CD4 and CD8 Lymphocyte Counts as Surrogate Early Markers for Progression in SARS-CoV-2 Pneumonia: A Prospective Study

Abstract

Background: COVID-19 pathophysiology and the predictive factors involved are not fully understood, but lymphocytes dysregulation appears to play a role. This paper aims to evaluate lymphocyte subsets in the pathophysiology of COVID-19 and as predictive factors for severe disease. Patient and methods: A prospective cohort study of patients with SARS-CoV-2 bilateral pneumonia recruited at hospital admission. Demographics, medical history, and data regarding SARS-CoV-2 infection were recorded. Patients systematically underwent complete laboratory tests, including parameters related to COVID-19 as well as lymphocyte subsets study at the time of admission. Severe disease criteria were established at admission, and patients were classified on remote follow-up according to disease evolution. Linear regression models were used to assess associations with disease evolution, and Receiver Operating Characteristic (ROC) and the corresponding Area Under the Curve (AUC) were used to evaluate predictive values. Results: Patients with critical COVID-19 showed a decrease in CD3+CD4+ T cells count compared to non-critical (278 (485 IQR) vs. 545 (322 IQR)), a decrease in median CD4+/CD8+ ratio (1.7, (1.7 IQR) vs. 3.1 (2.4 IQR)), and a decrease in median CD4+MFI (21,820 (4491 IQR) vs. 26,259 (3256 IQR)), which persisted after adjustment. CD3+CD8+ T cells count had a high correlation with time to hospital discharge (PC = −0.700 (−0.931, −0.066)). ROC curves for predictive value showed lymphocyte subsets achieving the best performances, specifically CD3+CD4+ T cells (AUC = 0.756), CD4+/CD8+ ratio (AUC = 0.767), and CD4+MFI (AUC = 0.848). Conclusions: A predictive value and treatment considerations for lymphocyte subsets are suggested, especially for CD3CD4+ T cells. Lymphocyte subsets determination at hospital admission is recommended.

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

“…A low or inverted CD4/CD8 ratio is considered an immune risk phenotype associated with altered immune function, immunosenescence and chronic inflammation in both HIV positive and negative populations (Appay and Sauce 2008; Serrano-Villar et al 2014a; Serrano-Villar et al 2014c). Due to its predictive power for adverse clinical outcomes in HIV infection and in the ageing general population (Helleberg et al 2015; Serrano-Villar et al 2014c; Serrano-Villar et al 2014b), including its potential role as a prognostic factor of COVID-19 disease severity (Calvet et al 2020), the CD4:CD8 ratio could represent an additional tool for risk stratification of PLWH. The relationship between naïve CD4 T cells, CD4:CD8 ratio and magnitude of SARS-CoV-2-specific responses in our cohort highlights the dependency between new antigen-specific responses and the available pool of naïve lymphocytes.…”

“…Burgeoning evidence supports a role for CD4 T cells in the control and resolution of acute SARS-CoV-2 infection (Oja et al 2020; Rydyznski Moderbacher et al 2020; Tan et al 2021), in addition to providing CD8 T cell and B cell help for long-term immunity (Crotty 2015; Laidlaw et al 2016). Any pre-existing CD4 T cell depletion in PLWH, as described in patients with haematological malignancy (Annika Fendler 2020), could therefore be a potential driver of dysregulated immunity to SARS-CoV-2, hampering antiviral responses (Calvet et al 2020) and development of immunological memory.…”

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

“…A low or inverted CD4/CD8 ratio is considered an immune risk phenotype associated with altered immune function, immunosenescence and chronic inflammation in both HIV positive and negative populations [68][69][70] . Due to its predictive power for adverse clinical outcomes in HIV infection and in the ageing general population 70-72 , including its potential role as a prognostic factor of COVID-19 disease severity 24 priming and poorly coordinated early and subsequent memory immune responses to SARS-CoV-2. Our cohort and interim analysis does not represent the entire spectrum of immune dysfunction, which we will continue to probe through ongoing recruitment to test these relationships more rigorously.…”

“…A low or inverted CD4/CD8 ratio is considered an immune risk phenotype associated with altered immune function, immunosenescence and chronic inflammation in both HIV positive and negative populations [68][69][70] . Due to its predictive power for adverse clinical outcomes in HIV infection and in the ageing general population [70][71][72] , including its potential role as a prognostic factor of COVID-19 disease severity 24 , the CD4:CD8 ratio could represent an additional tool for risk stratification of PLWH. The relationship between naïve CD4 T cells, CD4:CD8 ratio and magnitude of SARS-CoV-2-specific responses in our cohort highlights the dependency between new antigen-specific responses and the available pool of naïve lymphocytes.…”

“…Burgeoning evidence supports a role for CD4 T cells in the control and resolution of acute SARS-CoV-2 infection [18][19][20] , in addition to providing CD8 T cell and B cell help for long-term immunity [21][22] . Any pre-existing CD4 T cell depletion in PLWH, as described in patients with haematological malignancy 23 , could therefore be a potential driver of dysregulated immunity to SARS-CoV-2, hampering antiviral responses 24 and development of immunological memory.…”