The Covid-19 Chronicles: Remembering an important lesson

A Song of Ice and Fire (ASOIAF) by George R.R. Martin is my favourite book series. Many may more readily recognise its television adaptation, Game of Thrones.

In the series adaptation, the saga ends with the Houses of the North, the Night’s Watch, the Vale, the free folk and the Dothraki uniting to fight the Great War against the White Walkers.

Although ASOIAF is known for being a long stretch of various Houses and Kingdoms constantly at war with each other, in times of real crisis, as one would be facing a multiplying army of undead who do not care about political alliances (or anything), unity suddenly becomes possible. Unless your name is Cersei Lannister.

This seems to be the case with Covid-19. In a time where science has been accused of operating in silos and disenfranchised in society, Covid-19 turns the tide with alliances, solidarity and interest in using science not only to fight the pandemic, but fight to survive its ramifications.

Given the scale of Covid-19, costing more than 200,000 lives in over 200 countries within months, unity may be the key to win this war against a battalion of viruses a million times smaller than the width of a strand of human hair.

The wars that we fight as human societies are in many ways similar to what happens on the molecular level, when our bodies are breached by foreign invaders like the the SARS-CoV-2, the virus that causes Covid-19.

There are multiple levels of defences, beginning first with physical barriers like our skin to prevent entry.

Once that is breached, the first line of defence, our innate immune system kicks in. This troop of cells use relatively crude methods to recognise foreign enemies, swallowing and digesting them whole, while sending alarm signals calling for back-up if they are unable to contain the breach.

This back-up comes in the form of more elite forces called the adaptive immune system, which are able to recognise invaders more specifically and comprise two main types of cells - B cells and T cells.

The former are known for its ability to produce antibodies to specifically recognise and neutralise the invaders, and the latter is known for enabling infected cells to commit suicide, along with the invaders they carry within. Together, these elite forces are the key to our ability to develop “immunity” to anything that has infected us previously.

Unlike the innate immune system, the adaptive immune system is able to remember previous invaders, by binding the unique molecules on the enemy, enabling them to effectively defend the body if they ever encounter similar invaders again.

This is why we can use vaccines to protect against disease. Trained to recognise an invader by introducing parts of the invader or a live weakened version in a vaccine; a process that mimics an infection will result in the former stimulating B cells to produce antibodies and the latter stimulating the T cells to remember and defend us against that specific invader in the future.

Using different approaches, researchers are working to develop a vaccine to train the immune system and protect humanity against Covid-19.

It took 42 years until we had a vaccine against measles, and the shortest time taken to develop a vaccine was 16 years for Hepatitis B.

Amazingly, we already have 18 vaccines in preclinical development, and five vaccines in phase 1 trials, ie being tested in humans, for Covid-19.

These candidates include DNA and RNA vaccines, a new approach yet approved for use in any human infectious disease.

While it is encouraging that there are many candidates, the complications that challenge these efforts are not trivial.

First, we do not understand whether being infected with SARS-CoV-2 results in protective immunity.

In some infections, the antibody responses are not long-lived and re-infection can occur after an extended period of time.

Whether reinfection results in the same severity of disease is unknown.

Reports of recovered patients having the virus at follow-up raises the sobering possibility that reinfection or reactivation is possible.

Second, the wrong type of vaccine might make things worse. A hallmark feature of Covid-19 is the damaging inflammation that happens due to a “cytokine storm” that becomes fatal in many people.

Cytokines are molecular signals which different immune cells produce, ie the artillery used in the war against invading viruses and bacteria.

Similar to the battles that see innocent civilians caught in crossfire between warring sides, overproduction of cytokines does not discriminate the enemy from the host, destroying what it is meant to protect.

Third, even if an effective vaccine is developed, issues of manufacturing, distribution, access and effectiveness for different groups of people are further challenges that need to be overcome in order to achieve “herd immunity”.

Only through herd immunity, ie having most of the population immune either from vaccination or surviving an infection, will we be able to eliminate Covid-19, like we were on track to do with measles.

Assuming, of course, that there are no problems of vaccine refusal as seen in the latter. Alas, although our immune system’s memory protects us, our human memory appears less reliable.

Regardless, for now, a vaccine against Covid-19 is what the world awaits with bated breath. For until an effective vaccine is found, the prospect of returning to life pre-Covid-19 may just be a fading memory.

Indeed, some things may change forever, perhaps for the better, even if we find a vaccine.

In ASOIAF, Arya, the girl who became a dueling machine wisely remembers, “Syrio says that every hurt is a lesson, and every lesson makes you better.”

While we wait for a vaccine, we can remember the war that constantly happens within us on a molecular level.

It is beautiful tragic war, a concerted effort filled with self-sacrifice for the sake of defending the territory.

We can remember in this war against Covid-19, the sacrifice of our frontliners who put themselves at risk to defend human lives and public health from Covid-19.

We can remember the many casualties of this war; those who lost their livelihoods, and those who may be collateral damage under indiscriminate orders of movement control.

It is now Ramadan. For Muslims, a time of remembrance and reflection.

May this hurt be a lesson we remember, one that we reflect on to make us all better.