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COVID-19 Reinfection: Does Protective Immunity Develop After SARS-CoV-2 Infection?

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Since the beginning of the COVID-19 pandemic, several important questions have been answered but many still remain.


One key question, whether true reinfection occurs, has been clearly answered after the first patient was confirmed to be reinfected with a phylogenetically distinct SARS-CoV-2 strain by whole genome sequencing. Yet a follow-up question remains: What does that mean in terms of future immunity and vaccine efficacy?

"Reinfection with SARS-CoV-2 is confirmed for the first time with genetic evidence. Kwok-Yung Yuen and his colleagues at the University of Hong Kong identified a 33-year-old man who recovered from COVID-19 in April and tested positive again more than four months later, after returning from Spain via the United Kingdom. Genetic sequencing suggested that the second infection was caused by a virus that was genetically distinct from the one responsible for his initial bout."

Herd immunity and vaccine efficacy are two of the most debated topics in our fight against the pandemic, and they are both strongly interconnected with how people’s immune systems respond to the novel coronavirus.

What Can We Learn from Available Evidence?

Cases with suspected or possible reinfection have now been reported in different parts of the world. This evidence sheds light into what type of immunity to the virus can be expected to develop, either triggered by previous infection or a vaccine.

Earlier in the pandemic researchers were eager to find out whether true reinfection occurred. Later it was learned that testing positive after recovery does not necessarily indicate reinfection. Some studies have reported positive reverse transcription polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 in patients with laboratory-confirmed COVID-19 following clinical improvement and negative results on two consecutive tests. However, patients did not develop new or worsening symptoms, and these positive tests usually occurred shortly after the negative tests, raising the possibility of persistent virus shedding versus reinfection.

At the time of this writing, at least six cases of reinfection have been reported and at least one was confirmed by whole genome sequencing to be a phylogenetically distinct SARS-CoV-2 strain. The patient was asymptomatic at the second infection, and further serological analysis confirmed immune system response by the production of fresh neutralizing antibodies.

Understanding the characteristics and frequency of reinfection is essential as it could improve the knowledge of acquired immunity after natural infection. The protective role of antibodies or T-cell-induced immunity against SARS-CoV-2 is still not elucidated. It appears that the magnitude of the antibody response is associated with disease severity, indicating that antibody-related immunity against the virus may not be long-lasting in persons who experienced asymptomatic infection or mild illness.

This evidence suggests that the first SARS-CoV-2 infection triggers an immune response in most people, but the immunity may diminish over time. This appears to be more likely in patients with a mild primary infection, which was the case for the six recorded reinfections. The patients were relatively young, had mild primary infection, and reinfections presented as mild disease or asymptomatic infection.

While it is not known how strong and long-lasting the immune response will be to this virus, preliminary evidence suggests that people who developed immunity are better equipped to cope with the virus. In these reported cases of SARS-CoV-2 reinfections, the immune system was primed to recognize and fight the virus, and infections have been cut short. This type of immune response is called “functional immunity,” and even if it can disappear over time, i.e., waning immunity, reinfections will still generally be less severe than the initial episode.

This natural immune response has been documented with the four coronaviruses that cause about 15% of common colds: Reinfections can occur with these seasonal coronaviruses after a relatively short period of time, e.g., 90 days. The immunity generated to SARS-CoV (the virus identified in 2002) appears to last two to three years. SARS-CoV-2 is closely related to SARS-CoV, and both viruses share the same host receptor, the angiotension-converting enzyme. Thus, the duration of SARS-CoV-2 immunity might vary between several months and a couple of years depending on an individual’s immune status and the degree of immunity generated by the first infection.

While reinfections appear to be uncommon now, it is possible that the reported SARS-CoV-2 reinfections represent an underestimate due to insufficient testing, especially early in the pandemic, and clinically asymptomatic infections. The type of immunity humans will develop to the virus remains unknown; thus far experts believe that most will fit into either the functional or waning immunity categories.

This evidence also raises the possibility that a vaccine may not provide sterilizing immunity, defined as immune status after vaccination that prevents virus infection of the host. Vaccinated individuals may still get the mild form of the disease and may be able to transmit the virus, hence public health measures still need to be followed. Thus, it is possible that vaccination will have a substantially greater impact on preventing severe disease than on preventing milder symptoms or acquisition of infection. Notably, however, an experimental coronavirus vaccine seems to have completely prevented infection in most primates.

See also: The Old, the New, and the Borrowed: SARS-CoV-2 Vaccines and Beyond

Summary

There is limited human experience with the novel coronavirus, but evidence suggests that over time our immune system will learn how to cope with the virus to some degree. Insurers need to be aware that confirmed SARS-COV-2 reinfections increase the likelihood that underwriters will encounter this medical history on insurance applications. However, at this time, the possibility of reinfection does not suggest additional mortality and morbidity implications, but it does imply that individuals who have been infected once cannot be definitively considered to be immune. Although confirmed reinfections appear to be uncommon events, more evidence and longer follow-up time is required to better understand duration of immunity, transmissibility, and the likelihood and implications of reinfection.


References

  1. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1275/5897019
  2. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-epidemiology-virology-and-prevention?sectionName=Immunity%20and%20risk%20of%20reinfection&search=covid%2019%20reinfection&topicRef=127454&anchor=H1575856513&source=see_link#H1575856513
  3. https://www.nature.com/articles/d41586-020-00502-w
  4. https://jamanetwork.com/journals/jama/fullarticle/2759815
  5. https://www.statnews.com/2020/08/25/four-scenarios-on-how-we-might-develop-immunity-to-covid-19/ 
  6. https://science.sciencemag.org/content/368/6494/948?_ga=2.86881368.1154229161.1590933462-3816932.1589550741
  7. https://www.ecdc.europa.eu/sites/default/files/documents/Re-infection-and-viral-shedding-threat-assessment-brief.pdf
  8. https://www.nature.com/articles/s41586-020-2456-9
  9. https://www.cmaj.ca/content/192/34/E982

The Author

  • Dr. Georgiana Willwerth-Pascutiu
    Vice President and Medical Director 
    Global Medical
    RGA International Corporation

Summary

What does SARS-CoV-2 reinfection mean in terms of future immunity and vaccine efficacy? RGA's Dr. Georgiana Willwerth-Pascutiu reviews available evidence and warns insurers that confirmed reinfections increase the likelihood that underwriters will encounter this medical history on insurance applications.
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  • coronavirus
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  • Dr. Georgiana Willwerth-Pascutiu
  • genetic evidence
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  • serological analysis
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