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22 January, 2021

Human Immune Response to Covid-19:

What We Learned in 2020 and What to Expect in 2021

Dr. Jonathan D. Agnew

Faculty of Medicine

University of British Columbia

Medial staff distributing covid-19 vacci

The advent of COVID-19 marked a turning-point in the history of infectious disease.  The rapid spread of the virus and the herculean efforts by governments and businesses around the world to prevent or reduce its harm are unprecedented.  So, too, has been the rapid development and deployment of vaccines against the disease.  Since the only long-term solution to protect people from COVID-19 is vaccination, understanding what we learned about COVID-19 in 2020 and what we can expect in 2021 means looking at the science behind vaccination, and that requires an understanding of the human immune response to COVID-19.

The Immune System

The human body is protected against disease by the immune system, which is made up of several components that work together to maintain health and protect the body from cell changes, germs, and other harmful substances.

The immune system uses two main strategies to combat disease.  The body’s first line of defense during the early hours and days of exposure is through the innate immune system.  This system is not specific to a particular germ or substance, but rather is a generalized response of the body to any pathogen.  Like any good defense, the innate immune system begins with physical barriers—things like skin and mucus that coats the lining of the gut and lungs.  Other innate immune system responses, like inflammation and white blood cells, work to eliminate pathogens that can cause infection.  

The second strategy is the adaptive immune system.  Although slower to respond than the innate immune system, the adaptive immune system is highly evolved and complex.   It relies on two types of cells, B cells and T cells, to attack pathogens not yet destroyed by the innate immune system.  Their effectiveness derives from the ability to become specially tailored to the invader.  In other words, B and T cells can react to specific pathogens by developing antibodies and respond with a more targeted and powerful effect than the generic responses of the innate immune system.   

The Human Immune Response to Coronaviruses and COVID-19: What We Learned in 2020

COVID-19 was recognized early on as a coronavirus, so scientists quickly understood that, like all coronaviruses, it could manipulate the body’s immune response and evade the innate immune system.  It does so by first interfering with pattern recognition receptor signaling—the mechanism that alerts the immune system to a pathogenic infection.  Coronaviruses also interrupt the interferon pathway—a mechanism of the immune system that stops viruses from replicating.  By stopping this immune response, COVID-19 can continue to replicate freely in the body.  Ironically, the coronaviruses still trigger an inflammatory response, which when prolonged, damages the body’s healthy cells.  The result is a triple-whammy: COVID-19 fends off the immune system’s attempts to keep it from replicating, stops the body from signaling its presence, and still triggers an inflammatory response that damages healthy cells but not the virus itself.  

Coronaviruses live in humans and animals, and scientists tried since the emergence of the COVID-19 coronavirus in 2020 to determine its origins.  Although there is strong evidence that it originated in bats, it remains unknown how it was transmitted from bats to people.  It is possible that it passed from bats to people through an intermediate species, although this has not yet been proven.  What is clear, however, is that COVID-19 is a new virus (hence the references to it in early 2020 as “novel” coronavirus), so the adaptive immune system—B-cells and T-cells—has never encountered it and not yet had time to respond to it.  A person infected with COVID-19, therefore, is initially unable to fight the virus.  The virus will replicate inside their body before they develop antibodies, potentially spreading to another individual whose immune system is similarly unable to fight it.

As 2020 continued and more and more people became infected with COVID-19, the medical community’s understanding of this response became clearer.  Researchers found that 95% of people infected with COVID-19 will develop antibodies to combat the virus within eight days of first showing symptoms.  However, the magnitude of the response depends on the severity of the disease.  Those with milder disease demonstrate lower peak antibody levels than those with a more severe form.  Further research found that 90% of COVID-19-positive patients have detectable antibodies from 40 days up to 7 months post-infection.  

Vaccines Against COVID-19

The release of vaccines against COVID-19 marked a major milestone in the fight against the disease and was the result of a sophisticated understanding of how our immune system deals with the virus.  Two types of vaccine exist, and both work with the immune system to combat COVID-19, although in different ways.  The first delivers the genetic instructions from the virus to the body’s cells, which then produce the spike protein of the virus.  Without confronting the real virus, therefore, the adaptive immune system nonetheless responds by developing antibodies to the spike.  When it eventually is exposed to the real virus, the immune system can fight it.   The second type works like more typical vaccines, containing parts of the COVID-19 protein itself or using inactivated virus to stimulate the immune response.

What to Expect in 2021

Research into the immune response to COVID-19 will continue in earnest through 2021.  Although it is impossible to predict exactly what to expect, we are likely to see developments in three areas.  First, there will be a greater understanding of natural immunity, i.e., how the immune systems of those who have not been vaccinated respond to the virus.  Of interest will be how natural immunity is developed and, once present, how long it offers protection against the disease.   Second, as vaccines are more widely distributed, there will be more data on their effectiveness and side effects.  Finally, as the virus inevitably mutates, researchers will have to examine the ways in which these new variants compare to the original virus and whether existing vaccines will remain effective.


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