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1.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1787524

ABSTRACT

COVID-19 is spreading widely, and the pandemic is seriously threatening public health throughout the world. A comprehensive study on the optimal sampling types and timing for an efficient SARS-CoV-2 test has not been reported. We collected clinical information and the values of 55 biochemical indices for 237 COVID-19 patients, with 37 matched non-COVID-19 pneumonia patients and 131 healthy people in Inner Mongolia as control. In addition, the results of dynamic detection of SARS-CoV-2 using oropharynx swab, pharynx swab, and feces were collected from 197 COVID-19 patients. SARS-CoV-2 RNA positive in feces specimen was present in approximately one-third of COVID-19 patients. The positive detection rate of SARS-CoV-2 RNA in feces was significantly higher than both in the oropharynx and nasopharynx swab (P < 0.05) in the late period of the disease, which is not the case in the early period of the disease. There were statistically significant differences in the levels of blood LDH, CRP, platelet count, neutrophilic granulocyte count, white blood cell number, and lymphocyte count between COVID-19 and non-COVID-19 pneumonia patients. Finally, we developed and compared five machine-learning models to predict the prognosis of COVID-19 patients based on biochemical indices at disease onset and demographic characteristics. The best model achieved an area under the curve of 0.853 in the 10-fold cross-validation.

2.
Front Microbiol ; 13: 865336, 2022.
Article in English | MEDLINE | ID: covidwho-1775717

ABSTRACT

A reliable and reproducible model in vitro for swine enteric coronaviruses infection would be intestinal models that support virus replication and can be long-term cultured and manipulated experimentally. Here, we designed a robust long-term culture system for porcine intestinal organoids from the intestinal crypt or single LGR5+ stem cell by combining previously defined insights into the growth requirements of the intestinal epithelium of humans. We showed that long-term cultured swine intestinal organoids were expanded in vitro for more than 6 months and maintained the potential to differentiate into different types of cells. These organoids were successfully infected with porcine enteric coronavirus, including porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), and were capable of supporting virus replication and progeny release. RNA-seq analysis showed robust induction of transcripts associated with antiviral signaling in response to enteric coronavirus infection, including hundreds of interferon-stimulated genes and cytokines. Moreover, gene set enrichment analysis indicated that PEDV infection could suppress the immune response in organoids. This 3D intestinal organoid model offers a long-term, renewable resource for investigating porcine intestinal infections with various pathogens.

3.
PLoS One ; 17(2): e0263680, 2022.
Article in English | MEDLINE | ID: covidwho-1714773

ABSTRACT

To date, literature has depicted an increase in mortality among patients with hip fractures, directly related to acute coronavirus disease 2019 (COVID-19) infection and not due to underlying comorbidities. Usual orthogeriatric pathway in our Department was disrupted during the pandemic. This study aimed to evaluate early mortality within 30 days, in 2019 and 2020 in our Level 1 trauma-center. We compared two groups of patients aged >60 years, with osteoporotic upper hip fractures, in February/March/April 2020 and February/March/April 2019, in our level 1 trauma center. A total of 102 and 79 patients met the eligibility criteria in 2019 and 2020, respectively. Mortality was evaluated, merging our database with the French open database for death from the INSEE, which is prospectively updated each month. Causes of death were recorded. Charlson Comorbidity Index was evaluated for comorbidities, Instrumental Activity of Daily Living (IADL), and Activity of Daily Living (ADL) scores were assessed for autonomy. There were no differences in age, sex, fracture type, Charlson Comorbidity Index, IADL, and ADL. 19 patients developed COVID-19 infection. The 30-day survival was 97% (95% CI, 94%-100%) in 2019 and 86% (95% CI, 79%-94%) in 2020 (HR = 5, 95%CI, 1.4-18.2, p = 0.013). In multivariable Cox'PH model, the period (2019/2020) was significantly associated to the 30-day mortality (HR = 6.4, 95%CI, 1.7-23, p = 0.005) and 6-month mortality (HR = 3.4, 95%CI, 1.2-9.2, p = 0.01). COVID infection did not modify significantly the 30-day and 6-month mortality. This series brought new important information, early mortality significantly increased because of underlying disease decompensation. Minimal comprehensive care should be maintained in all circumstances in order to avoid excess of mortality among elderly population with hip fractures.


