COVID-19 vs. Your Immune System — Antibody Testing

At a first glance, it doesn’t look like much.

Kind of like a ball of lint, with red Doritos and miniature Cheetos attached to it — if I’m being honest.

Of course, this is the infamous COVID-19; specifically, the CDC’s illustration of the novel coronavirus.

However, as the words “antibody testing” have entered the spotlight recently, it got scientists thinking… Perhaps those Dorito-looking proteins might actually be able to open the door to ramping up much-needed testing, vaccine development, and even potential treatments.

🔍 Getting Up Close & Personal With COVID-19

Coronaviruses fall under the general definition of viruses: non-living particles of genetic material (either DNA or RNA) wrapped in proteins. Particularly, viruses are not considered living things because they don’t fulfill the qualities of life, such as cellular composition, the ability to reproduce independently, etc.

That said, viruses are surprisingly goal-oriented — namely, their functions are, number one: to invade a host cell, and two: to start reproducing. In terms of step one, however, specific viruses are only able enter specific cells, termed the “lock and key” mechanism. In order for this entry to occur, the proteins on the surface of the virus must match with the proteins on the surfaces of host cells.

Now, with that background information out of the way, let’s zero in on COVID-19 itself. Coronaviridae viruses have a single-strand, positive-sense RNA, that is approximately 26 to 32 kilobases in length. SARS-CoV-2 (the novel coronavirus) shares 89% nucleotide identity with a bat SARS-like CoVZXC21, and 82% nucleotide identity with the human SARS-CoV — enough to identify it as a unique virus.

COVID-19 has several notable parts of its structure, including:

1. Grey surface = lipid membrane

This membrane surrounds the viral nucleus, and is made of genetic material. Its primary function is to bind other viral proteins together.

2. Orange bits (“Cheetos”) = membrane proteins

M, or membrane proteins, help to differentiate various viruses.

3. Red spikes (“Doritos”) = spike proteins

S, or spike proteins, allow the virus to attack human cells. In COVID-19, ACE-2 (protein on the cell surface) serves as an entry receptor. This helps the virus enter the body, bind to cells, and make copies of itself. S proteins also create the crown, or “corona,” effect around the nucleus. A spike mutation likely occurred in November 2019 which triggered transmission to humans.

4. Yellow parts = envelope proteins

E, or envelope proteins, allow the red spikes (more on this in a bit) to latch onto human cells. They are the smallest of the structural proteins, and play a role in viral replication — especially entry, assembly, and release.

🤒 Let’s Talk Antibodies

What are they?

Antibodies are the body’s biological method of recognizing its response to an infection so it can use the same response if infected again. Biologically, these are Y-shaped proteins produced by white blood cells to fight intruders, like viruses. People with antibodies in their blood have immune cells available to fight the virus, which lowers the risk of infection. Although there are many different kinds of antibodies, two to note are:

IgM antibodies:

Appear within days of infection, and fade away after the infection ends.

IgG antibodies:

Appear as the body clears the infection, offering longterm protection.

How antibody testing works

A COVID-19 antibody test would look for IgM and IgG antibodies, specific to this virus. To create the test, particular parts of the virus’ genetic material are isolated, which correspond to the spike proteins (i.e. where antibodies attach themselves). The body’s antibodies are uniquely shaped so that they can bind to the spikes and disable the virus.

Scientists have determined how to mimic the structure of the spike protein through lab-grown S proteins. Researchers isolate and inject specific parts of the viral RNA into other mammalian cells, causing these cells to grow with an outer shell similar to COVID-19. Then, these lab-grown S proteins are put into a special plate which immobilizes and concentrates them on the bottom.

To complete the test, the patient’s blood sample is taken and parts of the blood containing antibodies are isolated in a serum. The serum and lab-grown spike proteins are then added to a mixture on the special plate. If the liquid in the plate changes colour then, *voila*, the patient has COVID-19 antibodies.

☀️🌈 Sunshine and Rainbows : The Promise of Antibody Testing

Herd immunity

One slightly controversial aspect of antibody testing is the notion of herd immunity. Essentially, if enough people in a population get infected with COVID-19, and become immune to it, then the virus is no longer able to spread. As such, it will simply taper off, and allow life to return to normal.

