A consensus Covid-19 immune signature combines immune-protection with discrete sepsis-like traits associated with poor prognosis
Authors:Laing et al.
Link to paper: https://doi.org/10.1101/2020.06.08.20125112
Tags: Diagnostics, Immunology/Immunity
Mild, moderate and severe COVID-19 patients produce anti-SARS-CoV-2 antibodies.
Changes in the proportions of subsets of B, DC, monocytes and T cells in COVID-19s patients similar to those seen in sepsis.
Elevated IP10, decrease basophils and pDC population and chronic T cell activation is correlated with disease severity.
This study shows the first results of the COVID-ImmunoPhenotyping project (COVID-IP,London). Flow cytometry analysis of blood cells using 8 multiparameter panels associated with cytokine and anti-SARS-CoV2 antibody detections by ELISA were performed on a cohort of 63 hospitalized COVID-19 patients and 55 healthy controls the first day of hospitalisation.
As previously reported in other cohorts, most COVID-19 patients had SARS-CoV2 antibody response, elevated cytokines, and pan-lymphopenia. While these factors were not associated with the disease severity, the decrease in basophils and pDC, the downregulation of HLA-DR and CD86 on some monocytes and DC populations and the increased level of IP-10 were. Furthermore, in addition to the overall sepsis-like T cell subsets dysregulation and depletion, some discrete parameters such as the expression of exhaustion markers were also good indicators of the disease severity.
This analysis revealed a particular COVID immune signature that could be adapted, in a prediction purpose, for the early screening of patients.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19 – the results of this study imply prognostic value for immunophenotyping coronavirus patients and identifying those at risk of developing more severe disease e.g. by elevated IP10 plasma levels and T cytopenia accompanied by chronic activation phenotype associated with immune exhaustion.
Clinical Cohort study (63 COVID-19 patients and 55 healthy control)
Strengths and limitations of the paper
Novelty: This study suggests that specific differences in the immune response mounted against SARS-CoV-2 may account in part for differences in disease severity between patients, identifying changes to specific immune cell subsets and a T cell exhaustion phenotype characteristic of more severe disease.
Standing in the field: Similarly to previous publication, they report the presence of anti SARS-CoV2 antibodies in most patients, T cell exhaustion phenotype and cytopenia (also reported in sepsis patients). In contrast to previous studies, they didn’t observe drastic neutrophils and NK cell number modification in their cohort.
Appropriate statistics: Yes, and data adjusted for differences in age and sex of patients
Viral model used:Patients with SARS-CoV-2
Translatability: Potential to apply this blood immunophenotyping on detected COVID-19 patients to generate at early timepoint risk based patient stratification.
Main limitations: Small cohort of 63 patients. Temporal variation in sampling as all patients sampled on day 1 i.e. day of positive qPCR test, not day of symptom onset. Not all patients were then followed up for blood tests at days 3 and 9. The differences they identify between severe and non-severe disease (e.g. T cell exhaustion phenotype, elevated IP10) will not be of prognostic value if they arise after the onset of severe symptoms.