Editor’s Note: This is the third installment in a series of regular columns on emerging science related to Covid-19 by Erin Bromage, an associate professor of biology at the University of Massachusetts Dartmouth. His research focuses on the evolution of the immune system and how animals defend themselves from infection. Follow him on Twitter @ErinBromage. The views expressed are his own. View more opinion articles on CNN.
This has been a rough week in the middle of a rough year.
After so many of us made serious sacrifices to stem the spread of the coronavirus, we let our guard down. What little leadership and communication we got from the White House in the early days of the pandemic have disappeared, and the tremendous gains the country made against the contagion after several weeks of lockdown have all but vanished. The US is now seeing a surge in new infections – with highs exceeding more than 55,000 new cases in a day last week – and hospital beds in certain hotspots are approaching capacity.
New York, New Jersey and Massachusetts fought hard-won battles in April and May, and the governors of these states, having learned their lesson, are now approaching their reopening plans by slowly and carefully assessing the situation before moving on to each new phase.
States like Texas, Arizona and Florida, on the other hand, dodged the brunt of the early outbreak, only to see a recent uptick in infections. It’s clear they failed to heed the lessons from the north and eased lockdown restrictions too quickly.
This type of learned response – or lack thereof – is similar to what we see in our individual immune systems when it comes to fighting viral infections.
When a pathogen enters the body, the immune system mobilizes a series of cells and proteins in what is called an “innate response” – a general, genetically hardwired immune response we are all born with. When faced with a low dose of virus, for example, this response can clear the pathogen before it establishes an infection and we never even know we were exposed. The downside is that our immune system does not learn how to respond more quickly or effectively if we are exposed to the same pathogen later on.
Our immune system learns from long, hard-fought battles.
When faced with a high dose of a new virus, the overwhelmed innate system calls in specialist fighter cells for backup in what is known as an “adaptive immune response.” These cells, called B-cells and T-cells, have receptors on their surface that can recognize the structures on pathogens. As pathogens have millions of unique structures, we need millions of unique B- and T-cells to recognize them. It is possible at the time of infection that we only have one B-cell or one T-cell in our body that recognizes the pathogen. But once these cells do recognize their target, amazing changes take place.
When B-cells and T-cells first recognize the virus they need to make copies of themselves. Each time they make a new cellular copy, the receptors that recognize the virus mutate slightly in the hope that the receptor recognizes the virus more effectively. This process of receptor-refinement and proliferation repeats, resulting in thousands of new B- and T-cells that can recognize the virus more strongly and precisely than the original cell starting the process.
After weeks of training, we have produced a large, highly trained fighting force ready to respond to the viral threat. Some of these cells jump straight into the fight (effector B- and T-cells), while other cells wait and watch (memory B- and T-cells).
Effector B-cells and T-cells play different roles in our protection. Effector B-cells produce antibodies that bind to and neutralize the virus – which stops it from invading our cells.
However, antibodies cannot neutralize a virus hidden inside a cell, where it can multiply until the body is overwhelmed. This is where killer T-cells come into play – they look for viral proteins within our cells and instruct these infected cells to die before signaling innate immune cells to eat the dying cell, thereby destroying the viral particles.
Assisting all of these defenses are the T-helper cells. The signals T-helper cells release instruct killer T-cells to activate, B-cells to mutate and proliferate and innate immune cells to clean up the mess. Together, all the cells and their proteins work as a team.
Once the viral threat has been eliminated, the effector B- and T-cells are often allowed to fade away, making space and resources available for other immune cells to respond to the next threat. However, the training these virus-fighting cells undergo doesn’t go to waste. The memory B- and T-cells are still slumbering inside us, and in some circumstances, they can persist for a lifetime, ready to jump back into the fight when the same pathogen reappears.
The adaptive immune cells take time to train and multiply, and the body may be in for a long battle when it is first exposed to a virus. Many people infected with the SARS-COV-2 virus that causes Covid-19 – especially those who are older with comorbidities – will not get through training their adaptive immune cells before succumbing to infection. This is why developing an effective vaccine is so important to combating this virus. With a vaccine we get to train our cells without the sickness that comes with natural infection.
In the next few months, scientists around the world will focus on understanding how our immune systems respond to the virus that causes Covid-19. What we learn will have major implications for how vaccines are designed, the cells they train and how long immunity might last.
Scientists are learning more about the antibody responses to the virus. Most people who are exposed to the virus and experience symptoms produce antibodies – but there are now some indications that they may not last for long.
But it does not necessarily mean people can be reinfected. Memory B-cells, when encountering the same virus, can change into effector B-cells, producing the neutralizing antibodies needed to neutralize the virus. How long memory B-cells persist following exposure to coronavirus is currently unknown.
It appears that successful clearance of the virus may lead to a pool of helper T-cells and killer T-cells that are ready to respond to future threats. In fact, the most recent evidence suggests that some people who are asymptomatically infected by the virus may only develop a T-cell response. So while these people might not have any antibodies, they may still be immune to the coronavirus.
The lack of an antibody response in some asymptomatic cases has profound implications for the current status of the pandemic in the US. Last week, the Centers for Disease Control and Prevention estimated that only 6% of Americans have been infected by coronavirus. This is a long way from the 60-80% we need for herd immunity. But the CDC estimate was based solely on studies accounting for antibodies, and not those who have T-cells that may make them immune to the virus.
That means the CDC may be undercounting the total number of Americans who are immune to the virus. If these T-cell responses prove to be protective, it means that we may be closer to herd immunity than the 6% statistic suggests.
That would be some good news in a terrible year.
Unravelling these immunological mysteries takes time. We are only six months into understanding how our body defends itself from this virus. The data is slowly emerging, and while there will be a continual refinement of our understanding of the immune processes that defend us, I am starting to see patterns in the data that give me hope that recovery from infection may lead to sustained protection from reinfection.