Can coronaviruses elicit long-lasting immunity?

There is more to immunity than antibodies. This article will feature several studies that show that immunity against SARS-CoV-2, the virus that causes COVID-19, can exist in those who had COVID-19 before, those who have not had COVID-19, and those who are not vaccinated. Each study shows a different way the different cells that provide immunity.

The first two studies show the presence of immunity among those who had COVID-19.

Bone Marrow Plasma Cells

Nature published a study, SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans, that involved 188 COVID-19 cases that were followed for 18 months. Their result showed that while the antibody levels decrease after 7 months, the memory B cells in the bone marrow produce antibodies specific to SARS CoV-2 are still around.

Those bone marrow plasma cells can crank up the production of antibodies when they reencounter SARS-CoV-2.

Memory B cells, CD8+ T cells, and CD4+ T cells

A study from Science, Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection, showed IgA, Memory B cells, CD8+ T cells, and CD4+ T cells specific for SARS-CoV-2 are present months after providing durable immunity.

Immunoglobulin A against the spike protein or Spike IgA was present 6 to 8 months after infection. IgAs are a type of antibody located on the inner linings of the respiratory tract and gastrointestinal tract. IgAs are the first line of defense and prevent germs from entering the cells. No viral entry to cells → , no replication → , no infection.

IgAs stop the infection before it happens. COVID-19 vaccines only induce IgG production and not IgA.

Plasma Memory B cells float around in the blood in a quiescent stage. They remember the original antigen that activated their parent B cells. Once they reencounter the antigen, they start producing antibodies.

On subsequent exposures, the specific antibodies will be made in greater amounts at a fraction of the time compared to the first infection. Clinically, this translates to fewer symptoms and faster recovery from the disease.

CD4+ cells send signals to the macrophages and other immune system cells to kill the target cells. They’re like generals. They coordinate the different parts of the immune system to execute an efficient and orderly immune response.

CD8+ T cells are also called cytotoxic T lymphocytes. They have three functions once they recognize an infected cell.

First, they secrete cytokines like tumor necrosis factor-alpha or TNF-α and interferon-gamma or INF-γ that have antiviral effects. Second, they poke holes in the infected cells allowing granzymes to enter and destroy the viruses inside. After that, the CD8+ T cells move on to kill more infected cells. A process called serial killing.

Third, CD8+ cells activate the caspase cascade. The caspase cascade calls in cytokines or signaling molecules that eventually lead to the orderly death or apoptosis of the infected cells. Doing so, they clean up the “battlefield” to restore normalcy in the tissues.

The caspase cascade also induces fratricide or killing of other CD8+ T cells at the end of the immune response. Fratricide is one way of removing the excess CD8+ cells to avoid destroying normal cells or an autoimmune response.

The next two studies are about people who have not been infected with COVID-19 but still have immunity. They have been presented before on this website but will be summarized here.

The two studies below show how immunity to COVID-19 can be present in those who have not had COVID-19.

CD4+ Cross-Reactivity between Seasonal Coronavirus Colds and COVID-19 is an article that showed the presence of CD4+ cells against SARS-CoV-2 in people who never had COVID-19.

The CD4+ reactive T-cells present in the healthy, non-COVID-19 patients most likely came from previous infections with seasonal coronaviruses. These coronaviruses are the 229E, NL63, OC43, and HKU1.

These seasonal coronaviruses are responsible for 20-30% of common colds yearly.

The time-course of an immune response begins with the initial pathogen encounter (or initial vaccination) and leads to the formation and maintenance of active immunological memory. Image: Wikipedia

Another article, 60% may already have Immunity to COVID-19, included four studies that showed that CD4+ T-cells are present because in people uninfected with COVID-19.

The reason that immunity is possible in the uninfected is that the spike protein of coronaviruses are genetically conserved. This means most of the gene sequence of the spike protein is the same in all coronavirus species, whether it be the common coronaviruses, SARS, MERS, or SARS-CoV-2.

What is different about the SARS-CoV-2 spike protein sequence is the insertion of the bat coronavirus sequence in its spike protein, among others. But that is another topic for another article.

How long can the immunity last?

A study from Nature, SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls showed that people infected with SARS and those who never had SARS have reactive T-cells against the nucleocapsid-protein or N protein of the SARS-CoV-2 17 years after the SARS infection. Here is a quote from the abstract.

Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections. Little is known about the presence in humans of pre-existing memory T cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36).

In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2.

We also detected SARS-CoV-2-specific T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specific T cells in uninfected donors exhibited a different pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein.

Epitope characterization of NSP7-specific T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to ‘common cold’ human-associated coronaviruses.

Thus, infection with betacoronaviruses induces multi-specific and long-lasting T cell immunity against the structural N protein.

Their conclusion is limited to 17 years because that is the time difference from the SARS infection to the time of the study. The immunity may last longer.

Conclusion

There is more to immunity than antibodies. That is why someone can have immunity to the SARS-CoV-2 without getting vaccinated.

Knowledge about Covid-19 is rapidly evolving. Information may update as new studies are made. Stay current by subscribing. Feel free to share.

Don’t Get Sick!

Interesting readings:

References:

Dan et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. SCIENCE05 FEB 2021

Turner, J.S., Kim, W., Kalaidina, E. et al. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Nature (2021). https://doi.org/10.1038/s41586-021-03647-4

Image Credit: By Webridge – File: Immune response.jpg, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=37968012

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