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1.
Clinical Microbiology and Infection ; 2020.
Article | WHO COVID | ID: covidwho-802088

ABSTRACT

Objectives Use of corticosteroids is common in the treatment of coronavirus disease 2019, but the clinical effectiveness was controversial We aimed to investigate the association of corticosteroids therapy with clinical outcomes of hospitalized COVID-19 patients Methods In this single center, retrospective cohort study, adult patients with confirmed coronavirus disease 2019 and dead or discharged between December 29, 2019 and February 15, 2020 were studied 1:1 propensity score matchings were performed between patients with or without corticosteroids treatment Multivariable COX proportional hazards model was used to estimate the association between corticosteroids treatment and in-hospital mortality by taking corticosteroids as a time-varying covariate Results Among 646 patients, in-hospital death rate was higher in 158 patients with corticosteroids administration (72/158, 45 6% vs 56/488, 11 5%, p<0 0001) After propensity score-match analysis, no significant differences were observed in in-hospital death between patients with and without corticosteroids treatment (47/124, 37 9% vs 47/124, 37 9%, p=1 000) When patients received corticosteroids before they required nasal high-flow oxygen therapy or mechanical ventilation, in-hospital death rate was lower than that in patients who were not administered with corticosteroids (17/86, 19 8% vs 26/86, 30 2%, log rank p=0 0102), whereas time from admission to clinical improvement was longer (13 [IQR, 10∼17] days vs 10 [IQR, 8∼13] days;p<0 001) Using Cox proportional hazards regression model accounting for time varying exposures in matched pairs, corticosteroid therapy was not associated with mortality difference (HR=0 98, 95%CI: 0 93-1 03, p=0 4694) Conclusions Corticosteroids use in COVID-19 patients may not be associated with in-hospital mortality

4.
Int J Infect Dis ; 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-758908

ABSTRACT

BACKGROUND: To figure out whether abnormal coagulation parameters are associated with disease severity and poor prognosis in patients with 2019 Corona Virus Disease (COVID-19). METHODS: A systematic literature search was conducted using the databases PubMed, Embase, and Web of sciences until April 25, 2020. We included a total of 15 studies with 2277 patients. Platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D) and fibrinogen (FIB) were collected and analyzed. The statistical results were expressed the effect measure by mean difference (MD) with the related 95% confidence interval (CI). RESULTS: The PLT level of severe patients was lower than that of mild patients, while the levels of PT, D-D and FIB were higher than those of mild patients (P < 0.05). The level of APTT had no statistical difference between two groups (P > 0.05). Compared to Non-ICU patients, PT of ICU patients was significantly longer (P < 0.05). In Non-survivors, PT and D-D were higher, yet PLT was lower than survivors (P < 0.05). There was no significant difference in APTT between survivors and Non-survivors (P > 0.05). The funnel plot and Egger's Regression test demonstrated that there was no publication bias. CONCLUSIONS: Our data support the notion that coagulopathy could be considered as a risk factor for disease severity and mortality of COVID-19, which may help clinicians to identify the incidence of poor outcomes in COVID-19 patients.

5.
J Hematol Oncol ; 13(1): 120, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-744994

ABSTRACT

BACKGROUND: Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. METHODS: Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. RESULTS: We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates. Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation. CONCLUSIONS: Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2. SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.


Subject(s)
Betacoronavirus/metabolism , Blood Platelets/metabolism , Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Thrombosis/metabolism , Adult , Aged , Animals , Betacoronavirus/genetics , Caco-2 Cells , Coronavirus Infections/virology , Female , HeLa Cells , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Middle Aged , PC-3 Cells , Pandemics , Peptidyl-Dipeptidase A/genetics , Platelet Aggregation/immunology , Platelet Count , Pneumonia, Viral/virology , RNA, Viral/blood , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Thrombosis/virology
7.
J Epidemiol Community Health ; 2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-733144

