Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 345
Filter
Add filters

Year range
1.
Int J Mol Sci ; 21(15)2020 07 23.
Article in English | MEDLINE | ID: covidwho-670369

ABSTRACT

The role of interleukin (IL)-6 in health and disease has been under a lot of scrutiny in recent years, particularly during the recent COVID-19 pandemic. The inflammatory pathways in which IL-6 is involved are also partly responsible of the development and progression of rheumatoid arthritis (RA), opening interesting perspectives in terms of therapy. Anti-IL-6 drugs are being used with variable degrees of success in other diseases and are being tested in RA. Results have been encouraging, particularly when anti-IL-6 has been used with other drugs, such as metothrexate (MTX). In this review we discuss the main immunologic aspects that make anti-IL-6 a good candidate in RA, but despite the main therapeutic options available to target IL-6, no gold standard treatment has been established so far.


Subject(s)
Arthritis, Rheumatoid/immunology , Interleukin-6/metabolism , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Disease Progression , Humans , Interleukin-6/antagonists & inhibitors , Molecular Targeted Therapy , Signal Transduction/drug effects
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 536-541, 2020 May 28.
Article in English, Chinese | MEDLINE | ID: covidwho-745337

ABSTRACT

OBJECTIVES: Since the outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly in China and many other countries. The rapid increase in the number of cases has caused widespread panic among people and has become the main public health problem in the world. Severe patients often have difficult breathing and/or hypoxemia after 1 week of onset. A few critically ill patients may not only rapidly develop into acute respiratory distress syndrome, but also may cause coagulopathy, as well as multiple organs failure (such as heart, liver and kidney) or even death. This article is to analyze the predictive role of clinical features in patients with COVID-19 for severe disease, so as to help doctor monitor the severity-related features, restrain the disease progress, and provide a reference for improvement of medical treatment. METHODS: The clinical data of 208 patients with COVID-19 who were isolated and treated in Changsha Public Health Treatment Center from January 17, 2020 to March 14, 2020 were collected. All patients were the mild and ordinary adult patients on admission, including 105 males and 103 females from 19 to 84 (median age 44) years old. According to the "Program for the diagnosis and treatment of novel coronavirus (COVID-19) infected pneumonia (Trial version 7)" issued by the General Office of National Health Committee and Office of State Administration of Traditional Chinese Medicine as the diagnostic and typing criteria. According to progression from mild to severe disease during hospitalization, the patients were divided into a mild group (n=183) and a severe transformation group (n=25). The clinical features such as age, underlying disease, blood routine, coagulation function, blood biochemistry, oxygenation index, and so on were analyzed. Among them, laboratory tests included white blood cell (WBC), lymphocytes (LYM), neutrophil (NEU), hemoglobin (Hb), platelet (PLT), prothrombin time (PT), plasma fibrinogen (Fib), activated partial prothrombin time (APTT), thrombin time (TT), D-dimer, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Cr), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), and oxygen partial pressure in arterial blood. Partial pressure of oxygen in arterial blood/fractional concentration of inspiratory oxygen (PaO2/FiO2) was calculated. The variables with statistical significance were analyzed by logistic regression analysis. RESULTS: Patients in the severe transformation group had more combined underlying diseases than those in the mild group (P<0.05). From the perspective of disease distribution, patients in the severe transformation group had more combined hypertension (P<0.05). In the severe transformation group, PT was significantly longer, the levels of Fib, ALT, AST, CK, LDH, and CRP were significantly higher than those in the mild group (P<0.05 or P<0.001), while LYM, ALB, and PaO2/FiO2 were significantly lower than those in the mild group (P<0.05 or P<0.001). Logistic regression analysis was performed on clinical features with statistically significant differences. Combined with hypertension, LYM, PT, Fib, ALB, ALT, AST, CK, LDH, and CRP as independent variables, and having severe disease or not was the dependent variable. The results show that combined hypertension, decreased LYM, longer PT, and increased CK level were independent risk factors that affected the severity of COVID-19 (P<0.05). CONCLUSIONS: The patients with mild COVID-19 who are apt to develop severe diseases may be related to combined hypertension, decreased LYM, and longer PT, and increased CK level. For the mild patients with these clinical features, early intervention may effectively prevent the progression to severe diseases.


