Jiang et al. (2025)
- Authors: Zhengqi Jiang, Tichao Shan, Yucan Li, Feng Han, Bin Feng, Xinyu Zhen, Haibo Ni, Jian Peng, Miao Xu.
- Institutes: Department of Hematology, Ningbo First Hospital, Ningbo University; State Key Laboratory for Pathogenesis, Prevention and Treatment of Central Asian High Incidence Diseases.
- Publisher: International Journal of Infectious Diseases
- Link: DOI
Summary
This study provides high-volume evidence supporting the theory that COVID-19 can leave the immune system in a weakened state for nearly two years. For patients with ME/CFS and Long COVID, this research is significant because it identifies a clear, measurable biological abnormality—low lymphocyte counts—that aligns with symptoms of chronic fatigue and increased susceptibility to other infections. The finding that heart disease patients are particularly affected suggests that pre-existing health issues may compound the immune damage caused by the virus. While more work is needed to see if this “immune scar” is permanent, the study offers a concrete marker that could eventually help in diagnosing post-viral conditions or measuring the success of future immune-restoring treatments.
What was researched?
This study investigated whether key immune cells, known as lymphocyte subsets (including T cells, B cells, and NK cells), remain depleted in the blood long after the initial phase of a SARS-CoV-2 infection. The researchers tracked these levels over 20 months to see if a mass infection wave causes a temporary dip or a lasting “scar” on the human immune system.
Why was it researched?
It is well-established that lymphocytes drop significantly during the acute phase of COVID-19, but there has been conflicting evidence regarding how quickly these levels recover. With millions of people suffering from Long COVID, scientists wanted to determine if persistent immune cell depletion could be a biological driver of chronic symptoms and whether certain groups, such as those with heart disease, are more vulnerable to long-term immune compromise.
How was it researched?
This was a large-scale retrospective cohort study that analyzed laboratory data from 40,537 individuals at a major hospital in China. The researchers compared lymphocyte counts across three timeframes: a pre-COVID baseline (January 2021 – November 2022), a mass infection period (December 2022 – February 2023), and a post-COVID follow-up period (March 2023 – August 2024). They used statistical modeling to track immune recovery over 20 months and conducted specialized subgroup analyses for patients with pre-existing cardiovascular disease (CVD).
What has been found?
The study found that a single wave of mass infection led to a significant and persistent reduction in nearly all lymphocyte subsets. Even 20 months after the initial exposure, CD8+ T cells (which are critical for killing virally infected cells) remained 9.9% below their pre-pandemic baseline. The impact was most severe in patients with cardiovascular disease, whose total T-cell counts dropped by 72.9% and showed almost no signs of recovery over the two-year period. Furthermore, the study noted that males and older adults experienced significantly slower immune restoration compared to other groups.
Discussion
The authors highlight that these findings redefine SARS-CoV-2 as a condition that can induce a state of “long-lasting immune compromise” in a significant portion of the population. They discuss potential causes, such as the virus persisting in tissues or causing exhaustion in the bone marrow where these cells are produced. A noted limitation is that the data comes from patients who visited a hospital, which might not perfectly represent the entire healthy population, and some critics have pointed out that while the drops are statistically significant, many patients’ counts may still fall within the broad “normal” clinical range.
Conclusion & Future Work
The researchers conclude that the sustained reduction in lymphocytes is a key immunologic feature of the post-COVID landscape and may contribute to the pathogenesis of Long COVID. They call for personalized clinical care for those showing persistent lymphopenia, especially those with pre-existing conditions. Future research is needed to determine if these immune changes eventually reverse on their own or if specific immunotherapies are required to help the body rebuild its defenses.