This case series uses patient hospital data to summarize the clinical presentation and laboratory and imaging findings of 13 patients with confirmed 2019-nCoV infection admitted to hospitals in ...Beijing in January 2020.
Abstract
Background
The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based ...technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.
Methods
The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort.
Results
The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%).
Conclusions
The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.
The time kinetics of humoral responses against the novel coronavirus (SARS-CoV-2) are characterized in patients with COVID-19 by nucleocapsid-based enzyme-linked immunosorbent assay. The antibody testing can aid in the diagnosis of COVID-19 when combined with quantitative polymerase chain reaction, including in subclinical cases.
Chitin, a potential allergy-promoting pathogen-associated molecular pattern (PAMP), is a linear polymer composed of
N
-acetylglucosamine residues which are linked by
β
-(1,4)-glycosidic bonds. ...Mammalians are potential hosts for chitin-containing protozoa, fungi, arthropods, and nematodes; however, mammalians themselves do not synthetize chitin and thus it is considered as a potential target for recognition by mammalian immune system. Chitin is sensed primarily in the lungs or gut where it activates a variety of innate (eosinophils, macrophages) and adaptive immune cells (IL-4/IL-13 expressing T helper type-2 lymphocytes). Chitin induces cytokine production, leukocyte recruitment, and alternative macrophage activation. Intranasal or intraperitoneal administration of chitin (varying in size, degree of acetylation and purity) to mice has been applied as a routine approach to investigate chitin’s priming effects on innate and adaptive immunity. Structural chitin present in microorganisms is actively degraded by host true chitinases, including acidic mammalian chitinases and chitotriosidase into smaller fragments that can be sensed by mammalian receptors such as FIBCD1, NKR-P1, and RegIIIc. Immune recognition of chitin also involves pattern recognition receptors, mainly via TLR-2 and Dectin-1, to activate immune cells to induce cytokine production and creation of an immune network that results in inflammatory and allergic responses. In this review, we will focus on various immunological aspects of the interaction between chitin and host immune system such as sensing, interactions with immune cells, chitinases as chitin degrading enzymes, and immunologic applications of chitin.
Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local ...microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.
The COVID-19 pandemic has affected more than 20 million people worldwide, with mortality exceeding 800,000 patients. Risk factors associated with severe disease and mortality include advanced age, ...hypertension, diabetes, and obesity. Each of these risk factors pathologically disrupts the lipidome, including immunomodulatory eicosanoid and docosanoid lipid mediators (LMs). We hypothesized that dysregulation of LMs may be a defining feature of the severity of COVID-19. By examining LMs and polyunsaturated fatty acid precursor lipids in serum from hospitalized COVID-19 patients, we demonstrate that moderate and severe disease are separated by specific differences in abundance of immune-regulatory and proinflammatory LMs. This difference in LM balance corresponded with decreased LM products of ALOX12 and COX2 and an increase LMs products of ALOX5 and cytochrome p450. Given the important immune-regulatory role of LMs, these data provide mechanistic insight into an immuno-lipidomic imbalance in severe COVID-19.
An unprecedented global pandemic caused by a novel coronavirus named SARS-CoV-2 has created a severe healthcare threat and become one of the biggest challenges to human health and the global economy. ...As of July 2023, over 767 million confirmed cases of COVID-19 have been diagnosed, including more than 6.95 million deaths. The S protein of this novel coronavirus binds to the ACE2 receptor to enter the host cells with the help of another transmembrane protease TMPRSS2. Infected subjects that can mount an appropriate host immune response can quickly inhibit the spread of infection into the lower respiratory system and the disease may remain asymptomatic or a mild infection. The inability to mount a strong initial response can allow the virus to replicate unchecked and manifest as severe acute pneumonia or prolonged disease that may manifest as systemic disease manifested as viremia, excessive inflammation, multiple organ failure, and secondary bacterial infection among others, leading to delayed recovery, hospitalization, and even life-threatening consequences. The clinical management should be targeted to specific pathogenic mechanisms present at the specific phase of the disease. Here we summarize distinct phases of COVID-19 pathogenesis and appropriate therapeutic paradigms associated with the specific phase of COVID-19.
Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic ...tools. In spite of the development of several assays till date; no single test has proved to be adequate for ATB diagnosis. In this study, we for the first time report the detection of circulating cell-free Mycobacterium tuberculosis (M. tuberculosis) DNA (cfMTB-DNA) in ascitic fluid (AF) samples and its utility in ATB diagnosis. Sixty-five AF samples were included in the study and processed for liquid culture, cytological, biochemical and molecular assays. A composite reference standard (CRS) was formulated to categorize the patients into 'Definite ATB' (M. tuberculosis culture positive, n = 2), 'Probable ATB' (n = 16), 'Possible ATB' (n = 13) and 'Non-TB' category (n = 34). Two molecular assays were performed, namely, the novel cfMTB-DNA qPCR assay targeting M. tuberculosis devR gene and Xpert MTB/RIF assay (Xpert), and their diagnostic accuracy was assessed using CRS as reference standard. Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p0.05). cfMTB-DNA qPCR had a sensitivity of 66.7% (95% CI:40.9,86.7) with 97.1% specificity (95% CI:84.7,99.9) in Definite ATB and Probable ATB group collectively. The sensitivity increased to 70.9% (95% CI:51.9,85.8) in the combined Definite, Probable and Possible ATB group with similar specificity. The cfMTB-DNA qPCR assay performed significantly better than the Xpert assay which demonstrated a poor sensitivity of less than or equal to16.7% with 100% (95% CI:89.7,100) specificity (p0.001). We conclude that cfMTB-DNA qPCR assay is an accurate molecular test that can provide direct evidence of M. tuberculosis etiology and has promise to pave the way for improving ATB diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cytokines are signaling molecules that play a role in myriad processes, including those occurring during diseases and homeostasis. Their homeostatic function begins during embryogenesis and persists ...throughout life, including appropriate signaling for the cell and organism death. During viral infections, antiviral cytokines such as interferons and inflammatory cytokines are upregulated. Despite the well-known benefits of these cytokines, their levels often correlate with disease severity, linking them to unfavorable outcomes. In this review, we discuss both the beneficial and pathological functions of cytokines and the potential challenges in separating these two roles. Further, we discuss challenges in targeting these cytokines during disease and propose a new method for quantifying the cytokine effect to limit the pathological consequences while preserving their beneficial effects.
Summary Background Understanding the amount of tuberculosis managed by the private sector in India is crucial to understanding the true burden of the disease in the country, and thus globally. In the ...absence of quality surveillance data on privately treated patients, commercial drug sales data offer an empirical foundation for disease burden estimation. Methods We used a large, nationally representative commercial dataset on sales of 189 anti-tuberculosis products available in India to calculate the amount of anti-tuberculosis treatment in the private sector in 2013–14. We corrected estimates using validation studies that audited prescriptions against tuberculosis diagnosis, and estimated uncertainty using Monte Carlo simulation. To address implications for numbers of patients with tuberculosis, we explored varying assumptions for average duration of tuberculosis treatment and accuracy of private diagnosis. Findings There were 17·793 million patient-months (95% credible interval 16·709 million to 19·841 million) of anti-tuberculosis treatment in the private sector in 2014, twice as many as the public sector. If 40–60% of private-sector tuberculosis diagnoses are correct, and if private-sector tuberculosis treatment lasts on average 2–6 months, this implies that 1·19–5·34 million tuberculosis cases were treated in the private sector in 2014 alone. The midpoint of these ranges yields an estimate of 2·2 million cases, two to three times higher than currently assumed. Interpretation India's private sector is treating an enormous number of patients for tuberculosis, appreciably higher than has been previously recognised. Accordingly, there is a re-doubled need to address this burden and to strengthen surveillance. Tuberculosis burden estimates in India and worldwide require revision. Funding Bill & Melinda Gates Foundation.
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