Loft of an Eldritch Metaphor

Immunology // COVID-19 on Clubhouse

Posted on 20 Feb 2021

It started with a tweet

covid19 first tweet

And then, Arthur Yeow later replied “We can always start one”, and that was how I got here.

I did not expect to get serious about running my own Clubhouse session talking about viral immunology of COVID-19. Few hours later after talking and planning with Arthur and Yoong Khean, the date and time was then set to Saturday, 20 Feb 2021, 7:00 AM US Eastern Time (8:00 PM MY time, same day).

covid19 clubhouse announcement tweet

And then on the day of the show itself, I was also joined by Duncan Ng on the main speaker panel. Also, I was joined by Syikin Yunus (MD) and Isaac Tan (MD).

This page is a show note, the one you would usually see on a podcast episode release page.

The planning

Letting me to rein free would be a mistake. I thought it would be great if I could collect questions first so I could do a little bit of homework. This does not mean I won’t be accepting questions. In fact, I love questions, and I planned to have it run as casually as possible.

As for the theme, it would mostly cover the human immune response to SARS-CoV-2 infection. This would include the following sub-topics:

  1. Innate and adaptive immune response to respiratory viral infection.
  2. Antibody response against SARS-CoV-2.
  3. Generation of immunological memory against viral infection.
  4. Durability of immunological memory.
  5. Viral variants and implications to immunity.

I must say, by no means I am an expert in the following sub-topics, but I know enough to be able to say something about them comfortably, and I do know the boundaries of my knowledge in each of them.

Key points for select sub-topics

Few key points that I had prepared in advanced.

How come the development period for SARS-CoV-2 vaccine is so fast?

There are 2 main reasons, from biological standpoint, that I could think of.

First, SARS-CoV-2 is not the first human coronavirus. Going back into the history of coronavirus biology, the very first coronavirus characterized was avian infectious bronchitis virus (IBV) back in 1931. This virus infects birds.

The first description of human coronaviruses dated back in 1966 and 1967. Both viruses were identified as HCoV-229E and HCoV-OC43, respectively. Fast forward a few decades later, SARS-CoV emerged and caused an outbreak in 2003. About 8,000 individuals were infected, roughly 800 were dead. SARS-CoV (2003) was very scary, and people started designing vaccine against for it. It did not go far because SARS-CoV (2003) did not circulate in human. You just cannot get to human trials if the bug does not infect human anymore.

Fast forward in 2012, another human coronavirus made an appearance, the MERS-CoV. This corona was even scarier with a lot higher mortality rate of more than 30%. The interest in generating vaccine against coronavirus was renewed, and breakthroughs were made. Between 2012 and 2019, mRNA vaccine platform was under development. Also between 2012 and 2019, scientists made a number of discoveries on how to “stabilize” the primary vaccine target, the coronaviral spike glycoprotein, simply “the spike”. Stabilization of the spike makes the vaccine much more efficacious (immunogenic).

Then, December 2019 happened. Few weeks later on January 10th, the full sequence of the SARS-CoV-2 virus was published online, designated as the Wuhan-Hu-1. Days after the release of this sequence, labs around the world started working to make the vaccine based on the Wuhan-Hu-1 genomic template. Dr. Barney Graham has a wonderful thread on this, day-by-day, on the design of the Moderna’s COVID-19 mRNA vaccine.

So, bottom line, we do know SARS-CoV-2 based on other coronaviruses that had infected human.

Reason number 2, given that it has spread globally like a wildfire, it is relatively easier to conduct clinical trials. This was not possible with SARS-CoV (2003), the outbreak died within few months. This was not possible with MERS-CoV, the frequency of outbreak is just too sporadic.

And then you might ask “what about vaccine for HIV, and dengue?” Well, that’s… difficult. There is actually a vaccine for dengue, but there are some safety concerns. After all, flavivirus family (Zika and Dengue) is just difficult to deal with, something to do with ADE/OAS (not covered here). There have been a lot of vaccine trials for HIV, but the efficacy has not been satisfactory (33% the highest from RV144 trial). Why? I would like to talk about this, but it would get too long. In summary, HIV and dengue are the kind of viruses that are very challenging to make vaccine against. Coronaviruses, on the other hand (so far), not as challenging.

In other words, not all viruses are the same. Some are much more difficult to work with.

If I am taking immunosuppressant or on a chemotherapy, should I be taking COVID vaccine?

It… depends. I am an immunologist, so my opinion does not constitute medical advice. It is actually really challenging to answer this question, unless we know the specifics of the medication. On the other hand, I prefer not to know the specifics of your health information because it feels a little personal, so… here we go.

The default answer is almost always “yes, you should plan to get the vaccine, and please talk to your doctor”. That being said, I am aware of a study to which members of my lab participated looking at antibody response after Shringrix vaccination (for shingles, a.k.a varicella zoster) in cohort of patients with lymphoma (CLL and LPL) on BTK inhibitor medication. The outcome of this clinical trial? Strong specific humoral antibody response post-vaccination, and also strong cellular CD4+ T cell response, despite being on the BTK inhibitor.

With the COVID-19 vaccine rollouts running globally, I am pretty sure there are on-going clinical studies looking in specific human cohorts with specific health situations. We will know more in the coming few weeks or few months.

How does the vaccine work?

Hah! Where do I start? It would be really unsatisfying to simply explain it here, so I am going to wait until I have enough time to whip up a nice explainer about vaccine immunology.

Pinky promise!

If I was infected, should I still get the vaccine?

Default answer: yes!

But, here is another question: should you get both doses?

For the past few weeks, there have been discussions on this, and a few publications (pre-print) have been published regarding this. One of those publications was authored by a scientist that I am familiar with: Florian Krammer of Mt. Sinai, New York.

The answer? If you got infected before, a single vaccine dose is the current consensus.

But “why?”, you asked?

The infection could be counted as the “first dose”, and your first vaccine dose is your “booster dose”.

Closing words

Mostly it was fine, the Clubhouse session on COVID-19 immunology.

Might do it again in the future, I think.