Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Burnett, Cassandra E.; Okholm, Trine Line Hauge; Tenvooren, Iliana; Márquez, Diana M.; Tamaki, Stanley; Sandoval, Priscila Muñoz; Willmore, Andrew; Hendrickson, Carolyn M.; Kangelaris, Kirsten N.; Langelier, Charles; Krummel, Matthew F.; Woodruff, Prescott G.; Calfee, Carolyn S.; Erle, David J.; Ansel, K. Mark; Spitzer, Matthew H.; Patel, Ravi K.; Abe-Jones, Yumiko; Asthana, Saurabh; Beagle, Alexander J.; Bhide, Sharvari; Cai, Chen; Calvo, Maria Lorena Espinar; Carrillo, Sidney; Chak, Suzanna; Collins, Zachary; Darmanis, Spyros; Fragiadakis, Gabriela K.; Ghale, Rajani; Giberson, Jeremy; Glenn, Pat; Gonzalez, Ana; Hiam-Galvez, Kamir J; Jauregui, Alejandra; Ke, Serena; Lea, Tasha; Lee, Deanna; Lota, Raphael; Lupin-Jimenez, Leonard; Nguyễn, Việt Hà; Nigam, Nishita; Pierce, Logan; Prasad, Priya; Rao, Arjun A.; Rashid, Sadeed; Rodriguez, Nicklaus; Samad, Bushra; Shaw, Cole; Sigman, Austin; Sinha, Pratik; Tang, Kevin; Altamirano, Luz Torres; Tumurbaatar, Erden; Upadhyay, Vaibhav; Ward, Alyssa; Wong, Kristine; Ye, Chun Jimmie; Yee, Kimberly; Zhou, Mingyue

doi:10.1016/j.immuni.2022.06.004

Cited by 13 publications

(10 citation statements)

References 34 publications

(34 reference statements)

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“…Similar results were seen in a different study using whole blood and granulocyte samples, wherein the authors found signatures of activated neutrophils and potentially suppressive neutrophil function in severe COVID‐19 patients 67 . Interestingly, in a longitudinal study, it was demonstrated that patients who recovered from COVID‐19, besides having neutrophils that returned to baseline levels of circulating neutrophils, also showed a reduction in PD‐L1 expression on neutrophils by the time of discharge 68 . Whether the overall signature or program of neutrophils returns to that observed during homeostasis following recovery from COVID‐19 is still not entirely known and whether the immunosuppressive phenotype persists in long‐COVID also is unclear.…”

Section: Neutrophil Heterogeneity During Sars‐cov‐2 Infectionsupporting

confidence: 78%

“… 67 Interestingly, in a longitudinal study, it was demonstrated that patients who recovered from COVID‐19, besides having neutrophils that returned to baseline levels of circulating neutrophils, also showed a reduction in PD‐L1 expression on neutrophils by the time of discharge. 68 Whether the overall signature or program of neutrophils returns to that observed during homeostasis following recovery from COVID‐19 is still not entirely known and whether the immunosuppressive phenotype persists in long‐COVID also is unclear. Certainly in bacterial sepsis it is well known that a subset of patients develop a long sepsis phenotype and are much more likely to develop subsequent often unrelated infections suggesting some long‐term impact on neutrophil function.…”

Section: Neutrophil Heterogeneity During Sars‐cov ...mentioning

confidence: 99%

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Neutrophils during SARS‐CoV‐2 infection: Friend or foe?

Castanheira

Kubes

2022

Immunological Reviews

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Summary Coronavirus disease 2019 (COVID‐19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and has resulted in more than 6 million deaths worldwide. COVID‐19 is a respiratory disease characterized by pulmonary dysfunction leading to acute respiratory distress syndrome (ARDs), as well as disseminated coagulation, and multi‐organ dysfunction. Neutrophils and neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of COVID‐19. In this review, we highlight key gaps in knowledge, discuss the heterogeneity of neutrophils during the evolution of the disease, how they can contribute to COVID‐19 pathogenesis, and potential therapeutic strategies that target neutrophil‐mediated inflammatory responses.

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Section: Neutrophil Heterogeneity During Sars‐cov‐2 Infectionsupporting

confidence: 78%

Section: Neutrophil Heterogeneity During Sars‐cov ...mentioning

confidence: 99%

Neutrophils during SARS‐CoV‐2 infection: Friend or foe?

Castanheira

Kubes

2022

Immunological Reviews

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“…After removing duplicates, 268 studies were screened for their eligibility, of which 17 were ultimately included in this review. Three studies (47)(48)(49) were deemed potentially relevant but could not be included due to insufficient characterization of the convalescent cohort in terms of the time point of blood sampling (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – Implications for Long COVID?

Haunhorst

Bloch

Javelle

et al. 2022

Preprint

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Background: Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms. Objective: The aim of this scoping review was to investigate if regulatory T cell (Treg) dysregulation is observable beyond the acute illness and if it might be involved in Long COVID immunopathology. Design: A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science. Results: The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome's etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population. Conclusions: Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.

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“…Recent studies indicated ICs played an important role in fighting COVID-19 [ 43 , 63 ], and monocytes were associated with the risk stratifications and cytokine storms of COVID-19 patients [ 64 , 65 ]. Previous researches showed that circulating monocytes played a role in all stages of SARS-Cov-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics and immune cells’ profiling of COVID-19 patients for ICU admission prediction: in silico analysis and an integrated machine learning-based approach in the framework of Predictive, Preventive, and Personalized Medicine

et al. 2023

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Background Intensive care unit admission (ICUA) triage has been urgent need for solving the shortage of ICU beds, during the coronavirus disease 2019 (COVID-19) surge. In silico analysis and integrated machine learning (ML) approach, based on multi-omics and immune cells (ICs) profiling, might provide solutions for this issue in the framework of predictive, preventive, and personalized medicine (PPPM). Methods Multi-omics was used to screen the synchronous differentially expressed protein-coding genes (SDEpcGs), and an integrated ML approach to develop and validate a nomogram for prediction of ICUA. Finally, the independent risk factor (IRF) with ICs profiling of the ICUA was identified. Results Colony-stimulating factor 1 receptor (CSF1R) and peptidase inhibitor 16 (PI16) were identified as SDEpcGs, and each fold change (FC ij ) of CSF1R and PI16 was selected to develop and validate a nomogram to predict ICUA. The area under curve (AUC) of the nomogram was 0.872 (95% confidence interval (CI): 0.707 to 0.950) on the training set, and 0.822 (95% CI: 0.659 to 0.917) on the testing set. CSF1R was identified as an IRF of ICUA, expressed in and positively correlated with monocytes which had a lower fraction in COVID-19 ICU patients. Conclusion The nomogram and monocytes could provide added value to ICUA prediction and targeted prevention, which are cost-effective platform for personalized medicine of COVID-19 patients. The log 2 fold change (log 2 FC) of the fraction of monocytes could be monitored simply and economically in primary care, and the nomogram offered an accurate prediction for secondary care in the framework of PPPM. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-023-00317-5.

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Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Cited by 13 publications

References 34 publications

Neutrophils during SARS‐CoV‐2 infection: Friend or foe?

Neutrophils during SARS‐CoV‐2 infection: Friend or foe?

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – Implications for Long COVID?

Multi-omics and immune cells’ profiling of COVID-19 patients for ICU admission prediction: in silico analysis and an integrated machine learning-based approach in the framework of Predictive, Preventive, and Personalized Medicine

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