Long-term Immunity – Memory Cells Never Forget

To end the COVID-19 pandemic once and for all, we need long-lived protection.

Natural infection with SARS-CoV-2 induces humoral (antibodies) and cellular immune responses against the virus, but now we need to know for how long. 

We can see the light at the end of the tunnel, with life getting back to normal, but the pandemic is not over yet. We’re still worried about new waves with the latest variant in the autumn, and it’s relatively early in the COVID-19 pandemic to determine just how long protection against reinfection lasts. It’s taken time to figure out which types of immune cells are long-lived, how many there are, where they are in the body, what they’re reacting against, and now we need to know how long they’ll last. 

Recent research suggests that we should expect long-lived antibodies against SARS-CoV-2 because people who recuperated from SARS-CoV, a virus similar to SARS-CoV-2, had antibodies 17 years later. This is encouraging as long-lived immune responses are vital to getting the pandemic under control. In addition, more vaccinated and recovered people means fewer with severe or fatal versions of the disease.  

The immune system has a long memory, beginning during the initial viral infection when modifications to immune cells result in new cells that can live in the body for years or even decades. These memory cells react whenever they re-encounter the virus and protect us long-term. It’s like what happens with the measles: When we’ve had an infection once, we never get it again. 

Immunological memory is a complex defense mechanism, and for many viruses, there are several types of cells involved: The CD4 T helper lymphocyte coordinates the initial immune response and establishes immunological memory; the B lymphocytes that produce the antibodies that prevent viruses from entering our cells at all; the cytotoxic CD8 T lymphocytes that recognize and kill infected cells; and lastly, the memory plasma cells that continuously secrete antibodies long after the virus is gone.  

Lasting immunity to SARS-CoV-2

Infection with SARS-CoV-2 stimulates the body to make a broad immune response against several viral proteins, including the crucial spike protein, which is essential for the virus to enter cells and ultimately cause the COVID-19 illness. In contrast, vaccination only targets the spike protein and makes the immune memory response potentially less robust. A key to evaluating long-lasting immunity requires a complete understanding of memory responses following infection.  

Recently published scientific reports give us hope that long-term immunity to SARS-CoV-2 exists in many, if not most people. Researchers followed people for over a year after recuperating from COVID-19 and found that immune memory to SARS-CoV-2 lasted at least six months after infection in about 95% of subjects tested. They also found that the virus had triggered all the essential memory cells and antibodies. 

Other researchers identified memory plasma cells in the bone marrow that produce neutralizing antibodies to the SARS-CoV-2 spike protein. These antibodies are high during and after the initial infection and decline after a few months but seem to stabilize at a low protective level and might even be a predictor of long-term memory. 

In another recent study, researchers showed that antibodies stabilize 12 months after infection and that memory B cells can improve the quality of the antibody over time. More good news is that these antibodies can also neutralize some of the SARS-CoV-2 variant strains and that vaccines appear to boost the numbers of these persistent antibody-secreting plasma cells.

So, it looks increasingly like most of us will develop long-lasting protective immunity after a COVID-19 infection or after vaccination. But, of course, we need to keep following recovered and vaccinated people to figure out just how long immunity lasts and whether it protects against new variants. 

Still, a lot to feel good about!

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Dr. Michelle Epstein
Michelle Epstein is a medical doctor graduated from the University of Alberta in Canada, who has specialised in Internal Medicine at the University of British Columbia and Allergy and Clinical Immunology at Yale University. Since 2004, she has been a Lab Leader at the Medical University of Vienna’s Division of Immunology.

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