Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

Carissimo, Guillaume; Xu, Weili; Kwok, Immanuel; Abdad, Mohammad Yazid; Chan, Yi‐Hao; Fong, Siew‐Wai; Puan, Kia Joo; Lee, Cheryl Yi‐Pin; Yeo, Nicholas Kim‐Wah; Amrun, Siti Naqiah; Chee, Rhonda Sin‐Ling; How, Wilson; Chan, Sui Yung; Fan, Eugene Bingwen; Andiappan, Anand Kumar; Lee, Bernett; Rötzschke, Olaf; Young, Barnaby Edward; Leo, Yee‐Sin; Lye, David C.; Rénia, Laurent; Ng, Lai Guan; Larbi, Anis; Ng, Lisa F. P.

doi:10.1101/2020.06.11.147389

Cited by 11 publications

(12 citation statements)

References 56 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD169 is a sialoadhesin involved in pathogen uptake, which is quickly induced in a type I IFN dependent manner on the surface of monocytes upon Epstein–Barr virus (EBV) or human immunodeficiency virus (HIV) infection (Rempel et al , 2008; Farina et al , 2017). Consistent with our findings, CD169 has been reported on circulating monocytes in COVID-19 patients (Bedin et al , 2020; Carissimo et al , 2020), while type I IFNs have been shown to be a hallmark of SARS-CoV-2 infection and an impaired type I IFN response has been linked with severe disease (Hadjadj et al , 2020; Wilk et al , 2020).…”

Section: Discussionsupporting

confidence: 91%

“…We discovered that the myeloid compartment undergoes profound phenotype changes during a SARS-CoV-2 infection with a decrease in the classical monocyte clusters M1, M2 and M3, a depletion of the intermediate and non-classical monocyte clusters M9 and M8, toward a CD169 + activated monocyte phenotype and a surge of low-density neutrophils early in the disease course. The immature phenotype of the neutrophils is in accordance with data in whole blood (Carissimo et al , 2020).…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

A distinct innate immune signature marks progression from mild to severe COVID-19

Chevrier

Zurbuchen

Cervia

et al. 2020

Preprint

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Excessive inflammation has been postulated to be a major factor in the pathogenesis of severe COVID-19 and innate immune mechanisms are likely to be central in the inflammatory response. We used 40-plex mass cytometry and targeted serum proteomics to profile innate immune cell populations from peripheral blood of patients with mild or severe COVID-19 and healthy controls. Sampling at different stages of COVID-19 allowed us to reconstruct a pseudo-temporal trajectory of the innate immune response. Despite the expected patient heterogeneity, we identified consistent changes during the course of the infection. A rapid and early surge of CD169+ monocytes associated with an IFNy+MCP-2+ signature quickly followed symptom onset; at symptom onset, patients with mild and severe COVID-19 had a similar signature, but over the course of the disease, the differences between patients with mild and severe disease increased. Later in the disease course, we observed a more pronounced re-appearance of intermediate/non-classical monocytes and mounting systemic CCL3 and CCL4 levels in patients with severe disease. Our data provide new insights into the dynamic nature of the early inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identifies sustained pathological innate immune responses as a likely key mechanism in severe COVID-19, further supporting investigation of targeted anti-inflammatory interventions in severe COVID-19.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

A distinct innate immune signature marks progression from mild to severe COVID-19

Chevrier

Zurbuchen

Cervia

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The immunological changes associated with severe disease are also known, with increased inflammatory proteins, coagulopathy and changes in myeloid cell populations reported (6,7). In particular, severe COVID-19 is characterised by expansion of immature myeloid populations, with loss of HLA-DR expression by monocytes and loss of CD10 expression on neutrophils (8,9). Panlymphopenia is also prominent, with CD4+ T cells particularly affected (10,11).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of COVID-19 patients shows age-associated T cell changes independent of ongoing ill-health

Townsend

Dyer

Naughton

et al. 2020

Preprint

View full text Add to dashboard Cite

The trajectory of immunological and inflammatory changes following acute COVID-19 infection are unclear. We investigate immunological changes in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms, termed long COVID.We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed and investigated their relationship with convalescent results.We demonstrate persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common but were not associated with immunological changes.Graphical Abstract

show abstract

“…We also noticed that VCAM1 and CTSE genes were minimally expressed by these blood cells (Figure 3 D and E). T-cells count, which is likely due to its differentiation and activation [47]. Based on this fact, we believe that the low count of FasL-associated CD8+ T cells could result from its activation.…”

Section: Fasl Is Predominantly Expressed By Nk Cells and Cd8+ T Cellsmentioning

confidence: 86%

The aging whole blood transcriptome reveals a potential role of FASLG in COVID-19

Chuffa

Souza

Mello

et al. 2020

Preprint

View full text Add to dashboard Cite

The risk for severe illness from COVID-19 increases with age as older patients are at the highest risk. Although it is still unclear whether the virus is blood-transmitted, the viral RNA is detected in serum. Identifying how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacts with specific blood components during aging is expected to guide proper therapies. Considering that all human coronavirus require host cellular molecules to promote infection, we investigated the aging whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins potentially interacting with viral proteins. From a total of 22 DEGs in aged blood, five genes (FASLG, CTSW, CTSE, VCAM1, and BAG3) changed expression during aging. These age-related genes are involved in immune response, inflammation, cell component and cell adhesion, and platelet activation/aggregation. Both males and females older than 50 overexpress FASLG compared with younger adults (20-30 years old), possibly inducing a hyper-inflammatory cascade that activates specific immune cells. Furthermore, the expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 was significantly increased throughout aging in both gender. By exploring publicly available Single-Cell RNA-Sequencing (scRNA-Seq) data on peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed mainly in natural killer (NK) cells and CD8+ (cytotoxic) T lymphocytes whereas BAG3 was expressed in CD4+ T cells, naive T cells, and CD14+ monocytes. The increased expression of FASLG in blood during aging may explain why older patients are more prone to severe acute viral infection complications. These results indicate FASLG as a prognostic candidate and potential therapeutic target for more aggressive clinical manifestation of COVID-19.

show abstract

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

Cited by 11 publications

References 56 publications

A distinct innate immune signature marks progression from mild to severe COVID-19

A distinct innate immune signature marks progression from mild to severe COVID-19

Longitudinal analysis of COVID-19 patients shows age-associated T cell changes independent of ongoing ill-health

The aging whole blood transcriptome reveals a potential role of FASLG in COVID-19

Contact Info

Product

Resources

About