ABSTRACT

BACKGROUND: The presymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented in limited clusters, and it is predicted through modelling. However, there is a lack of evidence from observations with a large sample size. METHODS: We used data from meticulous contact tracing of people exposed to cases of SARS-CoV-2 to estimate the proportion of cases that result from the presymptomatic transmission of the virus in Beijing during January 2020 and February 2020. RESULTS: The results showed that presymptomatic transmission occurred in at least 15% of 100 secondary COVID-19 cases. The earliest presymptomatic contact event occurred 5 days prior to the index case's onset of symptoms, and this occurred in two clusters. CONCLUSIONS: The finding suggested that the contact tracing period should be earlier and highlighted the importance of preventing transmission opportunities well before the onset of symptoms.

8.
BMC Infect Dis ; 20(1): 637, 2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-733046

ABSTRACT

BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading globally. Recently, several articles have mentioned that the early acute respiratory distress syndrome (ARDS) caused by COVID-19 significantly differ from those of ARDS due to other causes. Actually, we newly observed that some mechanically ventilated COVID-19 patients recovering from severe ARDS (more than 14 days after invasive ventilation) often experienced evidently gradual increases in CO2 retention and minute ventilation. However, the underlying mechanics remain unclear. CASE PRESENTATION: To explain these pathophysiological features and discuss the ventilatory strategy during the late phase of severe ARDS in COVID-19 patients, we first used a metabolic module on a General Electric R860 ventilator (Engstrom Carestation; GE Healthcare, USA) to monitor parameters related to gas metabolism, lung mechanics and physiological dead space in two COVID-19 patients. We found that remarkably decreased ventilatory efficiency (e.g., the ratio of dead space to tidal volume 70-80%, arterial to end-tidal CO2 difference 18-23 mmHg and ventilatory ratio 3-4) and hypermetabolism (oxygen consumption 300-400 ml/min, CO2 elimination 200-300 ml/min) may explain why these patients experienced more severe respiratory distress and CO2 retention in the late phase of ARDS caused by COVID-19. CONCLUSION: During the recovery period of ARDS among mechanically-ventilated COVID-19 patients, attention should be paid to the monitoring of physiological dead space and metabolism. Tidal volume (8-9 ml/kg) could be increased appropriately under the limited plateau pressure; however, barotrauma should still be kept in mind.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiration, Artificial , Respiratory Distress Syndrome, Adult/therapy , Aged , Coronavirus Infections/complications , Female , Humans , Monitoring, Physiologic , Oxygen Consumption , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome, Adult/etiology , Tidal Volume , Ventilators, Mechanical
9.
Clin Infect Dis ; 2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-729105

ABSTRACT

BACKGROUND: The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe COVID-19 patients were still less known. METHODS: The neutralizing antibodies (NAbs) and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and ELISA. Viral load was determined by real-time RT-PCR. A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analysed. Multivariable adjusted generalized linear mixed model for random effects were developed. RESULTS: After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-IgM, 97.8% for S-IgM, 100% for N-IgG, 100% for RBD-IgG, 91.1% for N-IgM and 91.1% for NAbs. The NAbs titers increased over time in both survivors and non-survivors and correlated to IgG antibodies against N, S and RBD, while its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% CI -3.04 to -1.18, p&0.0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, p&0.0001) and RBD-IgG (slope -1.43, 95% CI -1.98 to -0.88, p&0.0001) were negatively correlated with viral load. S-IgG titers were lower in non-survivors than survivors (p=0.020) at week 4 after symptoms onset. CONCLUSIONS: IgM, IgG against N, S and RBD and NAbs developed in most severe COVID-19 patients, and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S and RBD were related to viral clearance.

10.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-725886

ABSTRACT

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.


