#18,839
For more than three years now, many governments around the world - in an attempt to `move beyond the pandemic' - have minimized the ongoing impacts of COVID by ending surveillance and the reporting of numbers of associated hospitalizations or deaths.As a result, most people now regard COVID as little more than a `bad cold'. COVID vaccine uptake has dropped precipitously, and mask wearing in public has all but disappeared.
At the same time, tens of millions of people have developed `Long COVID', which can range from mild to debilitating. Since there is no standardized case definition for Long COVID (see JAMA Network) - we often see inconsistent data from studies - and many patients end up untreated.
Based on limited data, however, the WHO estimates that 1 in 6 people who contract COVID will develop some type of `Long COVID'. Globally, that suggests > 400 million people, and > 20 million in the United States.
While many will see some improvement in their symptoms over time, others face chronic, and often debilitating, lifelong illness. Studies have suggested COVID sequelae could include increased cardiac risks, increased new onset hypertension, an increased risk of developing diabetes, strokes, and kidney disease/injury.
There may also be other, longer-range health impacts from COVID, that have yet to be elucidated (see BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19).
The WHO states:
Anyone who was infected with SARS-CoV-2 can develop post COVID-19 condition. Some people have higher risk. These include women, older adults, smokers, those who are overweight or obese or have pre-existing chronic health problems.
Repeated infections and severe COVID-19 needing hospitalization or ICU admission also increase the risk (4). We see higher numbers of post COVID-19 condition sufferers among people with disabilities, and where health disparity and access to health care is a problem (5).
The CDC states:
Most people with Long COVID experience symptoms days after first learning they had COVID-19, but some people who later develop Long COVID do not know when they were infected. People can be reinfected with SARS-CoV-2 multiple times. Each time a person is infected with SARS-CoV-2, they have a risk of developing Long COVID. 12 Long COVID symptoms and conditions can emerge, persist, resolve, and reemerge over weeks and months. 345 These symptoms and conditions can range from mild to severe, may require comprehensive care, and can even result in a disability.
While each COVID infection is another opportunity for an individual to develop Long COVID there has been some debate over whether that risk increases with each bout of illness.
In January of 2023, the AMA released a statement (see What doctors wish patients knew about COVID-19 reinfection) calling reinfection `problematic' and equating it to `. . . playing Russian roulette" with the virus.
A 2023 study - conducted after the emergence of Omicron (see Risk of New-Onset Long COVID Following Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2) found:
The risk of new-onset long COVID after a second SARS-CoV-2 infection is lower than that after a first infection for persons aged ≥16 years, though there is no evidence of a difference in risk for those <16 years.
Earlier this year, CIDRAP reported a similar finding (see Data suggest COVID-19 reinfections less likely to cause long COVID), but with the caveat:
The cumulative risk of long COVID increased with the number of reported COVID-19 infections, rising from 13.7% (95% confidence interval [CI], 13.1% to 14.4%) for a single infection to 37.0% (95% CI, 33.0% to 40.9%) for three infections in the online survey, and from 11.8% (a single infection) to 29.5% (≥3 infections) in the telephone survey, according to the authors.Nebulous or inconsistent `Long COVID' case definitions, the abandonment of serious surveillance, testing, and reporting by most governments, and the resultant trivialization of COVID infection by society, are all obstacles to quantifying the risks.
But today we have a preprint (yet to be peer-reviewed) which describes a large observational analysis using the data from National Clinical Cohort Collaborative (N3C)/RECOVER initiative, that finds that reinfection resulted in a 35% higher risk of Long COVID (compared to a single infection).
Incidence of Long COVID Following Reinfection with COVID-19
M Daniel Brannock, Emily Hadley, Alexander Preiss, Megan L Fitzgerald, Nita Jain, Emily Taylor, Andrew Wylam, Yun J Yoo, Elaine Hill, Richard A Moffitt, N3C Consortium, RECOVER Consortium
doi: https://doi.org/10.1101/2025.08.12.25333155
This article is a preprint and has not been certified by peer review
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Abstract
Background COVID-19 reinfections have emerged as a critical concern, particularly in relation to post-acute sequelae of SARS-CoV-2 infection, commonly known as long COVID. Long COVID is known to manifest diverse, debilitating symptoms across all demographics. Limited studies have investigated the causal relationship of COVID-19 reinfections and long COVID.Methods We leveraged demographically diverse electronic health records from the COVID-19 enclave of the National Clinical Cohort Collaborative, part of the RECOVER initiative, to create a matched cohort of reinfected and control adults. All participants had at least one documented COVID-19 infection. We used one-to-one coarsened exact matching on sex, race/ethnicity, age, healthcare utilization, existing comorbidities, site of care, and the timing and severity of first infection.
Index dates were assigned to each matched pair as the date of reinfection for the reinfected case. Long COVID was defined using a machine learning computable phenotype trained on clinically diagnosed long COVID cases. Cumulative incidence one year after index was calculated using an Aalen-Johansen estimator. Risk ratios were calculated by taking the ratio of long COVID incidence among reinfected and control cases.Results We found that reinfection resulted in a significantly higher risk of long COVID compared to not being reinfected (risk ratio, 1.35, 95% CI, 1.32-1.39; risk difference, 0.029, 95% CI, 0.027-0.031). This effect was consistent across most stratifications.Conclusions We found that COVID-19 reinfection resulted in a roughly 35% increase in the incidence of long COVID in a matched cohort using observational electronic health records.
(SNIP)
In conclusion, we found that reinfections lead to a roughly 35% (95% CI, 32-39%) increase in the risk of long COVID as compared to not having a documented reinfection. The relative effect was consistent across most strata of most of our matching criteria, including sex and timing and severity of first infection. There were differences in relative risk across different age and CCI strata.
In a vaccination subanalysis, we found that those vaccinated between first infection and index date experienced a smaller increase in the relative risk of long COVID resulting from reinfection as compared to those vaccinated only prior to their first infection.
While it is true most people will recover from acute COVID infection without sustaining long-term damage - it appears that the more times one tempts fate - the more likely they are to suffer real consequences.
And that not only presents individual health challenges, but substantial societal burdens as well.
Despite proven ways to reduce the risk of reinfection (COVID vaccines, wearing face mask in public, avoiding indoor crowds, etc.), few appear interested. Today - despite ample evidence to the contrary - many people are more inclined to blame the vaccine for their ills, than the virus.
When it comes to prevention, everyone needs to make their own risk/reward analysis. I've made mine (staying current with the COVID vaccine, wearing a KN95 in crowded indoor venues, etc.).
A few past studies that might be of interest to those who are still undecided, include:
Brain, Behavior & Immunity: COVID-19 may Enduringly Impact Cognitive Performance and Brain Haemodynamics in Undergraduate Students
ECDC Rapid Review: Does COVID-19 Vaccination Reduce the Risk and Duration of Post COVID-19 Condition?
Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks