An arms race between SARS-CoV-2 and our immune systems


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An arms race between SARS-CoV-2 and our immune systems

Coronaviruses are a family of viruses that have been causing mild to severe respiratory and intestinal diseases in both humans and animals for decades. Most human coronaviruses cause the common cold; however, some types such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) have caused outbreaks and epidemics in 2002/2003 and 2012, respectively. The most recent coronavirus which has created global havoc and affected everyone’s lives in one way or another since its initial identification in 2019 is SARS-CoV-2. Similar to its predecessors SARS and MERS, SARS-CoV-2 is capable of causing severe disease with various long-term health impacts which are not fully understood. 

Figure 1: Structure of a coronavirus. Adapted from “Human Coronavirus Structure”, by (2021). Retrieved from

The emergence of a new coronavirus and our inability to control its rapid spread weren’t our only concern, every couple of weeks or months we hear about new variants with different disease and transmissibility profiles from the original SARS-CoV-2. This raises the question, how protected are we against these new variants? 

What are COVID-19 variants and how do they emerge?

During viral replication, the viral genome can acquire random genetic mutations (which are errors in copying of the genome). This process occurs constantly and is quite advantageous for the virus as the mutations allow it to adapt to its surroundings, move from one host species to another,  and evade the antiviral mechanisms exerted by our immune system. These mutations could allow the virus to become more transmissible or capable of causing severe versions of the disease. 

Particularly, mutations on the spike protein of SARS-CoV-2 (Figure 1) are of importance. This is the region of the virus that recognizes and binds to host cell receptors, and therefore initiates the infection. Additionally, because the spike protein is the outermost part of the virus and also the viral region encoded by the covid vaccines, the immune systems of previously infected or vaccinated hosts can readily recognize the original spike protein. Consequently, mutations in the region could hinder the immune system’s ability to recognize the virus.

While this process continuously produces new variants, most of these are not a significant cause of concern and do not persist for long in the population. But some variants, such as Delta and Omicron, may have an increased transmission rate, cause more severe disease, or may impact the effectiveness of treatments and vaccines. These are classified as Variants of Concern (VoC).

Does exposure to early COVID-19 variants provide protection against new variants, like Omicron? 

    Gao et al. (2022) sought to answer this question in relation to the omicron variant which has increased transmissibility owing to spike protein mutations allowing a higher receptor-binding affinity for its host receptor. Many reports and recent data indicate that the neutralizing antibodies produced against the original SARS-CoV-2 (Figure 2b), through infection or vaccination, are much less effective against Omicron variant, possibly due to a decreased ability to recognize it. Despite this, most people did not develop a severe disease which suggests other areas of the immune system still recognize and provide some protection against the virus. 

Figure 2: Mechanisms of T and B cells against viruses. Adapted from “Recruitment of T and B cells by Antigen Presenting Cells”, by (2021). Retrieved from

Besides the neutralising antibodies, previous evidence also suggests that SARS-CoV-2 infections or vaccination also produce strong T cell responses which can also hinder virus replication and disease severity (Figure 2a). Therefore, it is possible that T cell responses generated against the original virus are still effective against Omicron and development of severe disease. 

While neutralising antibodies bind to virus particles and then prevent the virus from infecting our cells, the T cell response targets cells that are already infected by the virus and kills the infected cells (Figure 2a). Once the virus infects a host cell, the infected cell processes small portions of the virus (such as the spike protein) and displays them on its surface using major histocompatibility complex (MHC) molecules. By displaying a portion of the virus on their surface, these infected cells notify the surrounding immune cells, such as T cells, that they have been infected. T cells specific for that portion of the virus are then able to recognize the MHC-antigen complex, and then initiate their “killing” response.

The recent study by Gao et al. (2022) sought to answer this question by comparing spike protein specific activation of the peripheral blood mononuclear cells – some of your white blood cells – in three groups: 1) doubly vaccinated individuals with Pfizer, 2) convalescent individuals that had a mild or severe infection and 3) unvaccinated and uninfected individuals. Through their experiments, they observed that the spike protein-specific T cell response against omicron was significantly lower, although some response was there, in the convalescent individuals group relative to the response against the original spike protein. However, the vaccinated individuals group had a similar T cell response against both the omicron and original spike proteins. 

Overall, these results suggest the T cell responses produced against the original SARS-CoV-2 variant through either infection or vaccination can cross-recognize the omicron variant. However, prior infections provide relatively lower protection against omicron compared to people doubly vaccinated with Pfizer vaccines. While these results provide interesting insight into immune protection against new variants, it should be considered that they are obtained from comparing a small number of subjects possibly with other confounding variables that might have influenced the results. Additionally, the study only looked at the peripheral blood samples which provide valuable information, but are not a comprehensive representation of the full immune response exerted by our bodies.

Link to the original post: Gao, Y., Cai, C., Grifoni, A. et al. Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant. Nat Med (2022).

Additional sources

  1. Centers for Disease Control and Prevention. (n.d.). SARS-COV-2 variant classifications and definitions. Centers for Disease Control and Prevention. Retrieved February 7, 2022, from 
  2. Centers for Disease Control and Prevention. (n.d.). Omicron variant: What you need to know. Centers for Disease Control and Prevention. Retrieved February 7, 2022, from 
  3. Callaway, E. (2021). Beyond omicron: What’s next for Covid’s viral evolution. Nature, 600(7888), 204–207. 

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