Today in BMC Medicine, researchers in Catalonia, Spain, estimate that 23% of adult COVID-19 survivors develop long COVID, with 56% of them—or one in eight (13%) of those infected—still experiencing symptoms at 2 years.
The team evaluated 2,764 COVID-19 survivors from a population-based cohort established before the pandemic and followed up in 2020, 2021, and 2023 for concentrations of immunoglobulin (Ig) G antibodies against SARS-CoV-2 and clinical, vaccination, sociodemographic, and lifestyle factors. Symptoms were derived from patient questionnaires and electronic health records, and participants gave blood samples at study visits.
The 647 long-COVID patients were compared with 2,117 infected controls without long-term symptoms.
"The mechanisms leading to long-COVID are multiple and still unclear," the investigators wrote. "Identifying subtypes and disease courses over time may help disentangle these mechanisms."
Three subtypes identified
From 2021 to 2023, 23% of participants developed long-COVID symptoms, with 56% of those infected in 2021 reporting symptoms for 2 years. The researchers identified three long-COVID subtypes: mild neuromuscular (51.6%), mild respiratory (20.6%), and severe multi-organ (27.8%), the latter of which carried the highest risk of persistent symptoms (relative risk [RR], 1.61).
The most common long-COVID symptoms were neurologic (63%), muscular (39%), respiratory (28%), and psychological and psychiatric (21%). Women were more likely than men to report neurologic and muscular symptoms, while respiratory symptoms were more common in men.
Long-COVID patients first infected during the Omicron period had similar but fewer long-term symptoms than those infected before that time, which the researchers said could be due to milder infections or greater general immunity to the virus.
Risk factors included female sex, age younger than 50 years, low socioeconomic status, severe COVID-19 infection, high pre-vaccination IgG levels, obesity, and chronic illness, especially asthma or chronic obstructive pulmonary disease (COPD) and depression/anxiety. People with mild or moderate COVID-19 had more than three times the risk (RR, 3.10) of lingering symptoms as those with no symptoms, and those with severe infection were nearly 10 times more likely (RR, 9.88).
Vaccination protective
Protective factors were vaccination before infection or within 3 months after infection, Omicron variant infection, greater level of physical activity, and sleeping for 6 to 8 hours a night. "The discovery that pre-infection vaccination confers a protective effect on long-COVID, even when accounting for COVID-19 severity, suggests improved infection control and immune response modulation by vaccines," the study authors wrote.
