COVID-19: Risk of death and long COVID following SARS-CoV-2 infection post-vaccination

People who get COVID-19 after vaccination can still experience symptoms associated with long COVID 6 months after diagnosis, according to a study of over 13 million veterans in the United States published in Nature Medicine. These risks and those for death are lower than they are in unvaccinated people with COVID-19, but are higher than they are in those with seasonal influenza. The research suggests that continued optimization of strategies for the prevention of infection, as well as developing care pathways for long COVID, are needed.

Symptoms of long COVID after infection with SARS-CoV-2 have been documented. However, whether these are also associated with infection with SARS-CoV-2 following vaccination — also known as breakthrough SARS-CoV-2 infection (BTI) — is currently unknown.

Ziyad Al-Aly and colleagues investigated the long- and short-term risks associated with BTI in vaccinated people (33,940 in total) — defined as those who had completed a full vaccination program with one dose of the Janssen vaccine or two doses of the Moderna or Pfizer–BioNTech vaccines — versus several control groups (13,335,133 people in total), using national healthcare data from the US Department of Veteran Affairs. The authors estimate that vaccinated people who experience BTI have a higher risk of death (an additional 13.36 deaths per 1,000 people) and of developing associated symptoms of long COVID, such as pulmonary and cardiovascular disorders (122.22 more people per 1,000 experiencing at least one symptom), at 6 months after diagnosis. This is compared with those who had never recorded a positive test for SARS-CoV-2.

The authors found that during the first 30 days after diagnosis of COVID-19 as a result of BTI, for vaccinated people there were 10.99 fewer deaths per 1,000 people and 43.38 fewer people per 1,000 who experienced at least one symptom, compared with unvaccinated people who had been infected with SARS-CoV-2 (113,474 in total). In separate analyses, vaccinated people who were hospitalized with BTI (3,667 in total) had a higher estimated risk of death (43.58 more deaths per 1,000) and of developing symptoms of long COVID (87.59 additional people per 1,000 who experienced at least one symptom) in the first 30 days after diagnosis than that of people who were hospitalized with seasonal influenza (14,337 in total).

The authors conclude that these results could be used to help enhance strategies aimed at both preventing BTI and optimizing care for those who are affected.