Systems-level immunomonitoring from acute to recovery phase of severe COVID-19

Abstract

The immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNg-Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

“…2G), in keeping with elevated eosinophils in SARS-CoV-2 infected patients during the recovery phase. Their role remains unclear 17 .…”

Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy

“…CD147 has been proposed in pre-prints as both a binding partner for SARS-CoV-2 spike protein and a potential mechanism of cellular entry, although evidence is needed to support this controversial hypothesis (Shilts and Wright, 2020). In the study of Dataset 2, the authors noted that immune responses were dominated by cells expressing CD38 and CD147 (Rodriguez et al, 2020). In the T-REX analysis of the same Dataset 2, for the cells that were changing greatly, CD147 was sometimes present on cells from day 0 that decreased greatly and was lower or absent on cells that emerged only at later times ( Figure 6).…”

“…Also observed were T cell subsets with enrichment of CD38, PD-1, and CD95, as has also been previously reported. While disease severity is not available for individual patients from Dataset 2, it is known that all these cases were at least moderate or severe (Rodriguez et al, 2020). It will be of interest to test the hypothesis that the more severe cases will be one of the two groups, either the patients with very little change and just expansion of cells or those with more major change and a general decrease of cells ( Figure 6).…”

“…To test T-REX on other disease settings, the algorithm was applied to Dataset 2, a mass cytometry study of longitudinal collection of blood from patients with COVID-19 (Rodriguez et al, 2020).…”

“…In contrast, novel respiratory viruses, such as SARS-CoV-2, the coronavirus causing COVID-19, continue to emerge that enact high morbidity and mortality, even among healthy subjects. Understanding the immune response to such viruses is vital to treatment and vaccine design, and there has been rapid progress applying human immune monitoring to COVID-19 patients (Mathew et al, 2020a;Mathew et al, 2020b;Rodriguez et al, 2020). An ongoing challenge in the field is to quantitatively compare novel diseases, like COVID-19, to other disease states and immune responses.…”