By Zania Stamataki
About nine months ago – as we now all know – a new coronavirus jumped to humans, causing a complex respiratory disease called Covid-19. The virus breezed through the planet with ease, hitching a ride on mostly unsuspecting carriers during the first months of infection.
Scientists quickly realised that they were dealing with a new pathogen, and they warned the World Health Organization. The clues: severe flu-like symptoms that resulted in higher than usual mortality, particularly in vulnerable groups.
The new coronavirus spreads via secretions from our mouth and nose, but it took us far too long to implement face coverings to reduce transmission. What did we know from the start? Coronavirus gains entry through our eyes, nose or mouth, and we can protect ourselves by washing our hands with soap and keeping our distance from people who may be contagious but without symptoms, or who subsequently develop symptoms.
The first thing that baffled us was the series of organs affected in Covid-19, beyond the lungs. Symptoms range from mild to severe, and their impact is seen from brain to toes.
The Covid Symptom Study app holds data from more than 4 million users in the US, the UK and Sweden, and suggests that there are six different types of Covid. We still cannot predict who will develop severe disease symptoms that lead to fatality, so even children, who were considered safe earlier this year, have now presented at random with rare but severe disease.
The question remains, for researchers and everyone else, is anyone safe?
To answer this, we need to look at how our immune system eliminates the virus. In itself, that reveals a hugely important positive concept: unlike some viruses that turn us into lifelong carriers (remember herpes, or HIV?), we can actually eliminate this coronavirus. For most of us it takes about two weeks. You have heard that immunology is complicated; here’s simply what we know so far.
Our bodies contain different types of defences, some evolved for speed, others for accuracy. Speedy defences deployed minutes after infection are part of the body’s innate immune system, and are powerful enough to control many pathogens. In researching Covid-19, scientists worried that if these were sufficient to control coronavirus, we would risk having no protection from reinfection. This is because rapid defences do not refine themselves to be more potent after the first infection, and they would be expected to mobilise in the same way when we become exposed to the same virus after recovery, suffering the same symptoms in the process.
Reinfection would fuel continuous transmission and extinguish hopes of herd immunity, which relies on the majority of the population becoming resistant to infection, to reduce the risk of transmission to vulnerable groups with poor defences. Thankfully, despite nearly 22 million recorded infections around the world, there is still no strong evidence of reinfection.
As months went by, some patients that cleared the virus started to report lingering symptoms. From brain fog to debilitating fatigue, heart damage to persistent muscle and joint pains, we recognise that some of us risk having “long Covid”, with a profound potential impact for our health and public health services. Protective immunity is critical to prevent disease.
The slower part of the immune system that has evolved for accuracy takes about seven days to kick off, and comprises B cells and T cells. These clever cells not only recognise that we’re suffering a virus infection, they are also able to pinpoint exactly which virus. How can they predict unknown threats? They can’t, so we have hordes of them patrolling our bodies with random recognition abilities for different parts of different germs.
If a lucky B cell recognises a virus, an activation cascade takes place that clones it into thousands of copies of itself and turns it into an antibody-producing workshop. This takes days, but antibodies and memory-type B cells persist after the virus is gone, so they can react rapidly if needed again.
Immunologists detected antibodies in the majority of people with confirmed Covid-19, but were unsure how long they would last for this virus. Studies showing that the early antibodies waned a few months after infection raised concerns for protective immunity. It is quite normal for early antibodies to dip a few months after infection. Remember, memory B cells are still left behind, ready to pounce if needed.
Other alarming research revealed a lack of antibodies in some patients who recovered. Some worried that this may mean lack of protection, or that vaccines were doomed to fail. Immunologists swiftly dispelled these myths, explaining that T-cell immunity can build independently of antibodies, and that vaccination can give rise to potent antibodies even if natural infection doesn’t.
Antibodies are Y-shaped molecules that use the two tips of the Y to stick to germs, but their other end is also important. The trunk of the antibody is recognised by immune cells that gobble up the antibody-germ complex, break it down into pieces and present it on their surface to activate T cells. They also release communication molecules to drive inflammation – and this can boost antiviral immunity, but may also cause collateral damage to tissues.
Patients with severe Covid-19 have higher antibody counts, and given the pro-inflammatory role of antibodies, there were concerns for antibody-dependent enhancement of the disease. We now appreciate that animals and humans given antibodies as therapy do not show disease enhancement. This is great news for antibody-based vaccination and therapeutic antibody treatments.
T cells drive antiviral responses and kill infected cells, and they also leave memory cells behind. They are more difficult to test than antibodies, but T cell tests are in development for broader use. T cells in coronavirus infections may persist longer than antibodies. Many of us also have pre-existing specific T cells, likely remnants from previous coronavirus infections that cause seasonal colds. This could explain why some get away with mild infection.
There is still much to learn about the new coronavirus, particularly how it causes severe disease and how we can prevent this. As the first data from global vaccine trials emerge, the hallmarks of protective immunity, both antibodies and T cells, are there. We now need to understand how our antibody and T cell measurements correlate with protection, are they of sufficient quality and how much is enough? As vaccine volunteers are exposed to the virus during the pandemic, we gather data to answer these critical questions.
The good news? Covid-19 may have surprised us with the wide range of disease symptoms and lingering effects on our bodies, but we have learned that our immune system is taking all the right steps for elimination. This coronavirus grows so easily in the lab that scientists are progressing fast to understand its biology and develop new antiviral therapies. In the meantime, we can all do our best to avoid getting infected and prevent transmission.
Zania Stamataki is a senior lecturer in viral immunology at the Institute for Immunology and Immunotherapy, University of Birmingham
Credit: The Guardian