Associations Between Lymphopenia and the Development/Recovery of Acute Kidney Injury Among Patients Hospitalized With Respiratory Virus Infections

Abstract

Rationale & Objective

Lymphopenia may have a potential mechanism on the development of acute kidney injury (AKI) after respiratory virus infection but has never been revealed. We aimed to investigate the relationship between lymphopenia and AKI in patients hospitalized with respiratory virus infections.

Study & Design

A single-center and retrospective cohort study.

Setting & Participants

Data were retrospectively collected from electronic medical records of patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, or other respiratory virus infections from 2016- 2023.

Exposure

Prolonged lymphopenia (<1.1 × 10⁹/L) was defined as continuous lymphopenia lasting for ≥1 day before AKI diagnosis. Serial measurements of serum creatinine levels and lymphocyte counts before AKI were collected.

Outcomes

AKI developed after infection was identified according to the KDIGO guideline.

Analytical Approach

Multivariable logistic regression models and Cox proportional regression models were conducted to evaluate associations between lymphopenia or blood count ratios and AKI.

Results

A total of 3,104 patients were analyzed, including 1,945 infected with SARS-CoV-2, 597 with influenza, and 472 with other respiratory virus infections. The AKI incidences were 18.0%, 23.3%, and 16.3%, respectively. Serum creatinine level was significantly negatively correlated with lymphocyte count in SARS-CoV-2 and influenza infections. Multivariable regression showed lymphopenia, especially prolonged lymphopenia, was significantly associated with AKI in all virus groups, especially in influenza. The risk magnitudes of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on admission for AKI varied by different viral infections. Lymphopenia or not was not associated with AKI stages or AKI recovery.

Limitations

The results were limited by the retrospective, single-center setting and the probability of underestimation of the prevalence of both lymphopenia and AKI.

Conclusions

Lymphopenia, especially prolonged lymphopenia, and neutrophil-to-lymphocyte ratio on admission were risk factors for AKI after respiratory virus infection, with the highest risk observed in patients with influenza.

Plain-Language Summary

Lymphopenia may play a role in acute kidney injury (AKI) after respiratory virus infections, but this link has not been well studied. Our research explored the relationship between lymphopenia and AKI in hospitalized patients with COVID-19, influenza, and other respiratory viruses. By reviewing medical records from 2016-2023, we found that prolonged lymphopenia was significantly associated with AKI, particularly in influenza cases. Blood count ratios also varied in their risk for AKI depending on the virus. These findings highlight the importance of monitoring immune cell levels in viral infections. Although our study offers new insights, its single-center and retrospective design may limit broader application. Future research is needed to confirm these results and explore potential interventions.