Subject(s)
COVID-19 , Hip Fractures/mortality , Activities of Daily Living , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pandemics , Survival Rate , Trauma Centers , Virulence
4.
Vaccines (Basel) ; 10(2)2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1708201

ABSTRACT

(1) Background: Although there are extensive data on admission co-variates and outcomes of persons with coronavirus infectious disease-2019 (COVID-19) at diverse geographic sites, there are few, if any, subject-level comparisons between sites in regions and countries. We investigated differences in hospital admission co-variates and outcomes of hospitalized people with COVID-19 between Wuhan City, China and the New York City region, USA. (2) Methods: We retrospectively analyzed clinical data on 1859 hospitalized subjects with COVID-19 in Wuhan City, China, from 20 January to 4 April 2020. Data on 5700 hospitalized subjects with COVID-19 in the New York City region, USA, from 1 March to 4 April 2020 were extracted from an article by Richardson et al. Hospital admission co-variates (epidemiological, demographic, and laboratory co-variates) and outcomes (rate of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], major organ failure and death, and length of hospital stay) were compared between the cohorts. (3) Results: Wuhan subjects were younger, more likely female, less likely to have co-morbidities and fever, more likely to have a blood lymphocyte concentration > 1 × 109/L, and less likely to have abnormal liver and cardiac function tests compared with New York subjects. There were outcomes data on all Wuhan subjects and 2634 New York subjects. Wuhan subjects had higher blood nadir median lymphocyte concentrations and longer hospitalizations, and were less likely to receive IMV, ICU hospitalization, and interventions for kidney failure. Amongst subjects not receiving IMV, those in Wuhan were less likely to die compared with New York subjects. In contrast, risk of death was similar in subjects receiving IMV at both sites. (4) Conclusions: We found different hospital admission co-variates and outcomes between hospitalized persons with COVID-19 between Wuhan City and the New York region, which should be useful developing a comprehensive global understanding of the SARS-CoV-2 pandemic and COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325133

ABSTRACT

In the absence of an effective vaccine or treatment, the current best defence against COVID-19 is social distancing—staying at home as much as possible, keeping distance from others, and avoiding large gatherings. Although social distancing maximizes physical health, we know little about its psychological consequences. In this research (N = 374), we investigated the effect of social distancing duration on negative moods and memory. The relation between social distancing duration and both negative mood and memory errors followed the same U-shaped function: negative moods and memory errors initially decreased steadily as social distancing duration increased, at which point (~ 30 days) they began to steadily increase. Subsequent analyses indicated that memory errors were mediated by lonely mood in particular. Thus, short-term social distancing might benefit psychological well-being and memory performance, but extended social distancing has the expected negative impact on mood and memory.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312650

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has spread to 216 countries and territories around the world. Most studies on response to public health emergencies, focus on health systems, local governments or medical organizations, but fewer studies focus on individuals. However, medical staff are the core strength for responding to public health emergencies. The aims of this study are to investigate the status of medical staff’s emergency capacity during the pandemic and to provide intellectual support to further enhance medical staff's ability to ensure the smooth operation of medical rescue. Methods: : This study conducted a cross-sectional survey of four hospitals designated to treat patients with COVID-19 in China. Based on the emergency capacity system of medical staff for infectious diseases, an improved Emergency Preparedness Information Questionnaire was used to evaluate the emergency capacity of medical staff. Linear regression and one-way analysis of variance were used to test the differences in the emergency capacity of medical staff. Spearman correlation analysis was used to study the correlation between the self-efficacy and emergency capacity of medical staff. Results: : The overall emergency capacity of the surveyed medical staff was at a medium level. There was a correlation between emergency capacity and age, working years, position, educational background and the area where medical staff worked. Emergency capacity was not related to the hospital grade. Emergency capacity was significantly related to whether medical staff had participated in frontline pandemic prevention work. There was also a positive correlation between emergency capacity and the self-efficacy of medical staff. Conclusions: : The results highlight the importance of the training mechanism for emergency personnel. The emergency input for public health emergencies should be increased to improve the emergency capacity of medical staff. In addition, it is necessary to pay attention to the mental health of medical staff.

