Repeated SARS-CoV-2 infections increase risk of health problems in multiple organs

Since the start of the COVID-19 pandemic nearly three years ago, scientists have learned that an initial infection can lead to short- and long-term health risks affecting nearly every organ system in the body. They also determined that people can get COVID-19 a second or third time, despite acquiring natural antibodies after the first infection and vaccination and boosters.

Now, a new study from Washington University School of Medicine in St. Louis and the St. Louis Veterans Health Care System shows the health consequences of reinfection. Researchers have found that repeated SARS-CoV-2 infections contribute to a significant additional risk of adverse health conditions in multiple organ systems.

These outcomes include hospitalization; disorders affecting the lungs, heart, brain, blood, musculoskeletal and gastrointestinal systems of the body; and even death. Reinfection also contributes to diabetes, kidney disease, and mental health issues.

The results are published Nov. 10 in Nature Medicine.

Over the past few months, there has been an air of invincibility among people who have had COVID-19 or their shots and boosters, and especially among people who have had an infection and also received shots; some people have started referring to these people as having some sort of super-immunity to the virus. Unambiguously, our research has shown that acquiring an infection a second, third or fourth time contributes to additional health risks in the acute phase, i.e. the first 30 days after infection, and in the following months, i.e. the long COVID phase.

Ziyad Al-Aly, MD, lead author, clinical epidemiologist, Washington University School of Medicine in St. Louis

Additionally, the study indicated that the risk appears to increase with each infection. “This means that even if you have had two COVID-19 infections, it is better to avoid a third one,” Al-Aly said. “And if you’ve had three infections, it’s better to avoid the fourth one.”

Limiting exposure to the virus is particularly important as the United States heads into the winter months, with new variants emerging, mutating and already causing infections to rise in parts of the country, Al-Aly said. “People should do their best to prevent repeat infections by masking up, for example, getting all of their eligible boosters, staying home when sick. Also, getting the flu shot to prevent illness We really need to do our best to reduce the risk that we will have a double pandemic of COVID-19 and flu this winter.”

For this study, researchers analyzed about 5.8 million anonymized medical records in a database maintained by the US Department of Veterans Affairs, the nation’s largest integrated health care system. Patients represented multiple ages, races, and genders.

The researchers created a controlled data set of 5.3 million people who did not test positive for COVID-19 infection from March 1, 2020 to April 6, 2022. Using the same time period, the researchers also compiled a control group of more than 443,000 people who had tested positive for COVID-19 infection and another group of nearly 41,000 people who had two or more documented infections. In this latter group, most people had two or three infections, with a small number having had four infections and no one having had five or more.

Statistical modeling was used to examine the health risks of repeated COVID-19 infections within the first 30 days after contracting the virus and up to six months after.

The study considered COVID-19 variants such as delta, omicron and BA.5. Negative results occurred in the unvaccinated as well as in those who received injections prior to reinfection.

Overall, the researchers found that people with COVID-19 reinfections were twice as likely to die and three times more likely to be hospitalized than those without reinfection.

Additionally, people with repeat infections were 3.5 times more likely to develop lung problems, three times more likely to have heart problems, and 1.6 times more likely to have brain problems than patients who had been infected with the virus once.

“Our findings have broad implications for public health as they tell us that strategies to prevent or reduce the risk of reinfection should be implemented,” Al-Aly said. “Entering the winter season, people need to be aware of the risks and exercise vigilance to reduce their risk of infection or reinfection with SARS-CoV-2.”


Washington University School of Medicine in St. Louis

Journal reference:

Bowe, B. et al. (2022) Acute and post-acute sequelae associated with SARS-CoV-2 reinfection. Natural medicine.


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