COVID-19 causes severity-dependant-alterations of the myeloid cell compartment

« This work is the result of an article rewriting exercise as part of a methodological project. The original article, entitled « Severe COVID-19 is marked by a dysregulated myeloid cell compartment », was published in Cell in September 2020 by Schulte-Schrepping et al..

Symptoms and severity of COVID-19 vary greatly from one individual to another. While some patients experience severe forms characterized by respiratory difficulties, others are asymptomatic or have mild symptoms. The immune response mechanisms of patients with COVID-19 need to be studied in depth.

The hypothesis guiding this work is that the different clinical trajectories of COVID-19 are related to different innate immune responses.

We analyzed blood samples from patients with severe or mild COVID-19 and control patients using high-resolution techniques which allow carrying out analysis at the cell level. Single-cell transcriptomics enables the study of gene expression while single-cell proteomics is about proteins expression. Our study showed that COVID-19 is marked by severity-dependant alterations of the myeloid cell compartment. Moreover, 𝐻𝐿𝐴 − 𝐷𝑅h𝑖𝐶𝐷11𝑐h𝑖 inflammatory monocytes predominate in mild COVID-19 patients whereas 𝐻𝐿𝐴 − 𝐷𝑅𝑙𝑜𝐶𝐷11𝑐𝑙𝑜𝐶𝐷226+𝐶𝐷69+ monocytes predominate in severe COVID-19 patients. Finally, we observed that severe COVID-19 is marked by the release of immature neutrophils with phenotypic signs of immuno- suppression and dysfunction.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of viral zoonosis type, caused by the coronavirus SARS-CoV- 2. This disease, responsible for respiratory tract infection, causes in most cases mild to moderate symptoms. However, for 10 to 20 percent of patients, it degenerates to severe disease, pneumonia, and respiratory failure (Huang et al. 2020b; Wang et al. 2020; Zhou et al. 2020). The fact that this clinical deterioration occurs in the second week of illness suggests that the secondary immune responses are related to the development of severe COVID-19 (Ong et al. 2020).

Numerous studies have been conducted to determine the mechanisms leading to the development of severe COVID-19. The various researchers who have investigated the issue have highlighted a wide variety of clinical responses to COVID-19 and the complexity of the immune responses to the virus. However, complete information on the immunopathology of patients with severe COVID-19 is still lacking. Assuming that the different trajectories of patients are related to distinct responses, particularly within the innate immune system (Chua et al. 2020; Kuri-Cervantes et al. 2020; Mathew et al. 2020; McKechnie and Blish 2020), these findings highlight the importance of detailed analyses of immune responses.

In this paper, we studied the immune responses of individuals in a cohort of COVID-19 patients using single-cell transcriptomics and single-cell proteomics methods.

In COVID-19 patients, severity-dependant-alterations of the myeloid cell compartment were observed. Patients with mild COVID-19 as well as patients with SARS-CoV-2 negative flu-like illness (« FLI ») show increased activations of 𝐻𝐿𝐴 − 𝐷𝑅h𝑖𝐶𝐷11𝑐h𝑖𝐶𝐷14+ monocytes whereas patients with severe COVID-19 have monocytes characterized by low HLA- DR expression and marker genes indicative of anti-inflammatory functions (e.g., CD163 and PLAC8). Finally, the emergency myelopoiesis made appear neutrophil precursors which are dysfunctional neutrophils expressing PD-L1 and exhibiting an impaired oxidative burst response. This appearance in severe COVID-19 patients altered their granulocyte compartments. This study highlights the link between severe COVID-19 and highly dysregulated myeloid cell responses. »