New Research Sheds Light on Link Between Leukocyte Count and Long COVID Symptom Severity

Leukocyte count, also known as white blood cell count, has been found to be an independent predictor of post-acute sequelae of SARS-CoV-2 infection (PASC) severity in older postmenopausal women, which could open the possibility of using this inflammatory marker as a predictor for COVID-19 symptom severity in a variety of patient populations.^1,2

Leukocytes, known as white blood cells, are a marker of inflammation. | Image Credit: © nobeastsofierce - stock.adobe.com

The new research findings, published in Menopause, shed light into the mechanisms behind the sustained COVID-19 symptoms many patients experience in the form of PASC, also called long COVID. Among the most common lingering symptoms—sometimes even months after initial diagnosis—include cognitive impairment and fatigue. Critically, older adults, especially women, are at the highest risk of developing long COVID.^1,2

Furthermore, the serious effects that PASC can have on multiple organ systems, despite being a primary respiratory disease, necessitate further research into what factors make certain adults more vulnerable to serious, sustained symptoms. In this new research, investigators utilized a secondary analysis of data from a Women’s Health Initiative survey conducted from 2021 to 2022 to better understand these preexisting factors; specifically, they investigated leukocyte count, which is a widely known and easily accessible clinical marker of systemic inflammation.²

In addition to survey data from the Women's Health Initiative, investigators utilized biomarker data from blood specimens collected during pre-pandemic enrollment in the initiative from 1993 to 1998. Results from a total of 1237 Women’s Health Initiative participants were included, and the study authors constructed multivariable regression models that controlled for key baseline characteristics to interpret the data. Patient PASC status was determined as per established criteria from the World Health Organization, according to the researchers.^1,2

Study results indicated that leukocyte count was strongly associated with PASC severity. After controlling for baseline characteristics, the investigators found that log_e-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, which was defined as the sum of all PASC symptoms. However, leukocyte count was not associated with the overall occurrence of PASC or PASC-related cognitive outcomes, constituting an important exception to the results.²

“As the authors highlight, PASC significantly affects quality of life, often leading to severe disability,” Monica Christmas, associate medical director for The Menopause Society, said in the news release. “This effect is particularly pronounced in women, who already experience higher rates of cognitive impairment after menopause.¹

These results demonstrate the potential of having a widely available predictor of long COVID severity available in the form of leukocyte count, which could transform diagnosis and treatment of the condition not only in older, postmenopausal women but in a variety of populations. It is critical for health care providers to monitor patients for persistent inflammation following a SARS-CoV-2 infection, and postmenopausal women—in addition to other eligible populations—should be prudent in efforts to prevent infection, such as receiving proper vaccination.¹

“By understanding underlying factors, we can better address these challenges and work to mitigate the cascade of symptoms that follow,” Christmas concluded.¹

REFERENCES

1. The Menopause Society. White blood cell count could predict severity of COVID-19 symptoms. EurekAlert!. News Release. Released January 29, 2025. Accessed March 7, 2025. https://www.eurekalert.org/news-releases/1071894

2. Ng TKS, Beydoun HA, Von A, et al. Pre-pandemic leukocyte count is associated with severity of post-acute sequelae of SARS-CoV-2 infection among older women in the Women's Health Initiative. Menopause. 2025;32(3):197-206. doi:10.1097/GME.0000000000002490