Identifying the timeline of infection

Some tests are able to show how recently a patient was infected by distinguishing between types of antibodies in their sample. For example, the presence of more IgMs indicate a fairly recent infection.

Individual decision-making power

If antibody testing reveals that a person has COVID-19 antibodies, this person can now decide whether or not it is safe for them to rejoin the workforce, since they may be immune to the virus. This can be a game-changer, especially for frontline workers — like hospitals facing healthcare professional shortages — and restarting the economy.

Vaccine development and treatments

The synthetic S proteins developed for the antibody test may also help with vaccine development, by allowing the body to recognize the intruder and prepare a response pre-infection.

In addition, a treatment that’s been getting a lot of buzz is convalescent plasma. Basically, this involves injecting blood products containing antibodies to the virus from recovered patients into infected patients, in hopes that the antibodies will aid the immune response against the virus.

⛈️ Dark Clouds: Challenges of Antibody Testing

Accuracy

COVID-19 antibodies can appear very similar to other coronavirus antibodies, such as the common cold. This increases the risk of false positives or negatives, both of which are pretty bad in their own right. To measure accuracy of novel coronavirus antibody testing, two metrics have been established: sensitivity (i.e. the ability to detect viral antibodies at all) and specificity (i.e. the ability to distinguish these antibodies from other, similar ones).

Speed, cost and accessibility

The pandemic has already pushed some of the most vulnerable populations to the edges of society, like senior citizens. Even worse, there’s a desperate need for speed (literally) as different places grapple with testing backlogs. For example, in New York, the epicentre of the U.S.’ outbreak, only 34 per 1,000 people are being tested.

Unknowns of immunity

Since the novel coronavirus is, well, novel, there’s still a lot we don’t know. For one, how well are antibodies actually working? They might be able to produce a positive result, but actually offer little protection against the virus. Similarly, how many do you need to beat the virus? Immune status can vary widely from person to person (genetics, age, etc.), so it’s really hard to say. There’s also the potential of the virus staying harboured in the body and passed on to others, even if the individual has antibodies themselves.

Doing more harm than good?

It’s possible that antibodies might actually exacerbate the disease. Records show that hyperactive immune responses that damage healthy cells along with infected cells contributed to several deadly Covid-19 cases — and these responses likely involve antibodies.

💪 Conquering The Challenges: 3 Approaches

Learning from past products — MedMira

✔️ Speed, accessibility /❌ Accuracy is questionable

MedMira is known for its detection systems for other diseases. They repurposed their HIV detection system to detect COVID-19 in a 3-minute, point-of-care test. That said, this is based on their HIV model which had a wide range for accuracy, 100% in some studies, and only 80% in others.

Less is more — Abbott Laboratories

✔️ Accuracy, speed / ❌ Accessibility

Abbott elected to create a test that detects IgG antibodies only, as opposed to more types of antibodies. Lab instruments can run 100–200 tests / hour, with an incredible 100% sensitivity, and 99.5% specificity. Abbott’s downfalls lie in the accessibility of its tests, which must be administered by a healthcare professional on lab instruments i1000SR and i2000SR. This also poses issues of scalability and resource shortages in already overwhelmed medical systems.

Let’s just get it out there — PharmAct

✔️ Cost, accessibility / ❌ Accuracy

PharmAct was lauded as one of the first companies to create a COVID-19 antibody test. At only $40, the test was accessible and could be easily administered. However, the test hit a huge blow when it was denounced by German virologists after failing to catch ⅔ of cases in a German coronavirus hotspot.

💭 Parting Thoughts

In the midst of a global pandemic, there’s a lot that people — especially medical experts — don’t agree on. But, in a time like this, the one thing they do concede is that, it’s all hands on deck. Antibody testing could be a huge asset in the fight against COVID-19, so figuring out how to turn those dark clouds into more sunshine and rainbows is of utmost importance.

Key takeaways

  • When COVID-19’s spike proteins are detected in the body, they trigger an immune response involving antibodies
  • These antibodies can also be used to test for the virus
  • If successful, antibody testing can be a game-changer in tracking the timeline of infection, reboosting the economy, and developing vaccines and treatments
  • Challenges of antibody testing are centered around the many unknowns of the virus
  • Different companies have taken various approaches to antibody testing, but none have produced an infallible method yet

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