New Long COVID studies demonstrate danger of breakthrough cases

About one in five adults who have COVID-19 will face a health condition potentially related to long-term symptoms, a new CDC study found.

Two new studies on Long COVID, published this week, provide an important reminder of the continued dangers this condition poses to people infected with the coronavirus—even after vaccination. Neither study provides wholly new information, but both are more comprehensive than many other U.S. papers on this condition as they’re based on large databases of electronic health records.

First: a team at the Veterans Affairs (VA) Health Care System in St. Louis, Missouri used the VA’s extensive health records database to study breakthrough COVID-19 cases. The VA database includes more than 1,400 healthcare facilities serving veterans across the country; this St. Louis team has previously used it to characterize Long COVID symptoms more broadly, to study long-term heart disease risks of COVID-19, and for other research.

In the new paper, published this week in Nature Medicine, the researchers put together a cohort of about 34,000 people who had breakthrough COVID-19 infections. They compared this group to larger control groups of people who hadn’t been infected and people who had been infected prior to vaccination, along with comparisons to the seasonal flu.

Vaccination does reduce the risk of Long COVID, the researchers found: people with breakthrough cases were 15% less likely to report Long COVID symptoms than those who were infected prior to vaccination. Breakthrough Long COVID patients were notably less likely to have blood clots and respiratory symptoms than non-breakthrough patients.

But a risk reduction of 15% is pretty minimal, compared to the protection that vaccination offers against COVID-related hospitalization and death. Moreover, for most Long COVID symptoms, patients who had breakthrough infections showed relatively little difference to those who had non-breakthroughs, the researchers found.

“Overall, the burden of death and disease experienced by people with breakthrough SARS-CoV-2 infection is not trivial,” lead researcher Dr. Ziyad Al-Aly wrote in a Twitter thread summarizing the study. That’s scientist speak for, “A breakthrough COVID-19 case can really fuck you up in the long term!” Later in his thread, Dr. Al-Aly advocated for additional public health measures—beyond simply vaccines—to reduce Long COVID risks.

And second: a paper from the CDC’s COVID-19 Emergency Response Team, published in the CDC’s Morbidity and Mortality Weekly Report (MMWR) last week, used electronic health records to examine overall Long COVID risk after an infection. These health records came from Cerner Real-World Data, a dataset including about 63.4 million records from over 100 health providers.

The CDC researchers identified about 353,000 adults who had received either a COVID-19 diagnosis or a positive test result between March 2020 and November 2021. They matched this group of COVID-19 patients with a larger cohort of people who hadn’t tested positive, then looked at the COVID-19 patients’ risks of developing further symptoms more than a month after they were diagnosed.

The findings are striking: About one in five COVID-19 survivors between the ages of 18 and 64 developed at least one “incident condition” (or, prolonged symptoms) that could be connected to their coronavirus infection. For COVID-19 survivors over age 65, that risk is one in four.

Among the patients who potentially developed Long COVID, common symptoms were blockages in the lungs and other respiratory issues. Seniors were also likely to develop neurological and mental health symptoms, and the CDC researchers warned that Long COVID in this older age group could be linked to an increased risk of strokes and neurocognitive conditions, such as Alzheimers.

In their paper, the CDC authors noted that patients represented in this health records database may not represent the U.S. overall, and that the methods used to identify possible Long COVID symptoms might be “biased toward a population that is seeking care.” Similar caveats apply to the VA study.

Still, both studies clearly show the risk of just “letting COVID-19 rip” through the U.S. population, even after widespread vaccination. Studies like these should be headlines in every news publication, warning people that COVID-19 is not as mild as many of our leaders would like us to believe.

Also, for journalists covering the pandemic: I highly recommend listening to this interview with Long COVID journalist and advocate Fiona Lowenstein, which aired on the WNYC show On the Media this weekend. (And I’m not just saying that because they plugged my recent story on the RECOVER study!) The Long COVID source list that Fiona and I collaborated on also continues to be a great resource for reporters covering this topic.

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