protocols that detect and measure SARS-CoV-2 raised antibodies with extremely high specificity based on the population that they were testing. This is good news after all the failed tests we have heard about that weren’t sensitive enough or didn’t furnish specific data. These new and more specific blood testing protocols show great promise, but scientists are still investigating how much immunity the SARS-CoV-2 antibodies may provide.

If you test positive for having developed IgG, IgM and/or IgA antibodies specific to SARS-CoV-2, you aren't necessarily immune to COVID-19, but your blood sample is of great value to science. Because your level of immunity is still unknown, you should continue following all the guidelines of social distancing, hand washing or sanitizing, and wearing a mask or face covering as outlined by the CDC, local governments, and health departments.

Eventually, if SARS-CoV-2 antibodies are proven to provide immunity against future infections, having your blood tested for these antibodies will provide valuable information for you, as well as for your entire community as they track development of a possible herd immunity. Information about antibodies and natural immunity is critical as we begin reopening businesses and schools, and gathering in groups to reboot the economy—a process that is important, but is happening before we have a working COVID-19 vaccine available.

Sources:

https://www.nature.com/articles/s41591-020-0965-6
https://www.nature.com/articles/d41586-020-00502-w
https://www.the-scientist.com/news-opinion/studies-report-rapid-loss-of-covid-19-antibodies-67650
https://www.cidrap.umn.edu/news-perspective/2020/06/chinese-study-antibodies-covid-19-patients-fade-quickly
https://www.nih.gov/news-events/news-releases/experts-identify-steps-expand-improve-antibody-tests-covid-19-response
https://www.medrxiv.org/content/10.1101/2020.05.21.20109280v1
https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-testing-sars-cov-2
https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests.html
https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html
https://www.lgcgroup.com/media/2284/lgc_dds_covid-19_assay_update_22jun2020.pdf
https://www.labcorp.com/tests/164055/sars-cov-2-antibody-igg
https://vidacheck.com/why-vidacheck/
https://www.the-scientist.com/news-opinion/what-do-antibody-tests-for-sars-cov-2-tell-us-about-immunity--67425
https://www.sciencealert.com/does-the-amount-of-covid-19-virus-you-are-exposed-to-determine-how-sick-you-ll-get
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342672/

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