Subject(s)
Bacteremia/pathology , Bacterial Infections/pathology , Coronavirus Infections/pathology , Fungemia/pathology , Mycoses/pathology , Opportunistic Infections/pathology , Pneumonia, Viral/pathology , Respiratory Tract Infections/pathology , Urinary Tract Infections/pathology , Aged , Bacteremia/microbiology , Bacteremia/mortality , Bacteremia/virology , Bacterial Infections/microbiology , Bacterial Infections/mortality , Bacterial Infections/virology , Betacoronavirus/pathogenicity , Coronavirus Infections/microbiology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Critical Illness , Female , Fungemia/microbiology , Fungemia/mortality , Fungemia/virology , Fungi/pathogenicity , Gram-Negative Bacteria/pathogenicity , Gram-Positive Bacteria/pathogenicity , Humans , Intensive Care Units , Lung/microbiology , Lung/pathology , Lung/virology , Male , Middle Aged , Mycoses/microbiology , Mycoses/mortality , Mycoses/virology , Opportunistic Infections/microbiology , Opportunistic Infections/mortality , Opportunistic Infections/virology , Pandemics , Pneumonia, Viral/microbiology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Respiration, Artificial/adverse effects , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Respiratory Tract Infections/virology , Retrospective Studies , Risk , Severity of Illness Index , Survival Analysis , Urinary Tract Infections/microbiology , Urinary Tract Infections/mortality , Urinary Tract Infections/virology
11.
Crit Care Med ; 2020 Aug 19.
Article in English | MEDLINE | ID: covidwho-725837

ABSTRACT

OBJECTIVES: An ongoing outbreak of coronavirus disease 2019 is spreading globally. Acute hypoxemic respiratory failure is the most common complication of coronavirus disease 2019. However, the clinical effectiveness of early high-flow nasal oxygen treatment in patients with coronavirus disease 2019 with acute hypoxemic respiratory failure has not been explored. This study aimed to analyze the effectiveness of high-flow nasal oxygen treatment and to identify the variables predicting high-flow nasal oxygen treatment failure in coronavirus disease 2019 patients with acute hypoxemic respiratory failure. DESIGN: A multicenter, retrospective cohort study. SETTING: Three tertiary hospitals in Wuhan, China. PATIENTS: Forty-three confirmed coronavirus disease 2019 adult patients with acute hypoxemic respiratory failure treated with high-flow nasal oxygen. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age of the enrolled patients was 63.0 ± 9.7 years; female patients accounted for 41.9%. High-flow nasal oxygen failure (defined as upgrading respiratory support to positive pressure ventilation or death) was observed in 20 patients (46.5%), of which 13 (30.2%) required endotracheal intubation. Patients with high-flow nasal oxygen success had a higher median oxygen saturation (96.0% vs 93.0%; p < 0.001) at admission than those with high-flow nasal oxygen failure. High-flow nasal oxygen failure was more likely in patients who were older (p = 0.030) and male (p = 0.037), had a significant increase in respiratory rate and a significant decrease in the ratio of oxygen saturation/FIO2 to respiratory rate index within 3 days of high-flow nasal oxygen treatment. In a multivariate logistic regression analysis model, male and lower oxygen saturation at admission remained independent predictors of high-flow nasal oxygen failure. The hospital mortality rate of the cohort was 32.5%; however, the hospital mortality rate in patients with high-flow nasal oxygen failure was 65%. CONCLUSIONS: High-flow nasal oxygen may be effective for treating coronavirus disease 2019 patients with mild to moderate acute hypoxemic respiratory failure. However, high-flow nasal oxygen failure was associated with a poor prognosis. Male and lower oxygenation at admission were the two strong predictors of high-flow nasal oxygen failure.

