Notably, 159 confirmed cases have been reported in 23 other countries beyond China, including Japan, Thailand, Singapore, South Korea, Australia, the USA, Malaysia, and Germany. Because of the ...seriousness of this outbreak, WHO declared it a public health emergency of international concern on Jan 30, 2020, followed by the USA announcing a public health emergency on Jan 31, 2020. ...it is important to understand the lung microenvironment and the map of immune responses against 2019-nCoV infection, which might help to define clinical stages and uncover the pathogenesis of the disease. First-line medical staff and scientists in China have had a leading role in fighting the outbreak of 2019-nCoV-associated pneumonia.
There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new ...therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize‐winning hypothesis of the ‘forbidden clone’. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12–67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade.
Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission ...is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.
An outbreak of coronavirus disease 2019 (COVID-19)
, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, has spread globally. Countermeasures are needed to treat and prevent ...further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not ...fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4
effector-GNLY (granulysin), CD8
effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.
LINKED CONTENT
This article is linked to Wu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17667 and https://doi.org/10.1111/apt.17843
We introduce The Benchmark of Linguistic Minimal Pairs (BLiMP),
a challenge set for evaluating the linguistic knowledge of language models (LMs) on major grammatical phenomena in English. BLiMP ...consists of 67 individual datasets, each containing 1,000 minimal pairs—that is, pairs of minimally different sentences that contrast in grammatical acceptability and isolate specific phenomenon in syntax, morphology, or semantics. We generate the data according to linguist-crafted grammar templates, and human aggregate agreement with the labels is 96.4%. We evaluate
-gram, LSTM, and Transformer (GPT-2 and Transformer-XL) LMs by observing whether they assign a higher probability to the acceptable sentence in each minimal pair. We find that state-of-the-art models identify morphological contrasts related to agreement reliably, but they struggle with some subtle semantic and syntactic phenomena, such as negative polarity items and extraction islands.
The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to ...analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.
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•Quantitative lipidomic and metabolomic profiling of COVID-19 plasma•Plasma metabolite panel distinguished COVID-19 from healthy controls (AUC = 0.975)•Differential correlation analyses uncovered metabolic dysregulation in COVID-19•GM3-enriched exosomes are positively correlated with COVID-19 pathogenesis
Plasma metabolite panel effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma monosialodihexosyl gangliosides (GM3s) were negatively correlated with CD4+ T cell count in COVID-19 patients, and GM3-enriched exosomes were positively correlated with disease severity. These observations suggest that GM3-enriched exosomes may participate in pathological processes associated with COVID-19 progression.
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