7.
Cell ; 185(6): 1025-1040.e14, 2022 03 17.
Article in English | MEDLINE | ID: covidwho-1649487

ABSTRACT

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.


Subject(s)
Antibodies, Viral , COVID-19 , Germinal Center , Antigens, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccination
8.
Sci Transl Med ; 14(635): eabm7853, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1630954

ABSTRACT

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19 Vaccines , Humans , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296347

ABSTRACT

There is a continuously growing demand for emergency department (ED) services across the world, especially under the COVID-19 pandemic. Risk triaging plays a crucial role in prioritizing limited medical resources for patients who need them most. Recently the pervasive use of Electronic Health Records (EHR) has generated a large volume of stored data, accompanied by vast opportunities for the development of predictive models which could improve emergency care. However, there is an absence of widely accepted ED benchmarks based on large-scale public EHR, which new researchers could easily access. Success in filling in this gap could enable researchers to start studies on ED more quickly and conveniently without verbose data preprocessing and facilitate comparisons among different studies and methodologies. In this paper, based on the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database, we proposed a public ED benchmark suite and obtained a benchmark dataset containing over 500,000 ED visits episodes from 2011 to 2019. Three ED-based prediction tasks (hospitalization, critical outcomes, and 72-hour ED revisit) were introduced, where various popular methodologies, from machine learning methods to clinical scoring systems, were implemented. The results of their performance were evaluated and compared. Our codes are open-source so that anyone with access to MIMIC-IV-ED could follow the same steps of data processing, build the benchmarks, and reproduce the experiments. This study provided insights, suggestions, as well as protocols for future researchers to process the raw data and quickly build up models for emergency care.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294373

ABSTRACT

Background: Although there are extensive data on admission co-variates and outcomes of persons with coronavirus infectious disease-2019 (COVID-19) at diverse geographic sites there are few if any subject-level comparisons between sites in regions and countries. We aim to comparatively investigate differences in hospital admission co-variates and outcomes of hospitalized people with COVID-19 between Wuhan City, China and the New York City region, USA. Methods We retrospectively collected clinical data on 1859 Hospitalized subjects with COVID-19 in Wuhan City, China 20 January to 4 April, 2020. Data on those 5700 hospitalized subjects with COVID-19 in the New York City region, USA 1 March to 4 April, 2020 was drawn from a published article by Richardson et al . Hospital admission co-variates (epidemiological, demographic and laboratory co-variates) and outcomes (rate of intensive care unit(ICU) admission, invasive mechanical ventilation(IMV), major organ failure and death and length of hospital stay) were compared between the two cohorts. Results Wuhan subjects were younger, more likely female, less likely to have co-morbidities and fever, more likely to have a blood lymphocyte concentration > 1×10E+9/L and less likely to have abnormal liver and cardiac function tests compared with the New York subjects. There were outcomes data on all Wuhan subjects and 2,634 New York subjects. Wuhan subjects had higher blood nadir median lymphocyte concentrations and longer hospitalizations, were less likely to receive IMV, ICU hospitalization and kidney replacement therapy. Amongst subjects not receiving IMV those in Wuhan were less likely to die compared with New York subjects. In contrast, risk of death was similar in subjects receiving IMV at both sites. Conclusions We found different hospital admission co-variates and outcomes between hospitalized persons with COVID-19 between Wuhan City and the New York region, which should be useful developing a comprehensive global understanding of the SARS-CoV-2 pandemic and COVID-19.

