Long SARS-CoV-2 nucleocapsid sequences in blood monocytes collected soon after hospital admission

Pagano, Nathan; Laurent-Rolle, Maudry; Jc, Hsu; Cb, Vogels; Nd, Grubaugh; Manuelidis, Laura

doi:10.1101/2020.12.16.423113

Cited by 6 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One possibility is that ACE2 translocation is an early event during infection, and infected cells quickly migrate to local organs or quickly undergo pyroptosis 14 . A recent preprint study showing that long SARS-CoV-2 nucleocapsid (N) RNA transcripts were identified in PBMCs from 2 of 11 COVID-19 patients as early as 2 to 6 days after hospital admission 40 . Junqueira's study 14 also showed SARS-CoV-2 N proteins were identified in two minor monocyte subsets (intermediate and non-classical) isolated from 12 COVID-19 patients, and ACE2 surface protein levels were significantly increased in monocytes purified from 4 COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes

Subedi

Liu

et al. 2022

Cell Discov

View full text Add to dashboard Cite

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes

Subedi

Liu

et al. 2022

Cell Discov

View full text Add to dashboard Cite

show abstract

“…Notably, there is still controversy amongst the literature about the susceptibility of human PBMCs to SARS-CoV-2 [50,51]. Although SARS-CoV-2 was detected in immune cells of COVID-19 patients [51][52][53], it remains to be determined whether enhanced activation of the eIF2 pathway in Δ382 SARS-CoV-2 infected patients is directly caused by a loss of ORF8's impact on ER quality control or due to secondary peripheral immune responses to the mutant virus infection, mediated by soluble factors.…”

Section: Discussionmentioning

confidence: 99%

Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection

et al. 2021

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host–pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.

show abstract

“…Установлена длительная персистенция вируса в ЖКТ, дыхательных путях, нервной системе, моноцитах, макрофагах [32][33][34][35][36][37][38].…”

Section: этиология и патогенез поражений органов пищеварения при пост...unclassified

Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines

Гриневич

Лазебник

Kravchuk

et al. 2023

jour

View full text Add to dashboard Cite

Summary Post- COVID syndrome refers to the long-term consequences of a new coronavirus infection COVID-19, which includes a set of symptoms that develop or persist after COVID-19. Symptoms of gastrointestinal disorders in post- COVID syndrome, due to chronic infl ammation, the consequences of organ damage, prolonged hospitalization, social isolation, and other causes, can be persistent and require a multidisciplinary approach. The presented clinical practice guidelines consider the main preventive and therapeutic and diagnostic approaches to the management of patients with gastroenterological manifestations of postCOVID syndrome. The Guidelines were approved by the 17th National Congress of Internal Medicine and the 25th Congress of Gastroenterological Scientifi c Society of Russia.

show abstract

Long SARS-CoV-2 nucleocapsid sequences in blood monocytes collected soon after hospital admission

Cited by 6 publications

References 21 publications

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes

Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection

Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines

Contact Info

Product

Resources

About