Dynamic immune response and its influencing factors in COVID-19 patients with non-alcoholic fatty liver disease: A cohort study

Abstract

BACKGROUND

Dynamic alterations in lymphocyte subsets demonstrate significant correlations with clinical disease severity in patients with coronavirus disease 2019 (COVID-19). As the most prevalent chronic liver disease globally, non-alcoholic fatty liver disease (NAFLD) exhibits distinct chronic inflammatory and immunometabolic disturbances that may substantially affect immune response patterns in COVID-19 patients. Nevertheless, the characteristics of lymphocyte subset dynamics and their clinical implications in COVID-19-NAFLD remain to be fully elucidated.

AIM

To characterize the dynamic changes in lymphocyte subsets among COVID-19 patients with NAFLD, in order to delineate their immunological profiles and inform clinical management strategies.

METHODS

The cohort study compared lymphocyte subpopulations in 858 COVID-19 patients and 670 COVID-19-NAFLD patients at admission, discharge, and 2-week/4-week post-discharge follow-ups.

RESULTS

Compared to COVID-19 patients without NAFLD, NAFLD-comorbid patients demonstrated persistently elevated CD3+CD4+ counts as well as lymphocyte counts and percentages at admission and at the 2-week and 4-week follow-ups post-discharge (all P < 0.05). Among COVID-19-NAFLD patients, those aged ≥ 60 years had significantly lower CD3+ counts, CD3+CD4+ counts, CD3+CD8+ counts, lymphocyte counts and percentages, and CD19+ counts and percentages at all assessed time points (all P < 0.05); significant liver fibrosis correlated with reduced CD3+CD4+ counts, CD3+CD8+ counts, and lymphocyte counts and percentages across all time points (all P < 0.05); multimorbidity (≥ 3 comorbidities) exacerbated immune imbalance, marked by elevated CD3+CD4+ percentages and CD56+ counts at admission, increased CD3+CD4+ counts, lymphocyte counts, and CD19+ counts and percentages at discharge, as well as sustained increases in CD3+CD4+ counts at the 2-week follow-up and higher CD3+CD4+ percentages at the 4-week post-discharge follow-up (all P < 0.05); and obesity and elevated liver enzymes were independently linked to higher CD3+CD4+ counts, CD19+ counts, and lymphocyte counts at all post-admission evaluations (from discharge through the 4-week follow-up) (all P < 0.05).

CONCLUSION

Age, liver fibrosis, comorbidities, obesity, liver enzyme abnormalities, vaccination status, low-density lipoprotein cholesterol, and hemoglobin A1c significantly modulate immune responses in COVID-19-NAFLD patients, warranting targeted clinical attention. Furthermore, patients with uncomplicated NAFLD (including lean NAFLD) also require particular clinical attention to mitigate risks of immune imbalance.

Keywords: COVID-19; Non-alcoholic fatty liver disease; Lymphocyte subsets; Dynamic immune response; Risk factors

Core Tip: This study reveals that coronavirus disease 2019 patients with non-alcoholic fatty liver disease (NAFLD) exhibit prolonged immune imbalance. Key risk factors—including age ≥ 60 years, significant liver fibrosis, multimorbidity (≥ 3 conditions), obesity, elevated liver enzymes, elevated low-density lipoprotein cholesterol, and elevated hemoglobin A1c—worsen immune imbalance. Notably, even lean NAFLD patients show persistent immune disturbances. These findings highlight the need for tailored clinical monitoring in coronavirus disease 2019-NAFLD patients, particularly for older adults, those with metabolic dysfunction, or those with advanced liver disease, to mitigate long-term immunological complications.