Long COVID more common in pre-delta period compared with delta, omicron
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Prolonged COVID-19 symptoms, including severe fatigue, were more common among patients infected during the pre-delta period compared with the later delta and omicron periods, researchers found.
However, the differences were no longer present after accounting for vaccination, suggesting “a potential beneficial effect of vaccination on the risk of developing long-term symptoms,” the researchers wrote.
“This study was part of a larger, prospective trial called INSPIRE [which is] a prospective, longitudinal study across eight major medical centers in the U.S. following symptomatic patients with and without COVID-19 for up to 18 months to best understand their lived experiences,” Michael Gottlieb, MD, associate professor of emergency medicine and director of the Emergency Ultrasound Division at the Rush University Medical Center, told Healio.
To date, INSPIRE has enrolled 6,000 patients who complete surveys every 3 months to help researchers better understand symptoms, quality-of-life measures, health care utilization and a variety of other long-term impacts of COVID-19.
“As frontline emergency physicians and researchers, we have seen differences in symptoms across the variants,” Gottlieb said. “However, much of the focus on variant research was on the initial presenting symptoms.”
Because a percentage of patients will experience long COVID after their initial infection, Gottlieb explained that he and colleagues would like to better understand if these longer term symptoms would differ by variant — specifically, pre-delta, delta and omicron — as was seen with the initial symptoms, including fatigue, which he said is a common and “particularly concerning” long-term symptom.
Gottlieb and colleagues performed a multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms and presence of three or more total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis.
The researchers performed a sensitivity analysis using a 90% or more dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for sociodemographic characteristics, baseline health and vaccine status.
In total, 3,223 patients — 2,402 COVID-19 positive and 821 COVID-10 negative — were included in the study. Among those who were COVID-19 positive, 463 (19.3%) were pre-delta, 1,198 (49.9%) during delta and 741 (30.8%) during omicron.
The analysis showed that prolonged severe fatigue was highest in the pre-delta COVID-19-positive cohort compared with the delta and omicron cohorts (16.7%, 11.5% and 12.3%, respectively; P = .017), as was presence of three or more other prolonged symptoms (28.4%, 21.7% and 16%, respectively; P < .001).
Additionally, significantly more participants in the pre-delta group reported prolonged symptoms at 3 months compared with those in the delta and omicron groups (52.6%, 41.5% and 41.5%, respectively; P < .001).
Specific symptoms recorded commonly among pre-delta cases included higher rate of fever, chills, loss of taste/smell, chest pains, shortness of breath, nausea and vomiting, diarrhea and muscle and joint aches compared with delta and omicron.
Multivariable models showed that there was no difference in severe fatigue between variants, although they found that there were decreased odds of having three or more symptoms during the omicron period compared with other variants.
Gottlieb explained that this did not account for the impact of vaccination, which became more common as the pandemic evolved, and that once the team accounted for vaccination, they found that there was no longer a significant difference in total symptoms or fatigue severity across variants, suggesting a beneficial impact of vaccination.
“Some prolonged symptoms may differ across variants. However, vaccination appears to reduce both the number of symptoms and fatigue severity across variants,” Gottlieb said. “Despite this, persistent symptoms were common with approximately one in eight participants reporting persistent severe fatigue at 3 months.”
[Editor’s note: This story was updated to emphasize that the differences in rate of long-term symptoms were no longer significant after the researchers adjusted for vaccination status.]
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