SARS-CoV-2 reinfection cumulates risk of all-cause mortality, hospitalization, and adverse health outcomes
It’s estimated that over half a billion people have been infected with SARS-CoV-2 at least once over the past few years – and almost seven million have died. SARS-CoV-2 infection is associated with increased risk of death, hospitalization, and damage to multiple organ systems – but does reinfection accumulate risk of acute and postacute sequelae?
Using the US Department of Veterans Affairs’ national healthcare database, researchers have created a cohort of over five million participants to compare and contrast health risks in individuals with one SARS-CoV-2 infection (no reinfection), reinfection (two or more infections), and non-infected controls (1).
Compared with people with only a single infection, reinfected individuals had greater risk of all-cause mortality, hospitalization, and adverse health outcomes – regardless of vaccination status before reinfection. The increased risk was most evident in the acute phase but persisted in the postacute phase – and, although gradually reducing over time, it was still present at six months post-infection.
What’s interesting – and disconcerting – is that increased risk was cumulatively correlated with the number of infections. (One previous infection carried the lowest risk, whereas the highest risk of mortality, hospitalization, and adverse outcomes was evident in people with three or more infections).
To the researchers’ knowledge, this is the first study to characterize both the short- and long-term health risks of SARS-CoV-2 reinfection; however, they acknowledge that data mostly came from older white males, making it less generalizable to populations of different age, gender, race, or ethnicity. Furthermore, the authors emphasize that the research was meant to study health risks associated with reinfection compared with non-reinfection – it therefore should not be used as an indicator of disease severity in individuals with second infection compared with the first. The study also does not compare the risks of reinfection between different variants or subvariants.
Despite being three years into the COVID-19 pandemic, there is evidently still a lot to learn. The researchers did not uncover the mechanisms behind increased risk from reinfection – could it be waning protection from the last immunity-conferring event? Perhaps Omicron’s blatant ignorance for immunity against reinfection and severity plays a role? Or maybe ill health caused by the initial infection increases the likelihood of additional health risks from reinfection? These are just some of the theories offered by the team.
The research adds to the growing body of evidence of risks associated with reinfection in the acute and post-acute phases, and highlights how public health policy should shift focus to the prevention of SARS-CoV-2 infection and reinfection.