Individuals With Higher CD4/CD8 Ratio Exhibit Increased Risk of Acute Respiratory Distress Syndrome and In-Hospital Mortality During Acute SARS-CoV-2 Infection

Ana Pascual-Dapena; Juan José Chillaron; Gemma Llauradó; Isabel Arnau-Barres; Juana Flores; Inmaculada Lopez-Montesinos; Luisa Sorlí; Juan Luis Martínez-Pérez; Silvia Gómez-Zorrilla; Juan Du; Natalia García-Giralt; Robert Güerri-Fernández

doi:10.3389/fmed.2022.924267

Individuals With Higher CD4/CD8 Ratio Exhibit Increased Risk of Acute Respiratory Distress Syndrome and In-Hospital Mortality During Acute SARS-CoV-2 Infection

Front Med (Lausanne). 2022 Jun 23:9:924267. doi: 10.3389/fmed.2022.924267. eCollection 2022.

Authors

Affiliations

¹ Medicine and Life Sciences Department, Pompeu Fabra University, Barcelona, Spain.
² Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
³ Endocrinology Department, Hospital del Mar Institute of Medical Research, Barcelona, Spain.
⁴ Geriatrics Department, Hospital del Mar Institute of Medical Research, Barcelona, Spain.
⁵ Infectious Diseases Department, Hospital del Mar Institute of Medical Research, Barcelona, Spain.
⁶ Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Ciberinfecc, Instituto de Salud Carlos III, Madrid, Spain.

Abstract

Background: CD4/CD8 ratio has been used as a quantitative prognostic risk factor in patients with viral infections. This study aims to assess the association between in-hospital mortality and at admission CD4/CD8 ratio among individuals with acute SARS-CoV-2 infection.

Methods: This is a longitudinal cohort study with data of all consecutive patients admitted to the COVID-19 unit at Hospital del Mar, Barcelona, Spain for ≥48 h between March to May 2020. The CD4+ CD8+ T-cell subset differentiation was assessed by flow cytometry at admission as well as a complete blood test. Patients were classified according to CD4/CD8 ratio tertiles. The primary outcome was in-hospital mortality and the secondary outcome was acute respiratory distress (ARDS).

Results: A total of 338 patients were included in the cohort. A high CD4/CD8 ratio (third tertile) was associated with a higher in-hospital mortality [adjusted Cox model hazard ratio (HR) 4.68 (95%CI 1.56-14.04, p = 0.006), reference: second tertile HR 1]. Similarly, a high CD4/CD8 ratio (third tertile) was associated with a higher incidence of ARDS [adjusted logistic regression model OR 1.97 (95%CI 1.11-3.55, p = 0.022) reference: second tertile HR 1]. There was a trend of higher in-hospital mortality and incidence of ARDS in patients within the first tertile of CD4/CD8 ratio compared with the second one, but the difference was not significant. No associations were found with total lymphocyte count or inflammatory parameters, including D-dimer.

Conclusion: CD4/CD8 ratio is a prognostic factor for the severity of COVID-19, reflecting the negative impact on prognosis of those individuals whose immune response has abnormal CD8+ T-cell expansion during the early response to the infection.

Keywords: ARDS; CD4/CD8 ratio; SARS-CoV-2; mortality; prognose.