Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19 DOI Creative Commons
Michael J. Peluso,

Dylan Ryder,

Robert R. Flavell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

ABSTRACT The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in cohort 24 participants at time points ranging from 27 to 910 days acute using novel radiopharmaceutical agent, [ 18 F]F-AraG, highly selective tracer allows for anatomical quantitation activated T lymphocytes. Tracer uptake the COVID group, which included those with without Long symptoms, was significantly higher compared pre-pandemic controls many regions, including brain stem, spinal cord, bone marrow, nasopharyngeal hilar lymphoid tissue, cardiopulmonary tissues, gut wall. Although cell activation tended be imaged closer illness, increased up 2.5 years infection. observed cord wall associated presence symptoms. In addition, lung tissue persistent pulmonary Notably, these tissues also individuals COVID. Given high F]F-AraG detected gut, we obtained colorectal situ hybridization RNA immunohistochemical studies subset identified cellular rectosigmoid lamina propria all participants, 158 676 initial COVID-19 suggesting could long-term immunological perturbations.

Language: Английский

Distinguishing features of long COVID identified through immune profiling DOI Creative Commons
Jon Klein, Jamie Wood, Jillian R. Jaycox

et al.

Nature, Journal Year: 2023, Volume and Issue: 623(7985), P. 139 - 148

Published: Sept. 25, 2023

Abstract Post-acute infection syndromes may develop after acute viral disease 1 . Infection with SARS-CoV-2 can result in the development of a post-acute syndrome known as long COVID. Individuals COVID frequently report unremitting fatigue, post-exertional malaise, and variety cognitive autonomic dysfunctions 2–4 However, biological processes that are associated persistence these symptoms unclear. Here 275 individuals or without were enrolled cross-sectional study included multidimensional immune phenotyping unbiased machine learning methods to identify features Marked differences noted circulating myeloid lymphocyte populations relative matched controls, well evidence exaggerated humoral responses directed against among participants Furthermore, higher antibody non-SARS-CoV-2 pathogens observed COVID, particularly Epstein–Barr virus. Levels soluble mediators hormones varied groups, cortisol levels being lower Integration data into models identified key most strongly status. Collectively, findings help guide future studies pathobiology developing relevant biomarkers.

Language: Английский

Citations

444
The immunology of long COVID DOI Open Access
Daniel M. Altmann, Emily M. Whettlock, Siyi Liu

et al.

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 618 - 634

Published: July 11, 2023

Language: Английский

Citations

265
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC) DOI Open Access
Amy D. Proal, Michael B. VanElzakker, Soo Aleman

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1616 - 1627

Published: Sept. 4, 2023

Language: Английский

Citations

183
ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature DOI Creative Commons
Anthony L. Komaroff, W. Ian Lipkin

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: June 2, 2023

Some patients remain unwell for months after "recovering" from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance other symptoms that greatly interfere with their ability to function can leave some people housebound disabled. The illness (Long COVID) is similar myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well persisting illnesses follow a wide variety of infectious agents following major traumatic injury. Together, these are projected cost the U.S. trillions dollars. In this review, we first compare ME/CFS Long COVID, noting considerable similarities few differences. We then in extensive detail underlying pathophysiology two conditions, focusing on abnormalities central autonomic nervous system, lungs, heart, vasculature, immune gut microbiome, energy metabolism redox balance. This comparison highlights how strong evidence each abnormality, illness, helps set priorities future investigation. review provides current road map literature biology both illnesses.

Language: Английский

Citations

180
Long COVID: pathophysiological factors and abnormalities of coagulation DOI Creative Commons
Simone Turner, Asad Khan, David Putrino

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(6), P. 321 - 344

Published: April 19, 2023

Acute COVID-19 infection is followed by prolonged symptoms in approximately one ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host (chronic inflammation, metabolic endocrine dysregulation, immune autoimmunity); downstream impacts (tissue damage from the initial infection, tissue hypoxia, dysbiosis, autonomic nervous system dysfunction). These mechanisms culminate long-term persistence disorder characterized a thrombotic endothelialitis, endothelial hyperactivated platelets, fibrinaloid microclots. abnormalities blood vessels coagulation affect every organ represent unifying pathway for various

Language: Английский

Citations

148
Vaccines and therapeutics for immunocompromised patients with COVID-19 DOI Creative Commons
Shmuel Shoham, Carolina Batista, Yanis Ben Amor

et al.

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 59, P. 101965 - 101965

Published: April 12, 2023

Language: Английский

Citations

88
Why we need a deeper understanding of the pathophysiology of long COVID DOI
Akiko Iwasaki, David Putrino

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(4), P. 393 - 395

Published: Feb. 15, 2023

Language: Английский

Citations

87
Long COVID: a review and proposed visualization of the complexity of long COVID DOI Creative Commons
Rubeshan Perumal, Letitia Shunmugam, Kogieleum Naidoo

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 20, 2023

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose visual description the complexity COVID its pathogenesis that can be used by researchers, clinicians, public health officials to guide global effort toward an improved understanding eventual mechanism-based provision care afflicted patients. The proposed visualization framework for should evidence-based, dynamic, modular, systems-level approach condition. Furthermore, further research such could establish strength relationships between pre-existing conditions (or risk factors), biological mechanisms, resulting clinical phenotypes outcomes COVID. Notwithstanding significant contribution disparities in access social determinants have on disease course long our model focuses primarily mechanisms. Accordingly, sets out scientific, clinical, efforts better understand abrogate burden imposed

Language: Английский

Citations

63
Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative DOI Creative Commons
Hector Bonilla, Michael J. Peluso,

Kathleen E. Rodgers

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 9, 2023

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer Post-Acute Sequelae of (PASC), including the unexplained symptoms that are frequently referred as long COVID, which could last for weeks, months, or even years after phase illness. The National Institutes Health is currently funding large multi-center research programs part its Researching COVID Enhance Recover (RECOVER) initiative understand why some do not fully COVID-19. Several ongoing pathobiology studies have provided clues potential mechanisms contributing this condition. These include persistence antigen and/or genetic material, immune dysregulation, reactivation other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. our understanding causes remains incomplete, these early pathophysiologic suggest biological pathways be targeted in therapeutic trials aim ameliorate symptoms. Repurposed medicines novel therapeutics deserve formal testing clinical trial settings prior adoption. While we endorse trials, especially those prioritize inclusion diverse populations affected by COVID-19 discourage off-label experimentation uncontrolled unsupervised settings. Here, review ongoing, planned, future interventions based on current pathobiological processes underlying We focus clinical, pharmacological, feasibility data, with goal informing interventional studies.

Language: Английский

Citations

60
Thromboinflammation in long COVID—the elusive key to postinfection sequelae? DOI Creative Commons
Leo Nicolai, Rainer Kaiser, Konstantin Stark

et al.

Journal of Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 21(8), P. 2020 - 2031

Published: May 11, 2023

Language: Английский

Citations

52