COVID-19 reinfection doubles the risk of death

COVID-19 reinfection doubles the risk of death and triples the risk of hospitalization, with post-acute sequelae in the pulmonary and extra-pulmonary organ systems, in a new study.

Vaccination and booster status did not improve survival or hospitalization rates among people who had COVID-19 more than once,  said study author Dr Ziyad Al-Aly, a clinical epidemiologist at Washington University School of Medicine in St. Louis and the Veterans Affairs Saint Louis Health Care System in St Louis, Missouri, US.

“Reinfection with COVID-19 also increases the risk of both acute outcomes and long COVID,” he added. “This was evident in unvaccinated, vaccinated, and boosted individuals.”

“Without ambiguity, our research showed that getting COVID-19 infection a second, third, or fourth time contributes to additional health risks in the first 30 days after infection and in the long COVID phase,” reported Al-Aly.

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, and heart and brain disorders. The risks were most pronounced in the acute phase but persisted for 6 months.

To what extent does reinfection add to COVID-19 risk?

The researchers analysed data from the US Department of Veterans Affairs involving 443,588 people who had COVID-19 for the first time, 40,947 who had contracted the disease twice or thrice, and 5.3 million without COVID-19 infection who served as controls. [Nat Med 2022;28: 2398–2405]

Overall, they found that people who had COVID-19 reinfections were twice as likely to die (hazard ratio [HR], 2.17, 95 percent confidence interval [CI], 1.93–2.45) and three times more likely to be hospitalized (HR, 3.32, 95 percent CI, 3.13–3.51) than those without reinfection.

Additionally, individuals with repeat infections were more than thrice as likely to develop pulmonary (HR, 3.54), kidney (HR, 3.55), cardiovascular (HR, 3.02), and coagulation and haematological disorders (HR, 3.10). They were twice more likely to have fatigue (HR, 2.33), gastrointestinal (HR, 2.48), and mental health disorders (HR, 2.14) than patients who had been infected only once.

Additionally, these individuals were at increased risk for diabetes (HR, 1.70), musculoskeletal (HR, 1.64), and neurological disorders (HR, 1.60).

The risks and excess burdens of all-cause death, hospitalization, and at least one sequelae in the post-acute phase gradually attenuated over time but remained evident 6 months after reinfection. The same was true for sequelae by organ system.

Cumulative risks and burden of reinfections

The risk appeared to increase with each infection. Compared with the noninfected group, those who had one infection had an increased risk of at least one sequelae (HR, 1.37). The risk was higher in those with two infections (HR, 2.07) and highest in those with three or more infections (HR, 2.35).

“Our findings highlight the clinical consequences of reinfection,” said Al-Aly. “If you’ve had two COVID-19 infections, it’s better to avoid a third. And if you’ve had three infections, it’s best to avoid a fourth.”

He said the results have broad public health implications. “These tell us that strategies to prevent or reduce the risk of reinfection should be implemented. People should be aware of the risks and practice vigilance to reduce their risk of infection or reinfection with SARS-CoV-2.”

The findings may not apply to the general population as the data primarily came from White men. Still, limiting exposure to the virus is particularly important, said Al-Aly. “People should do their best to prevent repeat infections by masking, getting eligible boosters, or staying home when sick.”