Antibodies to the virus that causes COVID-19 are keys to immunity. [Credit: Compilation by Nancy R. Gough, BioSerendipity, LLC using Icons made by Freepik from Flaticon]

Immunity and a Mutating Virus: Challenges along the Path for COVID-19

If long-term immunity is not achievable, SARS-CoV-2 could become one of the viruses that affect the population year after year.

SARS-CoV-2 is an RNA virus of the coronavirus family. Of the 36 RNA virus families that cause human diseases, we only have vaccines for 10. In some cases, this is because the viruses in the family do not cause severe disease. So, there is no reason to pursue development of a vaccine. In others, it is because effective, safe vaccines have been difficult to create. Some vaccines, like the polio vaccines, provide durable immunity; others, like influenza vaccines, must be updated to provide immunity to new strains of the virus. It seems possible that there will not be a safe, effective vaccine against SARS-CoV-2 in the near future.

Immunity to a Mutating Virus

Genetic replication is an error-prone process that results in mutations. How quickly a virus mutates depends on how it replicates and whether it has an ability to repair errors that are introduced. RNA viruses mutant faster than DNA viruses. Coronaviruses tend to mutate more slowly than other RNA viruses because their enzymes involved in replicating their genetic material has some ability to “proofread.”

If the virus does not mutate into a less virulent (disease-causing) form, then eventually most people would get exposed to the virus. Just like now during the pandemic, some would get very sick, some would die, and some would have mild illness. Even Dr. Michael Ryan of the World Health Organization (WHO) is beginning to think that this SARS-CoV-2 may become an endemic virus, like some influenza viruses. This means that the virus will circulate among the global population, causing some rate of annual infection. Or as Dr. Ryan said in a press briefing on 13 May 2020, “This virus may never go away.”

If the immune response to the virus produces an effective adaptive response and the virus does not mutate to evade this response, some people will naturally develop some amount of immunity to SARS-CoV-2 after exposure to the virus. Thus, those who recover from COVID-19 would likely have some level of immunity to the virus that will either prevent them from getting COVID-19 again or prevent them from getting serious symptoms of the disease at least for a period of time.

We do not know if people will develop immunity, how many people will develop immunity, or how long that immunity will last. We do know that SARS-CoV-2 is mutating, as all viruses do. Many of the changes in the RNA of the virus do not change the proteins in the virus. Some do change the proteins but have no effect on the function of the protein or the ability of the immune system to recognize the viral proteins. Some change the function of the protein or the ability of the immune system to recognize the protein.

It seems likely that, even if some develop immunity, some will lose their immunity over time as the virus changes and mutations let the virus escape immune recognition. Mutation of the viral proteins needed for a virus-neutralizing immune response is one reason that developing a vaccine is challenging.

Tracking the amino acid mutations in SARS-CoV-2. The x axis is number of mutations. The colors represent countries with the patient with the virus. Each circle represents the sequence of the virus from a specific patient. At the time of this analysis, 2 of the viruses had more than 20 mutations compared to the first one sequenced. [From https://nextstrain.org/ncov/global?branchLabel=aa&m=div&p=full&r=division].

In addition to influencing immunity, mutations could changes properties of the virus related to virulence, which is the ability to spread and cause disease. The virus could become more virulent or less. Indeed, a preprint in medRxiv reported differences in virulence using a test that involved infecting cultured cells with virus isolated from patients with viruses with different mutations. Some of the mutated viruses were less virulent, some were more virulent, and some had an intermediate virulence.

A Slow Path to Natural Immunity

To achieve any immunity in the absence of a vaccine, people need to become infected with SARS-CoV-2. By limiting the spread of the pandemic, the world has reduced deaths due to COVID-19 and given the healthcare systems time to increase capacity for patients. However, limiting the spread also reduced the how fast the population will naturally develop immunity to the virus, if this is possible.

Population immunity is sometimes referred to as “herd immunity.” Herd immunity refers to the percentage of the population that must become immune to a pathogen so that the pathogen does not cause epidemic spread of infection. This percentage varies based on the average number of people a single infected individual infects. The reasons that the road maps to the new normal involve a vaccine is that vaccination is a way to medically induce herd immunity. For SARS-CoV-2, scientists predict that herd immunity will require ~50–70% of the population to have immunity.

Studies of the antibody and T cell responses to SARS-CoV-2 will help determine if herd immunity is possible. Such information will also inform vaccine development.

Related Reading

E. C. Smith, N. R. Sexton, M. R. Denison. Thinking Outside the Triangle: Replication Fidelity of the Largest RNA Viruses. Annu. Rev. Virol. 1, 111‐132 (2014). DOI: 10.1146/annurev-virology-031413–085507

H. Yao et al., Patient-derived mutations impact pathogenicity of SARS-CoV-2. medRxiv 2020.04.14.20060160 (23 April 2020). DOI: 10.1101/2020.04.14.20060160

G. A. D’Souza and D. Dowdy, What is Herd Immunity and How Can We Achieve It With COVID-19? Johns Hopkins Bloomberg School of Public Health (10 April 2020) https://www.jhsph.edu/covid-19/articles/achieving-herd-immunity-with-covid19.html

L. Cook and E. Becatoros, As new clusters emerge, WHO warns virus may be here to stay. MedicalXpress (13 May 2020) https://medicalxpress.com/news/2020-05-clusters-emerge-virus.html

Viruses and Vaccines: A Basic Flowchart of Viral Families. American Scientist 106, 76 (2018). DOI: 10.1511/2018.106.2.76 https://www.americanscientist.org/article/viruses-and-vaccines-a-basic-flowchart-of-viral-families

Genomic epidemiology of novel coronavirus- Global subsample. Nextstrain (accessed 16 April 2020) https://nextstrain.org/ncov/global

Also of Interest

N. R. Gough, Variants, Lineages, and Strains of Coronavirus. https://medium.com/@ngough_bioserendipity/variants-lineages-and-strains-of-coronavirus-7a71a0e699d7 (25 May 2020)

Ph.D. scientist with a passion for scientific communication and > 20 years editorial experience

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