COVID-19 Reinfection Risk

October 18, 2021

Already a catastrophe affecting billions of lives across the planet, the COVID-19 pandemic could become further prolonged depending on the risk of reinfection. To investigate the reinfection rate, researchers have reviewed the charts of previously infected patients [1]. However, much remains uncertain due, at least in part, to patients’ varying immune reactions to the disease [1]. For instance, while some people exhibit sufficient immune responses to SARS-CoV-2 more than six months following their initial infection, a significant minority of patients exhibit seroreversion [1]. As a result, testing the frequency of seroreversion, consulting large datasets, and considering how at-risk groups will be affected are necessary to gauge the extent of this problem.

Haverall et al. tested reinfection rates using data provided by 1,884 healthcare workers (HCWs) and 51 hospitalized patients who had previously contracted COVID-19 [2]. The subjects were seen eight months after previous infections [2]. Some had been asymptomatic, while others had experienced severe bouts of the illness [2]. Data showed a protective effect of 95.2% from seroconversion (comparing HCWs who continued to be positive for anti-spike IgG at follow-up with HCWs who were negative) [2]. The researchers were also able to detect SARS-CoV-2-specific T-cell responses in the majority of subjects [2]. Overall, most seropositive participants remained seropositive for up to 8 months, regardless of initial disease severity, and the presence of antibodies was associated with significantly reduced risk of reinfection.

In September 2020, a larger dataset, collected in Qatar using 133,266 laboratory-confirmed SARS-CoV-2 cases, reported a low reinfection rate of 0.2% [1]. However, a more recent and sizable study has emerged, contesting this minimal reinfection rate. Hansel et al.’s analysis made use of Denmark’s policy of regularly testing all individuals, regardless of symptoms, to determine the risk of reinfection [3]. By contrast, the dataset from Qatar only consisted of people who were symptomatic and thus compelled by their government to take a SARS-CoV-2 test, suggesting that a significant population was left out of the dataset, potentially including people who were reinfected but were asymptomatic [1]. Accordingly, the researchers analyzed data from 10.6 million tests taken by 4 million people [3]. Ultimately, they found that the previously infected had only an 80.5% protection rate against reinfection [3]. Shockingly, this rate decreased to 47.1% among the population aged 65 and older [3]. Given that the Hansel et al. study is the largest of its type, it may be closest to representing the true reinfection rate [1].

One reason for these high rates of reinfection could be the significant chance of seroreversion among previously infected individuals. Peghin et al. checked in with 546 previously infected individuals 10 months after infection [4]. They found that, of the 5.7% of patients who had been reinfected, 1.5% were seroreverted, and 3.6% were seronegative [4]. Fortunately, Peghin and her colleagues also noted that all of the reinfections were asymptomatic or, at worst, mild [4].

Nevertheless, reinfection may disproportionately affect at-risk groups, so precautions must be taken wherever possible to avoid it. Risk factors for SARS-CoV-2 reinfection include older age and preexisting diseases, such as obesity, cancer, and diabetes [5]. Patients with primary or secondary antibody deficiency syndrome may also exhibit weakened immune responses to reinfection, although research indicates that, like the general population, they are significantly less likely to be reinfected than infected in the first place [6].

To minimize the adverse effects of SARS-CoV-2 reinfection, vaccination can be very helpful [7]. A study of Kentucky residents found that unvaccinated people were reinfected at a rate 2.34 times higher than their vaccinated counterparts [7]. As recommended by the CDC, all eligible people, regardless of their infection history, should receive the COVID-19 vaccination to minimize risk [7].

References

[1] R. J. Boyton and D. M. Altmann, “Risk of SARS-CoV-2 reinfection after natural infection”, The Lancet, vol. 397, no. 10280, p. 1161-1163, March 2021. [Online]. Available: https://doi.org/10.1016/S0140-6736(21)00662-0.

[2] S. Haverall et al., “Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19,” Journal of Internal Medicine, p. 1-9, August 2021. [Online]. Available: https://doi.org/10.1111/joim.13387.

[3] C. H. Hansen, “Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study,”The Lancet, vol. 397, no. 10280, p. 1204-1212, March-April 2021. [Online]. Available: https://doi.org/10.1016/S0140-6736(21)00575-4.

[4] M. Peghin et al., “Low risk of reinfections and relation with serological response after recovery from the first wave of COVID-19,” European Journal of Clinical Microbiology & Infectious Diseases, p. 1-8, August 2021. [Online]. Available: https://doi.org/10.15585/mmwr.mm7032e1.

[5] S. Ahmad et al., “Reinfection risk of novel coronavirus (COVID-19): A systematic ‎review of current evidence,” World Journal of Virology, vol. 9, no. 5, p. 79-90, December 2020. [Online]. Available: https://doi.org/10.5501/wjv.v9.i5.79.

[6] A. S. Breathnach et al., “Prior COVID-19 protects against reinfection, even in the absence of detectable antibodies,”Journal of Infection, vol. 83, no. 2, p. 237-279, August 2021. [Online]. Available: https://doi.org/10.1016/j.jinf.2021.05.024.

[7] A. M. Cavanaugh et al., “Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination — Kentucky, May–June 2021,” Morbidity and Mortality Weekly Report, vol. 70, no. 32, p. 1081-1083, August 2021. [Online]. Available: https://doi.org/10.15585/mmwr.mm7032e1.