11.
Viruses ; 13(10)2021 09 24.
Article in English | MEDLINE | ID: covidwho-1438745

ABSTRACT

SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VEDIS), the ability to block symptomatic COVID-19. They only partially discriminate whether VEDIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VESUSC), or by preventing symptoms despite infection (VESYMP). Vaccine efficacy against transmissibility given infection (VEINF), the decrease in secondary transmissions from infected vaccine recipients, is also not measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna (mRNA-1273QS) and Pfizer-BioNTech (BNT162b2) vaccines, which demonstrated VEDIS > 90% in clinical trials, mediate VEDIS by VESUSC, then a limited fourth epidemic wave of infections with the highly infectious B.1.1.7 variant would have been predicted in spring 2021 assuming rapid vaccine roll out. If high VEDIS is explained by VESYMP, then high VEINF would have also been necessary to limit the extent of this fourth wave. Vaccines which completely protect against infection or secondary transmission also substantially lower the number of people who must be vaccinated before the herd immunity threshold is reached. The limited extent of the fourth wave suggests that the vaccines have either high VESUSC or both high VESYMP and high VEINF against B.1.1.7. Finally, using a separate intra-host mathematical model of viral kinetics, we demonstrate that a 0.6 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve 50% VEINF, which suggests that human challenge studies with a relatively low number of infected participants could be employed to estimate all three vaccine efficacy metrics.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , COVID-19/immunology , COVID-19 Vaccines/pharmacology , Humans , Models, Theoretical , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Vaccines/pharmacology , Washington
12.
J Med Internet Res ; 23(9): e24081, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1403378

ABSTRACT

BACKGROUND: The COVID-19 outbreak has now become a pandemic and has had a serious adverse impact on global public health. The effect of COVID-19 on the lungs can be determined through 2D computed tomography (CT) imaging, which requires a high level of spatial imagination on the part of the medical provider. OBJECTIVE: The purpose of this study is to determine whether viewing a 3D hologram with mixed reality techniques can improve medical professionals' understanding of the pulmonary lesions caused by COVID-19. METHODS: The study involved 60 participants, including 20 radiologists, 20 surgeons, and 20 medical students. Each of the three groups was randomly divided into two groups, either the 2D CT group (n=30; mean age 29 years [range 19-38 years]; males=20) or the 3D holographic group (n=30; mean age 30 years [range 20=38 years]; males=20). The two groups completed the same task, which involved identifying lung lesions caused by COVID-19 for 6 cases using a 2D CT or 3D hologram. Finally, an independent radiology professor rated the participants' performance (out of 100). All participants in two groups completed a Likert scale questionnaire regarding the educational utility and efficiency of 3D holograms. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) was completed by all participants. RESULTS: The mean task score of the 3D hologram group (mean 91.98, SD 2.45) was significantly higher than that of the 2D CT group (mean 74.09, SD 7.59; P<.001). With the help of 3D holograms, surgeons and medical students achieved the same score as radiologists and made obvious progress in identifying pulmonary lesions caused by COVID-19. The Likert scale questionnaire results showed that the 3D hologram group had superior results compared to the 2D CT group (teaching: 2D CT group median 2, IQR 1-2 versus 3D group median 5, IQR 5-5; P<.001; understanding and communicating: 2D CT group median 1, IQR 1-1 versus 3D group median 5, IQR 5-5; P<.001; increasing interest: 2D CT group median 2, IQR 2-2 versus 3D group median 5, IQR 5-5; P<.001; lowering the learning curve: 2D CT group median 2, IQR 1-2 versus 3D group median 4, IQR 4-5; P<.001; spatial awareness: 2D CT group median 2, IQR 1-2 versus 3D group median 5, IQR 5-5; P<.001; learning: 2D CT group median 3, IQR 2-3 versus 3D group median 5, IQR 5-5; P<.001). The 3D group scored significantly lower than the 2D CT group for the "mental," "temporal," "performance," and "frustration" subscales on the NASA-TLX. CONCLUSIONS: A 3D hologram with mixed reality techniques can be used to help medical professionals, especially medical students and newly hired doctors, better identify pulmonary lesions caused by COVID-19. It can be used in medical education to improve spatial awareness, increase interest, improve understandability, and lower the learning curve. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045845; http://www.chictr.org.cn/showprojen.aspx?proj=125761.


