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5MinuteConsult Journal Club

Once is Too Much, and More is Worse


Nature Medicine (28); | November 2022 | 2398–2405

Study Summary

This observational study using the US Department of Veterans Affairs’ healthcare database compared individuals with one SARS-CoV-2 infection (n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control (n = 5,334,729).

Reinfection was associated with an additional risk of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae (pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders) compared to those who did not have a repeat infection.

The risks were greatest in the acute phase of illness but persisted at 6 months. Compared to noninfected controls, risks of repeat infection increased according to the number of infections. The more infections, the greater the risk. Additionally, these risks were present regardless of vaccination status.


Wear a mask and stay away from others, especially indoors. Really.

SARS-CoV-2 infection increases your risk for adverse events. But repeat infection, even in vaccinated, comes with risks. Winter moves us all indoors, and with COVID, influenza, RSV and now some unnamed infection in the Midwest seeming to infect children, everyone’s risks will go up. This study should scare us all. The US has the highest COVID mortality in the industrialized world. The highest.

I continue to receive push back from folks who have vaccine fatigue and maybe 10% who continue to refuse vaccination. Not that logic helps, but if someone is on the fence, use this data to further encourage them to get a booster, stay away from others, and wear a mask.

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