Immune Changes in Severe COVID-19 Pulmonary Infections

SARS-CoV-2 outbreak causes a spectrum of clinical patterns that varies from asymptomatic infection to mildly symptomatic manifestations and more-severe forms that need intensive care. Until now, the immune response to SARS-CoV-2 virus infection has been poorly reported to help decision for immune modulation therapies. As a consequence, trials have been designed to test both anti-inflammatory molecules as steroids or anti-bodies against IL-6, and others proposing to "boost" immunity with interferon beta based on similar inclusion criteria.

The immune response to infective agents including viruses may have a complex time evolution with early and late phases corresponding to different patterns, oscillating between pro-inflammation and immune-depression. The potential window to improve outcome in COVID-19 by therapeutic intervention aimed at a fine tuning between immune toxicity and immunodepression requires a longitudinal assessment during the course of illness, especially for the patients who develop acute respiratory failure. Immune monitoring of both innate and adaptive immunity would then be essential to appropriately design clinical trials.

The whole blood cells evaluation was recorded according to the time intervals between the onset of symptoms and the sampling after ICU admission. Patients' care was standardized, especially with regard to ventilation, sedation, and antimicrobial treatment.

In this study the investigators prospectively perform a longitudinal study of both innate and adaptive immunity on patients admitted to ICU for an COVID-19 related acute respiratory failure. The data will be analyzed in reference to the onset of initial symptoms and also to the admission in ICU.

The primary end point is the evolution of the characterization of monocytes and their subsets in term of number and expression of HLA-DR. A similar approach is used for lymphocytes and their subtypes with in addition, an ex vivo testing of their capabilities to be stimulated by SARS-CoV-2 viral proteins in term of TNFalpha, INFgamma, and IL1beta production.

The secondary end-point was to test the association with outcomes and other non-specific markers of inflammation as CRP (C reactive protein), PCT (procalcitonin), DDimers and ferritin.