Why do some people have natural resistance to coronavirus?

The novel coronavirus, SARS-CoV-2, is the focus of acquired immunity research, an important step in vaccine development.

Understanding T-cell centered acquired immunity has guided vaccine development and also helped explain why some people mount a stronger immune response to this virus as well.

We have summarized these findings, including existing studies and updated research in light of new variants, on T-cell responses for you.

We present 3 noteworthy studies on this topic:

What are T cells? Why are they important in COVID-19?

T cells are among the cells of our acquired immune system. They are divided into two types: cytotoxic T cells (CD8+) and helper T cells (CD4+). They perform their functions by recognizing antigens presented through MHC proteins.

In one study, antigens specific to SARS-CoV-2 were used to obtain virus-specific T cells from a person who had recovered from COVID-19. CD4+ T cells respond to the virus’s spike protein, the main protein targeted by vaccines. CD4+ T cells also respond to proteins such as nsp3, nsp4, ORF3a and ORF8, while CD8+ T cells target the viral spike and M proteins.

Another important finding concerned people whose prior exposure to SARS-CoV-2 was absent. Immune tests showed that these individuals had CD4+ T-cell responses to spike proteins ranging from 40% to 60%. Researchers think this may be due to the similarity of SARS-CoV-2 to other coronaviruses that cause the common cold.

Another study conducted in Ecuador

Another study from Ecuador highlights preexisting immunity to SARS-CoV-2 and differences in immune responses at individual and community levels. Using the rapid, inexpensive interferon-gamma release assay (IGRA), the study measured T-cell immune responses in people who had recovered from the disease and those who had never been exposed. Before discussing the results, let’s explain what an interferon-gamma release assay is.

An interferon-gamma release assay (IGRA) is based on T lymphocytes releasing a cytokine called interferon gamma (IFN-γ) when exposed to specific antigens. Used more often to diagnose tuberculosis, this test is also used for SARS-CoV-2. To prevent existing IFN-γ levels in recently recovered individuals from misleading the research, the experiment was performed about 3 months after their recovery.

A blood sample was taken from each participant. Stimulants such as the SARS-CoV-2 spike protein were added to the samples, followed by a 24-hour wait. IFN-γ production was then assessed. It was 80% in patients who had previously recovered from COVID-19, compared with 44% in people who had not previously been exposed to the disease.

A limitation should be noted here: because the study involved a small group, we cannot say it represents the general population.

In conclusion, these two studies show that nearly half of people in the community have at least partial acquired immunity to SARS-CoV-2, probably thanks to previous infections with different coronaviruses.

Why is SARS-CoV-2 infection milder in children?

According to findings reported from Australia, the main reason is that children have a stronger innate immune response to SARS-CoV-2 (type 1 IFN and type 3 IFN) than adults. 

In this study, ACE-2 and TMPRSS-2 protein expression was similar in adult and child nasal epithelial cells. 

According to this study published in bioRvix, ACE-2 and TMPRSS-2 expression was similar in nasal epithelial cells from children and adults. However, children showed a stronger interferon-mediated innate immune response and lower infectious viral replication in nasal epithelial cells.

What effect do variants have on immunity?

To understand this better, we first need to understand how a virus invades a cell.

Viruses attach to and enter the cells they infect using proteins called spike proteins on their surface. SARS-CoV-2 enters cells through its spike protein interacting with ACE2 receptors in our bodies, with help from TMPRSS2. One reason it has such destructive effects on our lungs is the abundance of ACE2 receptors in the tissue there.

Mutations cause viral variants to emerge (see What is the new coronavirus variant-mutation?). Mutations can occur in any viral protein, including the spike protein the virus uses to bind to cells or any of its other proteins.

We mentioned that T cells provide immunity mainly through these spike proteins. The mRNA vaccines from companies such as Moderna and Pfizer/BioNTech also target the viral spike protein. We can therefore say that a mutation in a protein other than spike will not affect immunity. But what if the spike protein mutates?

Then we face 2 situations:

1. In this scenario, the spike mutation disrupts the virus’s interaction with the receptor to which it binds. In such a situation, there is no need to worry: the virus has inactivated itself.
2. In this scenario, the mutation both preserves the virus’s interaction with the receptor and allows it to evade the immune system. These are dangerous mutations.

Which of these categories do current variants fall into? A recent study examined T-cell responses to the B.1.1.7, B1.351, P.1 and CAL.20C variants. According to the preprint findings, T-cell responses in people who had recovered from SARS-CoV-2 and in vaccinated people were unaffected by the mutations present in these variants.

However, an article published in Nature on March 9 described another concerning SARS-CoV-2 variant from South Africa. Carrying three critical mutations in its receptor-binding region (K417N, E484K, N501Y), this new variant is thought likely to be more transmissible and more successful at escaping immune responses, such as neutralizing antibodies.

RELATED TOPICS

• COVID-19: current statistics for the world and Turkey
• Breaking news and scientific developments about coronavirus

Manage preferences to view external content

Manage preferences to view external content