A simple blood test measuring white blood cell count could predict which patients are more likely to develop severe long COVID symptoms, according to new research published in the journal Menopause on January 29, 2025.
The study found that leukocyte count, a standard marker of inflammation, serves as an independent predictor of post-acute sequelae of SARS-CoV-2 infection (PASC) severity in older postmenopausal women. This discovery could potentially transform how healthcare providers identify and treat patients at risk for prolonged COVID-19 symptoms.
Researchers from the Rush Institute for Healthy Aging at Rush University Medical Center, led by Assistant Professor Ted Ng, analyzed data from 1,237 participants in the Women's Health Initiative survey conducted between 2021 and 2022. The team also utilized biomarker data from blood specimens collected during pre-pandemic enrollment in the initiative from 1993 to 1998.
"Our findings suggest that leukocyte count, a well-standardized, stable, widely available, and inexpensive clinical marker of inflammation, is an independent predictor of future PASC severity in postmenopausal women," the research team concluded.
Strong Association Between Leukocyte Count and Symptom Severity
The study results demonstrated a clear correlation between higher leukocyte counts and increased long COVID symptom severity. After controlling for baseline characteristics, the investigators found that loge-transformed leukocyte count (β = 0.27; 95% CI, 0.07–0.47; P = .009) and leukocyte count greater than or equal to 5.5 × 1,000 cells/µL (β = 0.13; 95% CI, 0.02–0.23; P = .02) were positively associated with PASC severity, defined as the sum of all PASC symptoms.
Notably, more than a third (36%) of the women in the study suffered from long COVID symptoms, with 75% experiencing two or more symptoms. Common manifestations included memory problems (13%), "brain fog" (12%), and difficulty thinking or concentrating (11%).
However, researchers found that leukocyte count was not associated with the overall occurrence of PASC or PASC-related cognitive outcomes, constituting an important exception to the results.
Implications for Understanding Long COVID Mechanisms
The findings align with a growing body of evidence suggesting that elevated inflammatory markers during or after COVID-19 infection are associated with subsequent long COVID severity and related symptoms.
One theory posits that the initial SARS-CoV-2 infection triggers significant inflammation that causes long-term damage to tissues and organs, resulting in persistent symptoms. Alternatively, the results might indicate that women with pre-existing low-level inflammation prior to COVID-19 infection could be more susceptible to developing severe long COVID.
"As the authors highlight, PASC significantly affects quality of life, often leading to severe disability," said Monica Christmas, associate medical director for The Menopause Society. "This effect is particularly pronounced in women, who already experience higher rates of cognitive impairment after menopause."
Clinical Significance and Future Directions
The discovery of leukocyte count as a potential predictor for long COVID severity has significant clinical implications. As a widely available and inexpensive test, it could help healthcare providers identify patients who may require closer monitoring and more aggressive treatment approaches following COVID-19 infection.
The researchers emphasized that it is critical for healthcare providers to monitor patients for persistent inflammation following SARS-CoV-2 infection. They also stressed the importance of preventive measures, particularly for vulnerable populations such as postmenopausal women.
"By understanding underlying factors, we can better address these challenges and work to mitigate the cascade of symptoms that follow," Christmas concluded.
Further research is needed to better understand the connections between long COVID and inflammation, and to verify the link between white blood cell counts and long COVID risk across different patient populations. The researchers also noted the need for additional studies to determine whether interventions targeting inflammation could potentially reduce the severity of long COVID symptoms.
This study represents an important step forward in identifying biomarkers that could help predict and manage long COVID, a condition that continues to affect millions worldwide and significantly impacts quality of life.
