• Scott Britton

Is Lasting Immunity to Novel Coronavirus Wishful Thinking?

Anyone who’s taken the slightest interest in biology will recognize the seemingly infinite diversity, shapes and mechanisms that are how life operates. Viruses are no exception. Some are RNA and a few proteins, others contain DNA and many proteins. Some types like Poliomyelitis are packaged in elaborate icosahedral capsids and have no envelope at all. Indeed viruses come in a mind boggling array of shapes and configurations. SARS-COV-19 is a virus that by now requires no introduction. Six months into the pandemic we are learning just how different and similar the characteristics are for this force of nature, compared to the other members of its family. Back in 2013 the infectious disease community hoped perhaps erroneously that SARS-1 produced durable C4 memory response in the adaptive immunity of survivors. But there really wasn’t any way to know that for sure given that the virus wasn’t successful in sustaining human to human transmission. We did have considerable data for two of the four other human to human coronaviruses but the news wasn’t encouraging. Those viruses are 229E (alpha coronavirus) and NL63 (alpha coronavirus).

They are known to have some undiscovered mechanism that allows them to circumvent the adaptive memory, T-cells and B-Cells, Igg and Iga, Adaptive memory is the second act of the immune system providing a specific response to an antigen quickly identified to mount an overwhelming attack against known invaders. This is the kind of useful information that serology tests can provide. A patient may be tested at the time he or she is experiencing symptoms. Coronavirus antibodies might be present in the blood at high levels. Several months later if the patient has built up memory and encounters the same antigen (part of and/or whole virus) they are expected to contain high levels of antibodies again given a second serology test. That wasn’t happening with the corona cold viruses. It is not unusual for someone to get a worse cold six months later than they had the first time round. This has been the proverbial elephant in the room. There is now anecdotal evidence that SARS-COV-19 is getting around our adaptive immune system somehow. What this means is that “herd immunity” may not even be possible with this virus.

I keep up with the observations of some of the top people in infectious disease because that is part of fulfilling my mission with Acid Mitigation Training Academy. Daniel Griffin MD, is Board Certified in Internal Medicine and Infectious Diseases As the Chief of Infectious Disease at ProHealthcare network. Dr. Griffin sees patients himself while concurrently overseeing 3,000 physicians spread across three neighboring states including New York. The doctor examined an undisclosed patient in March resulting in a positive serology test for SARS-COV-19, showing high antibody levels. (Just because antibodies are present doesn’t necessarily mean they are effectively “neutralizing” virus, think HIV). It is now July and the same patient returned last week with an even worse case of COVID-19 than he exhibited back in March. The patient's blood was again SERO tested for antibodies and this time the test came back with only low levels of antibodies for SARS-COV-19. This indicates poor memory response. We’re still in the first inning of the game and this case is anecdotal evidence, not yet confirmed by controlled studies. Then again, it isn’t the only known case where apparent reinfection occurred a few months later. The same thing was reported in Washington D.C. The same thing is happening all over the USA. We need to know how this is happening, how often and to whom?

Informed by knowledge of influenza, the other major respiratory virus that causes atypical pneumonia and death, Dr. Griffin worries that many doctors are counseling patients to let their guards down. Many doctors may believe that patients should have some immunity to the novel virus. Everyone, health care workers, scientific investigators, public health workers and people like myself in sanitation and want to believe that to be true. The alternative seems too horrible to contemplate.

But Dr. Griffin thinks we need to carefully consider this possibility. He might be right. People may not be as careful given such well-meaning but possibly incorrect guidance. It is important that physicians carefully assess what is known and what is unknown concerning this novel virus. Think of HIV, a person that tests positive for human immune deficiency virus does not develop immunity at any time, the progression of the disease is insidious and the syndrome it causes is latent. The HIV virus is able to work around the immune system, to take over t-cells, hide and destroy immune response over a long period of time.

The particular mechanisms involved in transcription and replication of HIV, (of the Retroviridae family) has been thoroughly studied and are believed to be very different than both Influenza and Coronafamily viruses. This brings us to the point, we really don’t know the mechanisms that this novel virus is using, not in even close to the way that we understand the other viruses that have been studied more extensively. We know that the virus has 32,000 base pairs but knowledge is lacking about what most of the proteins and enzymes it makes actually do, nor how they do it.

Past studies for the other infectious disease were performed in labs, using animal cells, nutrients and chemicals to learn different things about how the virus reacts to those stimuli. However, data is in itself also informative. Data can tell the investigator where he might need to look, how and at what. Data can be plugged into known formulas. For example, the results of patient serology tests can inform setting up controlled tests to isolate a certain protein and see what the virus does without that specific protein. Patient confidentiality is maintained of course, but vital details of a case can be passed anonymously and become a key parameter and a possibly a useful metric. It is tedious work how researchers learn.

One current problem that gives Brianne Baker, Professor of Biology at Drew University, a headache is that several states have followed CDC guidelines combining the positive results of serology tests and PCR tests. The consensus among Professor Baker and colleagues is that those two tests tell us completely different things and that they each lose their individual value as indicators when thrown together in public health record keeping. It is kind of like putting a random unknown quantity of oil and water together in a 55-gallon drum. Sure you can weight that, you can discern the volume of it, but whatever properties that might have been actually useful are then obscured/ In combining them they essentially become immeasurable. It begs the question why would anyone want to do that? As far as I can tell, no scientist does. Brainne Baker asserts, (paraphrasing the professor) "only someone who wanted to appear to be doing a lot of testing, more testing than any other country, might find such jumbled information useful". But it is completely useless information to the people who matter most to our survival now. Of course I mean the scientists, and the mid-level workers of Public Health institutions who actually are doing their jobs trying to make sense of the data.

Source: This Week in Virology #617

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