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. 2021 Aug 9;11(8):603.
doi: 10.3390/membranes11080603.

Effects of Steroids and Tocilizumab on the Immune Response Profile of Patients with COVID-19-Associated ARDS Requiring or Not Veno-Venous Extracorporeal Membrane Oxygenation

Vito Fanelli  1   2 , Giorgia Montrucchio  1   2 , Gabriele Sales  2 , Umberto Simonetti  2 , Chiara Bonetto  2 , Francesca Rumbolo  3 , Giulio Mengozzi  3 , Rosario Urbino  2 , Costanza Pizzi  4 , Lorenzo Richiardi  4 , Paola Cappello  5   6 , Luca Brazzi  1   2
Affiliations

Effects of Steroids and Tocilizumab on the Immune Response Profile of Patients with COVID-19-Associated ARDS Requiring or Not Veno-Venous Extracorporeal Membrane Oxygenation

Vito Fanelli et al. Membranes (Basel). .

Abstract

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving rescue therapy in patients with Acute Respiratory Distress Syndrome (ARDS). ECMO has been associated with development of lymphocytopenia that is also common in COVID-19. Hyperinflammation may complicate SARS-CoV-2 pneumonia, prompting therapy with steroids and immunomodulatory drugs. We aimed to evaluate the association of therapies such as steroids and Tocilizumab with trajectories of the total leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers in COVID-19-related ARDS, requiring or not VV-ECMO support. The association of the trajectories of the leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers with treatment with steroids (Steroids), Tocilizumab (Tocilizumab), both drugs (Steroids + Tocilizumab), and absence of treatment (No Treatment) were analyzed using mixed effects regression models, where ECMO was considered as a potential effect modifier. One hundred and thirty-nine leukocyte and eighty-one lymphocyte subpopulation counts were obtained from thirty-one patients who required (VV-ECMO, N = 13) or not (no VV-ECMO, N = 18) extracorporeal support. In both groups, treatment with Steroids + Tocilizumab was independently associated with a significant reduction of 46% and 67% in total lymphocytes, 22% and 60% in CD3+, and 61% and 91% in CD19+ (B lymphocytes) compared to those obtained without treatment, respectively. In the no VV-ECMO group, Tocilizumab was associated with a 79% increase in total lymphocytes and with a reduction in procalcitonin compared to no treatment. CD45+, CD3+CD4+ (Th cell), CD3+CD8+, CD4+/CD8+, the NK cell subpopulation, neutrophils, monocytes, and basophils were significantly reduced by Steroids + Tocilizumab without an effect modification by VV-ECMO support. In critically ill COVID-19 patients with ARDS, concomitant therapies with steroids and Tocilizumab, beside mitigating the inflammation and fibrinolysis, could reduce the total leukocyte, lymphocyte, and subpopulation count. Moreover, the effect of Tocilizumab in increasing the total lymphocytes and reducing procalcitonin might be blunted by VV-ECMO.

Keywords: COVID-19; Tocilizumab; acute respiratory distress syndrome; extracorporeal membrane oxygenation; lymphocytes; steroids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total lymphocyte, CD3+, and CD19+ subpopulation counts in the presence or not of steroids and Tocilizumab therapy in COVID-19 patients with ARDS who required or not ECMO support.
Figure 2
Figure 2
Markers of inflammation with or without steroids and Tocilizumab therapy in COVID-19 patients with ARDS who required or not ECMO support.
See this image and copyright information in PMC

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