12.
Evid Based Complement Alternat Med ; 2020: 5818107, 2020.
Article in English | MEDLINE | ID: covidwho-721222

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) outbreak in Wuhan, China, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anisodamine hydrobromide injection (AHI), the main ingredient of which is anisodamine, is a listed drug for improving microcirculation in China. Anisodamine can improve the condition of patients with COVID-19. Materials and Methods: Protein-protein interactions obtained from the String databases were used to construct the protein interaction network (PIN) of AHI using Cytoscape. The crucial targets of AHI PIN were screened by calculating three topological parameters. Gene ontology and pathway enrichment analyses were performed. The intersection between the AHI component proteins and angiotensin-converting enzyme 2 (ACE2) coexpression proteins was analyzed. We further investigated our predictions of crucial targets by performing molecular docking studies with anisodamine. Results: The PIN of AHI, including 172 nodes and 1454 interactions, was constructed. A total of 54 crucial targets were obtained based on topological feature calculations. The results of Gene Ontology showed that AHI could regulate cell death, cytokine-mediated signaling pathways, and immune system processes. KEGG disease pathways were mainly enriched in viral infections, cancer, and immune system diseases. Between AHI targets and ACE2 coexpression proteins, 26 common proteins were obtained. The results of molecular docking showed that anisodamine bound well to all the crucial targets. Conclusion: The network pharmacological strategy integrated molecular docking to explore the mechanism of action of AHI against COVID-19. It provides protein targets associated with COVID-19 that may be further tested as therapeutic targets of anisodamine.

14.
Nature ; 2020 Aug 05.
Article in English | MEDLINE | ID: covidwho-703377

ABSTRACT

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the global coronavirus infectious disease (COVID-19) public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved the expression and immunogenicity of betacoronavirus spike proteins1. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant2 SARS-CoV-2 and CD8 T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in Phase 3 efficacy evaluation.

15.
Journal of Clinical Biochemistry and Nutrition ; 2020.
Article | WHO COVID | ID: covidwho-696922
16.
SSRN ; 2020.
Article | WHO COVID | ID: covidwho-693326

ABSTRACT

Biotin-labeled molecular probes, comprising specific regions of the SARS-CoV-2 spike, would be helpful in the isolation and characterization of antibodies targeting this recently emerged pathogen To develop such probes, we designed constructs incorporating an N-terminal purification tag, a site-specific protease-cleavage site, the probe region of interest, and a C-terminal sequence targeted by biotin ligase Probe regions included full-length spike ectodomain as well as various subregions, and we also designed mutants to eliminate recognition of the ACE2 receptor Yields of biotin-labeled probes from transient transfection ranged from ~0 5 mg/L for the complete ectodomain to >5 mg/L for several subregions Probes were characterized for antigenicity and ACE2 recognition, and the structure of the spike ectodomain probe was determined by cryo-electron microscopy We also characterized antibody-binding specificities and cell-sorting capabilities of the biotinylated probes Altogether, structure-based design coupled to efficient purification and biotinylation processes can thus enable streamlined development of SARS-CoV-2 spike-ectodomain probes Funding: Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID) Support for this work was also provided by COVID-19 Fast Grants, the Jack Ma Foundation, the Self Graduate Fellowship Program, and NIH grants DP5OD023118, R21AI143407, and R21AI144408 Some of this work was performed at the Columbia University Cryo-EM Center at the Zuckerman Institute, and some at the Simons Electron Microscopy Center (SEMC) and National Center for Cryo-EM Access and Training (NCCAT) located at the New York Structural Biology Center, supported by grants from the Simons Foundation (SF349247), NYSTAR, and the NIH National Institute of General Medical Sciences (GM103310) Conflict of Interest: The authors declare that they have no conflict of interest Ethical Approval: Peripheral blood mononuclear cells (PBMCs) for B cell sorting were obtained from a convalescent SARS-CoV-2 patient (collected 75 days post symptom onset under an IRB approved clinical trial protocol, VRC 200 - ClinicalTrials gov Identifier: NCT00067054) and a healthy control donor from the NIH blood bank pre-SARS-CoV-2 pandemic

