The purpose of this study is to analyze in depth the relationship of myeloid cell subpopulations during infection by Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), the virus mediating Covid-19. Myeloid cells include neutrophils, monocytes and dendritic cells, each divided into subpopulations with different functions in immune defense and immune pathologies. The study is based on the following hypotheses: - Infection and the interferon response to infection may induce hyperactive or immunosuppressive differentiation of myeloid cells, that may be treated by specific inhibitors. - Some myeloid cell subpopulations currently identified in our laboratories might be markers for Covid-19 prognosis. - Alternative receptors may be present on myeloid cells, inducing the cytokine storm, a target for therapy. - The expression of Interferon (IFN) receptor and IFN responding genes on myeloid cells and on respiratory epithelial cells may correlate with prognosis and indicate potential treatment targets. - Interferon responses are known to be skewed during Covid-19, but some IFN subtype polymorphisms may correlate with prognosis and these subtypes migt be supplemented or inhibited for therapy.
Infection by SARS-Cov2 drives to pneumonia in most cases, 30 percent of which require
hospitalization in a pneumology ward, among which 30 percent with severe acute respiratory
syndrome (SARS) must go to critical care units, with a high mortality rate.
This infection drives a strong cytokine response. In patients developing SARS, a profound,
paradoxical defect in IFN alpha and in the expression of genes responding to IFN alpha was
discovered. IFNs are strong anti-viral proteins, used for the treatment of viral hepatitis.
Type I IFNs, including IFN alpha, have ubiquitous receptors on almost every cell type. Type
III IFNs, or IFN lambda, have a more restricted receptor expression, including on
neutrophils. Their polymorphisms were already related to the prognosis of another ribonucleic
acid (RNA) virus with mucosal entry, hepatitis C virus (HCV), especially in people with
African origins.
Coronaviruses responsible for the previous SARS-Cov or Middle East respiratory syndrome
coronavirus (MERS-Cov) epidemics induce a defective IFN signal transduction. Many other viral
infection lead to desensitization. Moreover, IFN alpha by itself can lead to defective
antiviral responses. At the immune cell level, lymphopenia with an increased
neutrophil/lymphocyte ratio were noted in severe SARS-Cov2 case. New subpopulations of
neutrophils have been characterized by phenotypic and proteomic studies, with inflammatory or
suppressive functions.
It will be important to know if
- hyperactive or immunosuppressive myeloid cell differentiation is caused by SARS-Cov2 and
can be inhibited specifically.
- some myeloid subpopulations
- correlate with the prognosis of the disease,
- myeloid cells have alternative receptors for SARS-Cov2,
- some IFN polymorphisms may correlate with prognosis and might be supplemented or
inhibited for therapy.
The answers will be obtained through the primary and secondary outcome measures, as described
below.
Other: Blood sampling
Peripheral Blood sampling, 25 mL
Other: Nasal Brushing
Nasal Brushing, facultative
Inclusion Criteria:
- Age > 18 years
- Sex : male or female
- French Social Security insurance
- Information and consent dated and signed *
- Group 1 : inclusion 2 to 12 months after hospitalization for Covid-19 pneumonia with
mild severity (oxygen treatment ≤5L/mn);
- Group 2 : 2 to 12 months after hospitalization for Covid-19 pneumonia with high
severity (oxygen treatment >5L/mn);
- Group 3 : external visit at Cochin Hospital, age- and sex -matched with Groups 1, 2,
4.
- Group 4 : inclusion during hospitalization for Covid-19, within the first month of
symptoms.
Exclusion Criteria:
- Tuberculosis or other evolutive bacterial infection
- Chronic evolutive viral Infections (Hepatitis B or C, HIV)
- Ongoing chemotherapy or radiotherapy
- Participation in another research protocol with current exclusion period at the time
of pre-inclusion (possible inclusion in an observational study
- Vulnerable person (pregnant, parturient woman, breastfeeding woman, person Under
tutorship, person under arrest through judiciary or administrative decision )
Pierre-Régis Burgel, MD, PhD
01 58 41 23 49 - +33
pierre-regis.burgel@cch.aphp.fr
Marie BENHAMMANI-Godard
01 58 41 12 11 - +33
marie.godard@aphp.fr
Pierre-Régis Burgel, MD, PhD, Principal Investigator
Cochin Hospital