Subject(s)
Augmented Reality , COVID-19 , Students, Medical , Adult , Humans , Lung , Male , SARS-CoV-2 , United States , Young Adult
13.
Org Lett ; 23(16): 6278-6282, 2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1397832

ABSTRACT

A visible-light-induced multicomponent reaction of ethyl diazoacetate, diarylamines, and styrene-type alkenes is described. This novel 1,2-difunctionalization of alkenes can be readily achieved under a simple operation and mild conditions, affording γ-amino esters as major products. The reaction proceeds through the generation of carbon-centered radicals from diazo compounds by a visible-light-promoted proton-coupled electron transfer (PCET) process. The carbon radicals then add to diverse alkenes, delivering new carbon radical species, and the final products are formed with N-centered radicals via a radical-radical coupling.

15.
Nature ; 596(7872): 410-416, 2021 08.
Article in English | MEDLINE | ID: covidwho-1305364

ABSTRACT

The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+ inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.


Subject(s)
Adaptive Immunity , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity, Innate , T-Lymphocytes/immunology , Vaccinology , Adult , Aged , Antibodies, Neutralizing/immunology , Autoantibodies/immunology , COVID-19 Vaccines/administration & dosage , Female , Humans , Immunization, Secondary , Male , Middle Aged , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/immunology , Transcription, Genetic , Transcriptome/genetics , Young Adult
16.
Front Cell Infect Microbiol ; 11: 650487, 2021.
Article in English | MEDLINE | ID: covidwho-1167306

ABSTRACT

Background: Convalescent plasma (CP) transfusion is considered to be the priority therapeutic option for COVID-19 inpatients when no specific drugs are available for emerging infections. An alternative, simple, and sensitive method is urgently needed for clinical use to detect neutralization activity of the CP to avoid the use of inconvenient micro-neutralization assay. Method: This study aims to explore optimal index in predicting the COVID-19 CP neutralization activity (neutralizing antibody titers, NAb titers) in an indirect ELISA format. Fifty-seven COVID-19-recovered patients plasma samples were subjected to anti-SARS-CoV-2 RBD, S1, and N protein IgG antibody by indirect ELISA. Results: ELISA-RBD exhibited high specificity (96.2%) and ELISA-N had high sensitivity (100%); while ELISA-S1 had low sensitivity (86.0%) and specificity (73.1%). Furthermore, ELISA-RBD IgG titers and pseudovirus-based NAb titers correlated significantly, with R2 of 0.2564 (P < 0.0001). Conclusion: ELISA-RBD could be a substitute for the neutralization assay in resource-limited situations to screen potential plasma donors for further plasma infusion therapy.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/blood , COVID-19/therapy , Immunization, Passive/methods , Plasma/immunology , Animals , Antibodies, Viral/therapeutic use , Antiviral Agents/therapeutic use , Blood Donors , China , Chlorocebus aethiops , Cohort Studies , Enzyme-Linked Immunosorbent Assay , HEK293 Cells , Humans , Immunoglobulin G/blood , SARS-CoV-2 , Sensitivity and Specificity , Vero Cells
17.
Elife ; 102021 03 23.
Article in English | MEDLINE | ID: covidwho-1146275

ABSTRACT

Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/etiology , Endothelium, Vascular/pathology , Lymphocyte Activation , Adult , Aged , COVID-19/immunology , COVID-19/pathology , Cardiovascular Diseases/immunology , Cardiovascular Diseases/pathology , Cytokines/immunology , Endothelial Cells/immunology , Endothelial Cells/pathology , Endothelium, Vascular/immunology , Female , Humans , Male , Middle Aged , Risk Factors
18.
Clinical and Experimental Pharmacology and Physiology ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1077199

ABSTRACT

Abstract Global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing. Before an effective vaccine is available, the development of potential treatments for resultant coronavirus disease 2019 (COVID-19) is crucial. One of disease hallmarks is hyper-inflammatory responses, which usually leads to a severe lung disease. Patients with COVID-19 also frequently suffered from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric complications. The metabolic pathway of sphingosine-1-phosphate (S1P) is a dynamic regulator of various cell types and disease processes, including the nervous system. It has been demonstrated that S1P and its metabolic enzymes, regulating neuroinflammation and neurogenesis, exhibit important functions during viral infection. S1P receptor 1 (S1PR1) analogs including AAL-R and RP-002 inhibit pathophysiological responses at the early stage of H1N1 virus infection and then play a protective role. Fingolimod (FTY720) is an S1P receptor modulator and is being tested for treating COVID-19. Our review provides an overview of SARS-CoV-2 infection and critical role of the SphK-S1P-SIPR pathway in invasion of SARS-CoV-2 infection, particularly in the central nervous system (CNS). This may help design therapeutic strategies based on the S1P-mediated signal transduction, and the adjuvant therapeutic effects of S1P analogs to limit or prevent the interaction between the host and SARS-CoV-2, block the spread of the SARS-CoV-2, and consequently treat related complications in the CNS.

