Transient Lymphopenia and Interstitial Pneumonia With Endotheliitis in SARS-CoV-2–Infected Macaques

Koo, Bon‐Sang; Oh, Hanseul; Kim, Green; Hwang, Eunha; Jung, Hoyin; Lee, Youngjeon; Kang, Philyong; Park, Jae‐Hak; Ryu, Choong-Min; Hong, Jung Joo

doi:10.1093/infdis/jiaa486

Cited by 33 publications

(51 citation statements)

References 13 publications

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“… 1 , 2 Studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a primate model, Koo et al showed that the development of COVID-19 caused acute interstitial pneumonia with endotheliitis in the lungs. 3 These findings strengthen the implications of EC dysfunction in COVID-19. Herein, we provide a review of endothelial receptors that induce or modulate EC dysfunction in COVID-19.…”

mentioning

confidence: 54%

Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19)

Zhang

Tecson

McCullough

2021

Baylor University Medical Center Proceedings

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Endothelial cell (EC) dysfunction contributes to COVID-19–associated vascular inflammation and coagulopathy, and the angiotensin-converting enzyme 2 (ACE2) receptor plays a role in EC dysfunction in COVID-19. To expand the understanding of the role of the ACE2 receptor relative to EC dysfunction, this review addresses (1) tissue distribution of the ACE2 protein and its mRNA expression in humans, (2) susceptibility of the capillary ECs to SARS-CoV-2 infection, and (3) the role of EC dysfunction relevant to ACE2 and nuclear factor-κB in COVID-19.

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mentioning

confidence: 54%

Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19)

Zhang

Tecson

McCullough

2021

Baylor University Medical Center Proceedings

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“…Accordingly, macaques were challenged by multiple routes with a total dose of 2.6 × 10 7 50% tissue culture infectious doses (TCID 50 ), at 10 weeks after the last vaccination. This challenge route and dose were determined based on a model development study in which we challenged macaques that had no previous exposure to the virus [ 30 ]. Two of the three naive macaques showed elevated body temperature after viral infection, while none of the GX-19-vaccinated animals exhibited such symptoms.…”

Section: Resultsmentioning

confidence: 99%

Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Seo¹,

Suh

Ryu³

et al. 2021

Vaccines

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The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

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“…However, these data also point to potential mechanisms of disease in adults. Several studies suggest that severe COVID-19 in adults is, in part, a vascular disease [129][130][131][132] , and a MIS-C like presentation has also been observed in adults 33,133 . Although the age of patients with MIS-C (median of 8 years 40 ) likely provides a clue to MIS-C pathogenesis, it is possible that similar mechanisms of disease can occur across the age spectrum.…”

Section: Discussionmentioning

confidence: 99%

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

Vella

Giles

Baxter

et al. 2020

Preprint

111

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Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8 T cells that correlated with use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct and implicate CD8 T cells in clinical presentation and trajectory of MIS-C.

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Transient Lymphopenia and Interstitial Pneumonia With Endotheliitis in SARS-CoV-2–Infected Macaques

Cited by 33 publications

References 13 publications

Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19)

Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19)

Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

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