Severity of COVID-19 Re-infections

When it comes to SARS-CoV-2, the severity of re-infections can range from milder to more severe. A systematic review conducted in 2020 revealed that approximately 68.8% of re-infection cases exhibited comparable severity to initial infections, while 18.8% were more severe, and only 12.5% were milder. However, the authors acknowledged that asymptomatic re-infections likely went unrecorded.

A more recent meta-analysis from 2021, which compiled data from 81 studies, indicated no significant differences in overall symptoms or severity between first-time infections and re-infections. Yet, when broken down further, individuals with re-infections showed higher occurrences of dyspnea, fatigue, and the need for oxygen support, suggesting a trend towards greater severity.

A notable study utilizing the extensive health care databases of the U.S. Department of Veterans Affairs examined a large cohort comprising 257,427 first-time infections, 38,926 re-infections, and a control group of 5,396,855 non-infected individuals. The findings indicated that six months post-re-infection, those with re-infections experienced significantly increased risks of all-cause mortality (24 excess cases per 1000), hospitalization (95 excess cases), and at least one chronic condition (200 excess cases) compared to those with their first infection, irrespective of vaccination status.

Critiques of this study include concerns about its methodology, particularly the age of participants and the high percentage of unvaccinated cases, which may skew results. Additionally, the timeframes for assessing risks after initial versus re-infection may not provide a full picture of re-infection outcomes.

Despite these critiques, the study's large sample size highlights a concerning trend: increasing long-term health complications with each re-infection.

Mild re-infections can still pose significant risks due to two main factors: the potential for long-COVID symptoms and the cumulative risk of severe disease with each successive infection.

The infecting variant significantly influences re-infection severity. According to the U.K.'s Office for National Statistics, re-infections with variants such as Alpha, Delta, and Omicron exhibited varying rates of symptomatic cases, with BA.4 and BA.5 indicating higher mortality in animal studies, suggesting an increase in virulence compared to earlier strains.

The Surge of Omicron Re-infections

Historically, COVID-19 re-infections were uncommon, with a 2021 review estimating a re-infection rate of roughly 1% over several months. However, this rate has surged to about 10% due to the emergence of the Omicron variant, recognized for its immune evasion capabilities. The U.K. reported a striking 20-fold increase in re-infection rates in January 2022 alone.

A surveillance study in South Africa observed that re-infection cases were rare during the Beta and Delta waves but spiked during the Omicron wave. Current data suggests that the more advanced BA.4 and BA.5 subvariants are even more contagious and immune-evasive than earlier strains.

While the original Wuhan-2019 variant had an R-naught (Ro) of 3.3, indicating one infected person could potentially infect three others, the BA.4 and BA.5 variants exhibit an estimated Ro of 18.6, substantially amplifying the threat of transmission.

Furthermore, recent research indicates that antibody responses from vaccinated or previously infected individuals are significantly less effective against the newer BA.4 and BA.5 subvariants.

Given the higher transmissibility and severity of these new variants, the expectation of increased COVID-19 infections and re-infections is not surprising.

Several nations, including France, New Zealand, and Australia, are witnessing a rise in COVID-19 cases once again.

While there is cause for concern, there is also room for cautious optimism. When BA.4 and BA.5 first appeared in South Africa, the resulting wave was significantly less severe than previous waves.

However, outcomes can vary widely from one country to another. Thus, even if BA.4 and BA.5 resulted in a less severe wave in South Africa, it cannot be assumed that other countries will experience the same. The possible clinical and long-term health implications of recurring Omicron infections are significant and should not be underestimated.

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