Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors

Cheong, Jin-Gyu; Sharma, Siddhartha; Parkhurst, Christopher N.; Nehar-Belaid, Djamel; Ma, Sai; Paddock, Lucinda; Fatou, Benoit; Karakaslar, Emin Onur; Thibodeau, Asa; Bale, Michael J.; Kartha, Vinay K.; Yee, Jim; Mays, Minh Yen; Leyre, Louise; Paz, Alexia Martínez de; Daman, Andrew W; Alvarez-Mulett, Sergio; Robbins, Lexi; LaFond, Elyse; Weidman, Karissa; Racine‐Brzostek, Sabrina; Yang, He; Price, David H.; Jones, Rebecca; Schenck, Edward J.; Kaner, R.J.; Chadburn, Amy; Zhao, Zhen; Steen, Hanno; Pascual, Virginia; Buenrostro, Jason D.; Niec, Rachel; Lief, Lindsay; Ucar, Duygu; Ravishankar, Arjun

doi:10.1101/2022.02.09.479588

Cited by 21 publications

(37 citation statements)

References 114 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, we identified marked alterations to the expression of surface markers across myeloid cell types following COVID-19, which could play a part in the resulting immune suppression. The long-term changes to the surface expression of these proteins on monocytes and DC may be due to ongoing inflammation or epigenetic changes resulting from severe COVID-19 ( 77 ), possibly altering progenitors in the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

et al. 2023

View full text Add to dashboard Cite

IntroductionAfter more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.MethodsHere, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.ResultsWe found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.ConclusionBy exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

show abstract

Section: Discussionmentioning

confidence: 99%

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

et al. 2023

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…Overall, we identified marked alterations to the expression of surface markers across myeloid cell types following COVID-19. The long-term changes to the surface expression of these proteins on monocytes and DC may be due to epigenetic changes resulting from severe COVID-19 79 , possibly altering progenitors in the bone marrow. COVID-19 severity has been linked to an array of clinical parameters such as the level of soluble urokinase plasminogen activator receptor (suPAR), CRP, and viral load [80][81][82][83] .…”

Section: Discussionmentioning

confidence: 99%

Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19

Hopkins

Govender

Svanberg

et al. 2022

Preprint

View full text Add to dashboard Cite

After more than two years the COVID-19 pandemic continues to burden healthcare systems and economies worldwide, and it is evident that long-term effects of the disease can persist for months post-recovery in some individuals. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to SARS CoV-2 is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed, for 6-7 months, a cohort of COVID-19 patients hospitalized during the early waves of the pandemic. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in PD-L1 expression but increased CD86 expression across almost all cell types examined. Finally, viral load and CRP correlated to the appearance of circulating antibodies and levels of circulating DC and monocyte subsets, respectively. By elucidating some of the long-term effects that SARS-CoV-2 infection has on these key innate myeloid cells, we have shed more light on how the immune landscape remains affected in the months following severe COVID-19.

show abstract

“…Four to 12 months after COVID-19 infection, single-cell transcriptomic and epigenomic analysis of the peripheral blood mononuclear cells enriched in CD34 + HSPCs of affected individuals revealed that that progenitor cells retain their granulopoiesis bias. 141 Specifically, HSPCs from COVID-19-recovered patients demonstrate higher expression of S100A8/A9 and CSF3R and increased chromatin accessibility of these loci. Moreover, mature monocytes retain the altered chromatin accessibility found in progenitor cells and present an increased Type I IFN signature.…”

Section: Neutrophil S and G R Anulop Oie S Is In Tr Ained Innate Immu...mentioning

confidence: 95%

The role of neutrophils in trained immunity

Kalafati

Hatzioannou

Hajishengallis

et al. 2022

Immunological Reviews

View full text Add to dashboard Cite

Summary The principle of trained immunity represents innate immune memory due to sustained, mainly epigenetic, changes triggered by endogenous or exogenous stimuli in bone marrow (BM) progenitors (central trained immunity) and their innate immune cell progeny, thereby triggering elevated responsiveness against secondary stimuli. BM progenitors can respond to microbial and sterile signals, thereby possibly acquiring trained immunity‐mediated long‐lasting alterations that may shape the fate and function of their progeny, for example, neutrophils. Neutrophils, the most abundant innate immune cell population, are produced in the BM from committed progenitor cells in a process designated granulopoiesis. Neutrophils are the first responders against infectious or inflammatory challenges and have versatile functions in immunity. Together with other innate immune cells, neutrophils are effectors of peripheral trained immunity. However, given the short lifetime of neutrophils, their ability to acquire immunological memory may lie in the central training of their BM progenitors resulting in generation of reprogrammed, that is, “trained”, neutrophils. Although trained immunity may have beneficial effects in infection or cancer, it may also mediate detrimental outcomes in chronic inflammation. Here, we review the emerging research area of trained immunity with a particular emphasis on the role of neutrophils and granulopoiesis.

show abstract

Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors

Cited by 21 publications

References 114 publications

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19

The role of neutrophils in trained immunity

Contact Info

Product

Resources

About