Reinfections lower long COVID risk but raise cumulative burden

By Dr. Chinta SidharthanReviewed by Susha Cheriyedath, M.Sc.May 14 2025

New data from Canadian healthcare workers show that while reinfections are less likely to cause long COVID, the risk stacks up, especially for those hit hard the first time or infected early in the pandemic.

Study: Long COVID risk and severity after COVID-19 infections and reinfections in Quebec healthcare workers. Image Credit: Niphon Subsri / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Can a second bout of coronavirus disease 2019 (COVID-19) be just as harmful in the long run as the first? In a study posted to the medRxiv preprint* server, Canadian researchers found that healthcare workers in Quebec had a significantly lower risk of developing long coronavirus disease (long COVID) after reinfections than after a first infection. However, the cumulative risk of long COVID increases with each additional infection, so the overall burden remains high.

Long COVID

Long COVID, also known as post-COVID-19 condition, is a condition marked by symptoms that persist for at least 12 weeks following a COVID-19 infection. These symptoms range from fatigue and breathlessness to memory issues and can severely affect daily life.

Globally, over 400 million people may be living with lingering effects of the virus. Despite the growing recognition of long COVID, many questions remain about who is most at risk and how this risk evolves with repeated infections.

A major challenge is that many symptoms overlap with other common conditions, making it difficult to pinpoint COVID-19 as the cause. In addition, the absence of specific diagnostic biomarkers means that long COVID is usually identified based on symptom duration and attribution by the patient. However, as newer variants of the virus continue to spread, people are more likely to experience reinfections. Therefore, understanding long COVID’s true burden, especially after repeat infections, is critical.

The current study

This population-based study used a retrospective cohort design to investigate long COVID risk and severity among healthcare workers in Quebec, Canada. The research team conducted an electronic survey between May 16 and June 15, 2023, targeting workers, such as doctors, nurses, and respiratory therapists, who were active in the provincial healthcare system during the pandemic.

The survey collected data on demographics, employment, infection history (including lab-confirmed infections), symptom presence and duration, severity of each COVID-19 episode, and vaccination status. The researchers also assessed ongoing symptoms and cognitive difficulties and their impact on functional status.

Long COVID was defined as symptoms attributed to COVID-19 lasting at least 12 weeks (three months), and the cases were classified as prevalent, resolved, or undetermined. Additionally, severity was graded based on whether symptoms were mild, moderate, or severe. Control groups consisting of participants who never had COVID-19 and those who had recovered within 12 weeks were also included.

To assess possible participation bias, a parallel telephone survey was conducted among 7,500 randomly selected non-respondents to the online survey and 3,000 non-vaccinated healthcare workers without email access, for a total of 10,500 participants invited to the telephone survey. This shorter survey included five questions about COVID-19 history and persistent symptoms.

Furthermore, variant information for each infection was inferred based on the timing of infection and dominant circulating strains in Quebec. The risk of long COVID was calculated based on infections occurring at least 12 weeks before survey completion, and comparisons were made between first infections and reinfections.

Key findings

The study found that long COVID remains a widespread and disabling condition among healthcare workers, with about 17% of those who had COVID-19 reporting symptoms lasting at least 12 weeks. However, the risk of developing long COVID was approximately three times higher after a first infection compared to reinfections.

While the risk increased with each additional infection, up to 37% of those with three infections experienced long COVID, the likelihood of developing long COVID was significantly lower for each reinfection than for the initial episode. The highest risk was linked to the ancestral (original) strain of the virus, with decreasing risk seen for later variants, including Omicron. However, because Omicron was so prevalent, it was responsible for nearly 79% of long COVID cases.

Additionally, the severity of the initial illness also played a major role. Individuals who had severe acute COVID-19 episodes, especially those hospitalized or reporting multiple severe symptoms, were more likely to suffer long-term effects. Conversely, the risk was less than 5% for those with mild or moderate illness, whether it was a first infection or reinfection.

Among those still experiencing symptoms at the time of the survey, 43% had moderate and 33% had severe long COVID, based on self-reported symptom intensity. These individuals reported a higher number of symptoms, with many experiencing fatigue, cognitive issues like brain fog, post-exertional malaise, and shortness of breath. Some cases persisted for over a year, and a small fraction lasted three years or more. The researchers also observed seven distinct groups of symptoms (symptom clusters), with systemic, neurocognitive, and respiratory problems being most common in severe cases.

The survey’s low response rate was a limitation, as it may have overestimated long COVID prevalence, though a validation study supported the main findings. The researchers also acknowledged that the reliance on self-reported data may have introduced recall bias and that the study population was predominantly middle-aged, white, and female, which may affect generalizability.

High vaccination rates in the cohort (with 78.6% having received three or more doses) may have contributed to the lower risk of long COVID following Omicron infections.

Conclusions

Overall, the study confirmed that long COVID is a persistent and serious health concern, especially after initial infections and severe cases. While reinfections pose a lower individual risk, their cumulative impact remains significant due to ongoing virus circulation.

As frontline workers continue to face exposure, understanding and addressing long COVID’s functional consequences is crucial. The findings emphasize that future health policies must factor in both prevention and long-term support for those affected.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.