17.
Chin. Trad. Herbal Drugs ; 12(51): 3201-3210, 20200628.
Article in Chinese | ELSEVIER | ID: covidwho-684124

ABSTRACT

Objective: To investigate the mechanism of Qingkailing Injection in the treatment of coronavirus disease 2019 (COVID-19). Methods: The active components and target proteins of Gardeniae Fructus, Isatidis Radix, Lonicerae Japonicae Flos, and other materials in Qingkailing Injection were obtained by means of literature search and TCMSP. Uniprot database was used to search the target genes corresponding to the active ingredients, and Cytoscape 3.7.2 was used to construct the drug-compound-target network. The enrichment analysis of KEGG pathway was carried out with the help of DAVID database to predict its mechanism. Core active components and potential targets of anti-COVID-19 drugs were verified by molecular docking. Results: The drug-compound- target network consisted of five drugs, 62 compounds and 70 targets. The KEGG pathway enrichment analysis included 41 signaling pathways (P < 0.05), which were mainly involved in cell apoptosis, Fc epsilon RI signaling pathway, TNF signaling pathway, etc. Molecular docking results showed that acacetin and syrigin had strong affinity with potential targets of anti-COVID-19 drugs. Conclusion: In this study, the effect of Qingkailing Injection has the characteristics of multiple components, multiple targets and multiple pathways. The active component, acacetin, can regulate the apoptosis pathway and TNF pathway by acting on CASP3, CASP8, FASLG, and other targets, so as to realize the potential therapeutic effect on COVID-19.

18.
Signal Transduct Target Ther ; 5(1): 128, 2020 07 25.
Article in English | MEDLINE | ID: covidwho-680767

ABSTRACT

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections , Disease Outbreaks , Immunity, Innate , Immunotherapy , Pandemics , Pneumonia, Viral , Shock, Septic , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Cytokines/immunology , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Shock, Septic/epidemiology , Shock, Septic/immunology , Shock, Septic/therapy
19.
N Engl J Med ; 2020 07 28.
Article in English | MEDLINE | ID: covidwho-680559

ABSTRACT

BACKGROUND: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. METHODS: Nonhuman primates received 10 or 100 µg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. RESULTS: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-µg dose group and 3481 in the 100-µg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-µg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. CONCLUSIONS: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).

20.
Kidney Blood Press Res ; 45(4): 612-622, 2020.
Article in English | MEDLINE | ID: covidwho-680430

ABSTRACT

INTRODUCTION: Severe acute respiratory viral infections are frequency accompanied by multiple organ dysfunction, including acute kidney injury (AKI). In December 2019, the coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, Hubei Province, China, and rapidly spread worldwide. While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described. We assessed the incidence and clinical characteristics of AKI in patients with laboratory-confirmed COVID-19 and its effects on clinical outcomes. METHODS: We conducted a multicenter, retrospective, observational study of patients with COVID-19 admitted to two general hospitals in Wuhan from 5 January 2020 to 21 March 2020. Demographic data and information on organ dysfunction were collected daily. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 72 h after admission or after 72 h, respectively. RESULTS: Of the 116 patients, AKI developed in 21 (18.1%) patients. Among them, early and late AKI were found in 13 (11.2%) and 8 (6.9%) patients, respectively. Compared with patients without AKI, patients with AKI had more severe organ dysfunction, as indicated by a higher level of disease severity status, higher sequential organ failure assessment (SOFA) score on admission, an increased prevalence of shock, and a higher level of respiratory support. Patients with AKI had a higher SOFA score on admission (4.5 ± 2.1 vs. 2.8 ± 1.4, OR 1.498, 95% CI 1.047-2.143 ) and greater hospital mortality (57.1% vs. 12.6%, OR 3.998, 95% CI 1.088-14.613) than patients without AKI in both the univariate and multivariate analyses. Patients with late AKI, but not those with early AKI, had a significantly prolonged length of stay (19.6 vs. 9.6 days, p = 0.015). CONCLUSION: Our findings show that admission SOFA score was an independent risk factor for AKI in COVID-19 patients, and patients with AKI had higher in-hospital mortality. Moreover, AKI development after 72 h of admission was related to prolonged hospitalization time.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Coronavirus Infections/complications , Pneumonia, Viral/complications , Acute Kidney Injury/mortality , Adult , Aged , Aged, 80 and over , China/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Disease Progression , Female , Hospital Mortality , Hospitals, General , Humans , Incidence , Kidney Function Tests , Length of Stay , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/therapy , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Retrospective Studies , Treatment Outcome , Water-Electrolyte Balance
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