19.
Clin Exp Pharmacol Physiol ; 48(5): 637-650, 2021 May.
Article in English | MEDLINE | ID: covidwho-1075748

ABSTRACT

Global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing. Before an effective vaccine is available, the development of potential treatments for resultant coronavirus disease 2019 (COVID-19) is crucial. One of the disease hallmarks is hyper-inflammatory responses, which usually leads to a severe lung disease. Patients with COVID-19 also frequently suffer from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric complications. The metabolic pathway of sphingosine-1-phosphate (S1P) is a dynamic regulator of various cell types and disease processes, including the nervous system. It has been demonstrated that S1P and its metabolic enzymes, regulating neuroinflammation and neurogenesis, exhibit important functions during viral infection. S1P receptor 1 (S1PR1) analogues including AAL-R and RP-002 inhibit pathophysiological responses at the early stage of H1N1 virus infection and then play a protective role. Fingolimod (FTY720) is an S1P receptor modulator and is being tested for treating COVID-19. Our review provides an overview of SARS-CoV-2 infection and critical role of the SphK-S1P-SIPR pathway in invasion of SARS-CoV-2 infection, particularly in the central nervous system (CNS). This may help design therapeutic strategies based on the S1P-mediated signal transduction, and the adjuvant therapeutic effects of S1P analogues to limit or prevent the interaction between the host and SARS-CoV-2, block the spread of the SARS-CoV-2, and consequently treat related complications in the CNS.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , COVID-19/pathology , SARS-CoV-2 , Sphingosine-1-Phosphate Receptors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Sphingosine 1 Phosphate Receptor Modulators/pharmacology , Sphingosine-1-Phosphate Receptors/genetics
20.
Ann Transl Med ; 8(23): 1559, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1006755

ABSTRACT

BACKGROUND: The present study aimed to investigate the current situation and future trends of online academic activities for oncologists during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: From April 22 to May 5, 2020, a multicenter survey was conducted using an online questionnaire platform. To compare categorical variables, χ2-test, the kappa consistency analysis, and Wilcoxon rank sum test were applied. For all statistical hypotheses, P<0.05 was considered significant. RESULTS: In the present study, 2,120 oncologists participated in the survey. Of these, 2,035 respondents participated in online academic activities. During the pandemic, online academic activities significantly increased [oncologists who participated in online academic activities ≥60%: 64.58% (during the pandemic) vs. 10.90% (before the pandemic), Cohen's kappa coefficient =0.0499, P<0.001]. The findings indicated that 90.6% of respondents considered that the online academic activities would become a future trend. The main reason for the increase in online academic activities was due to in-person academic conferences and diagnoses/treatment being affected by the pandemic. Both speakers/chairs and audiences agreed that online academic activities resulted in reduced stress (61.15% vs. 67.26%, respectively; χ2=7.009, P=0.03). In the present study, 62.21% of audiences considered that the recording function of online activities was very important (score 5), while only 53.86% of the speakers had the same opinion (Z=-3.5340, P<0.001). Compared with provincial capital cities and other cities, the participants from first-tier cities thought that online academic activities required significant physical energy (χ2=6.41, P=0.040), and were more reluctant for the playback of activity contents (χ2=9.33, P=0.002) and the screenshot of activity contents (χ2=41.99, P<0.001). CONCLUSIONS: During the COVID-19 pandemic, online academic activities have become the main form of academic exchanges for oncologists. Taking full advantage of online academic activities and paying adequate attention to the participants' requirements with different roles and titles, and from different cities, are key to improving the quality of and involvement in online academic activities.

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