< Immunity

What is cross-protective immunity and can it protect me from COVID-19?

Text updated on 2020-06-16

Cross-protective immunity, in the case of COVID-19, is referring to the protection against SARS-CoV-2 infection due to the pre-existing adaptive immunity developed from the past exposure to another coronavirus. It is currently unknown whether this immunity can protect individuals from COVID-19 and whether it will reduce the intensity of the epidemic.

Cross-protective immunity is defined as protection against a given pathogen thanks to immunity acquired from past exposure to a related pathogen or its antigens. This protection reduces the severity of the disease caused by the pathogen, without necessarily preventing an infection.

The first report of cross-protective immunity dates back from the 18th century, when Jenner observed that individuals who previously suffered from cowpox were protected against smallpox and laid the foundation for vaccination. Besides vaccines, natural infections can also induce cross-protective immunity. For instance, during the H1N1 influenza pandemic in 2009, elderly people were less likely to develop the disease than children and young adults, probably because they had previously encountered similar H1N1 viruses that circulated several decades earlier.

In the case of COVID-19, cross-immunity to SARS-CoV-2 could be conferred by past exposure to other coronaviruses. The SARS-CoV-2 coronavirus is closely related to the SARS-CoV-1 virus responsible for the SARS epidemic in 2003, and to the HCoV-OC43 and HCoV-HKU1 viruses, two common causes of seasonal colds. It has been shown that the immune response triggered by HCoV-OC43 can recognize SARS-CoV-1. Similarly, blood samples collected prior to the COVID-19 outbreak are reactive against SARS-CoV-2. In addition, antibodies found in a patient infected with SARS-CoV-1 cross-react and neutralize SARS-CoV-2. Taken together, these observations indicate that some individuals infected with other coronaviruses have developed an immune response that recognizes and neutralizes the SARS-CoV-2 virus.

It is still unknown whether cross-immunity will be effective to protect from COVID-19, and if so, for how long. If cross-immunity occurs for a substantial fraction of the population, it could influence long term dynamics of COVID-19 outbreaks. However, protection related to cross-immunity may vary in different populations, for instance, based on their demography, geographical habitat, previous exposure to coronaviruses and level of SARS-CoV-2 exposure. In the last few months, we observed that some communities are poorly protected as an extremely high percentage (>80%) of people in specific clusters have been infected by SARS-CoV-2, suggesting little cross-immunity. Further research is necessary to better understand the influence of cross-protective immunity on the dynamics of COVID-19 epidemics.

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Original comments by Edward Jenner on smallpox protection conferred by a previous cowpox infection.

Jenner, E. (1798). "An Inquiry into the Causes and Effects of the Smallpox Vaccine, or Cow-Pox, 1798". On Vaccination Against Smallpox (Lit2Go Edition).

Analysis of pre-existing immunity to the H1N1 flu virus in 2009.

Hancock, K., Veguilla, V., Lu, X., Zhong, W., Butler, E. N., Sun, H., ... & Brammer, T. L. (2009). Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. New England Journal of Medicine, 361(20), 1945-1952.

Analysis of the antigenic determinants from the 2009 swine-origin H1N1 pandemic virus and from previous seasonal H1N1 viruses.

Greenbaum, J. A., Kotturi, M. F., Kim, Y., Oseroff, C., Vaughan, K., Salimi, N., ... & Peters, B. (2009). Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population. Proceedings of the National Academy of Sciences, 106(48), 20365-20370.

Analysis of the immune response against SARS-CoV-2 in 10 non-hospitalized patients recovered from illness COVID-19 and 11 healthy, unexposed individuals. Immune cells recognizing SARS-CoV-2 were detected in all COVID-19 patients as well as in four healthy, unexposed individuals.

Grifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., ... & Marrama, D. (2020). Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell.

Analysis of the reactivity against SARS-CoV-1 of serum collected from 8 patients infected with HCoV-OC43.

Patrick, D. M., Petric, M., Skowronski, D. M., Guasparini, R., Booth, T. F., Krajden, M., ... & MacDonald, D. (2006). An outbreak of human coronavirus OC43 infection and serological cross-reactivity with SARS coronavirus. Canadian Journal of Infectious Diseases and Medical Microbiology, 17(6), 330-336.

Identification of antibodies recognizing and neutralizing the SARS-CoV-2 coronavirus in a patient previously infected with the SARS-CoV-1 virus

Pinto, D., Park, Y. J., Beltramello, M., Walls, A. C., Tortorici, M. A., Bianchi, S., ... & Peter, A. (2020). Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature, 1-10.

Modeling of the COVID-19 epidemic taking into account a possible cross-protective immunity conferred by common cold coronaviruses.

Kissler, S. M., Tedijanto, C., Goldstein, E., Grad, Y. H., & Lipsitch, M. (2020). Projecting the transmission dynamics of SARS-CoV-2 through the post pandemic period. Science, 368(6493), 860-868.

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