Subject(s)
Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adult , Aged , Aged, 80 and over , Betacoronavirus , China , Coronavirus Infections/physiopathology , Disease Progression , Female , Hospitalization , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , Retrospective Studies , Young Adult
3.
Trials ; 21(1): 758, 2020 Sep 03.
Article in English | MEDLINE | ID: covidwho-745011

ABSTRACT

OBJECTIVES: Tocilizumab is a humanized monoclonal antibody which targets and inhibits interleukin-6 (IL-6) and has demonstrated efficacy in treating diseases associated with hyper-inflammation. Data are suggestive of tocilizumab as a potential treatment for patients with COVID-19 infection. The aim of this study is to determine the safety and efficacy of standard dose versus low dose tocilizumab in adults with severe, non-critical, PCR-confirmed COVID-19 infection with evidence of progressive decline in respiratory function and evolving systemic inflammation on time to intubation, non-invasive ventilation and/or all-cause mortality. TRIAL DESIGN: This trial is a phase 2, open label, two-stage, multicentre, randomised trial. PARTICIPANTS: Adult subjects with severe, non-critical, PCR-confirmed COVID-19 infection with evidence of progressive decline in respiratory function and evolving systemic inflammation requiring admission to hospital at St. Vincent's University Hospital and Mater Misericordiae University Hospital, Dublin, Ireland. Inclusion criteria Aged 18 years or older. Confirmed SARS-CoV2 infection (as defined by positive PCR). Evidence of hyper inflammatory state as evidenced by at least three of the following: Documented temperature >38°C in the past 48 hours, IL6 >40 pg/ml, or in its absence D-dimer >1.5 µgFEU /ml, Elevated CRP (>100mg/L) and/or a three-fold increase since presentation, Elevated ferritin X5 ULN, Elevated LDH (above the ULN), Elevated fibrinogen (above the ULN). Pulmonary infiltrates on chest imaging. Moderate to severe respiratory failure as defined by PaO2/FiO2≤300mmHg. INTERVENTION AND COMPARATOR: Intervention for participants in this trial is SOC plus Tocilizumab compared to SOC alone (comparator). For Stage 1, following randomisation, subjects will receive either (Arm 1) SOC alone or (Arm 2) SOC plus Tocilizumab (standard single dose - 8mg/kg, infused over 60 minutes. Once stage 1 has fully recruited, subsequent participants will be enrolled directly into Stage 2 and receive either (Arm 1) SOC plus Tocilizumab (standard single dose - 8mg/kg, infused over 60 minutes or (Arm 2) SOC plus Tocilizumab (standard single dose - 4mg/kg, infused over 60 minutes). MAIN OUTCOMES: The primary endpoint for this study is the time to a composite primary endpoint of progression to intubation and ventilation, non-invasive ventilation or death within 28 days post randomisation. RANDOMISATION: Eligible patients will be randomised (1:1) using a central register. Randomisation will be performed through an interactive, web-based electronic data capturing database. In stage 1, eligible participants will be randomised (1:1) to (Arm 1) SOC alone or to (Arm 2) SOC with single dose (8mg/kg, maximum 800mg) intravenous tocilizumab infused over 60 minutes. In stage 2, eligible participants will be randomised (1:1) to receive either (Arm 1) single, standard dose (8mg/kg, maximum 800mg) intravenous tocilizumab infused over 60 minutes or (Arm 2) reduced dose (4mg/kg, maximum 800mg) intravenous tocilizumab infused over 60 minutes. BLINDING: This study is open label. The study will not be blinded to investigators, subjects, or medical or nursing staff. The trial statistician will be blinded for data analysis and will be kept unaware of treatment group assignments. To facilitate this, the randomisation schedule will be drawn up by an independent statistician and objective criteria were defined for the primary outcome to minimize potential bias. NUMBERS TO BE RANDOMISED: In stage 1, 90 subjects will be randomised 1:1, 45 to SOC and 45 subjects to SOC plus Tocilizumab (8mg/kg, infused over 60 minutes). In stage 2, sample size calculation for the dose evaluation stage will use data generated from stage 1 using the same primary endpoint as in stage 1. TRIAL STATUS: The COVIRL002 trial (Protocol version 1.4, 13th May 2020) commenced in May 2020 at St. Vincent's University Hospital and Mater Misericordiae University Hospital, Dublin, Ireland. Recruitment is proceeding with the aim to achieve the target sample size on or before April 2021. TRIAL REGISTRATION: COVIRL002 was registered 25 June 2020 under EudraCT number: 2020-001767-86 and Protocol identification: UCDCRC/20/02. FULL PROTOCOL: The full protocol for COVIRL002 is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Betacoronavirus/pathogenicity , Clinical Trials, Phase II as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Disease Progression , Host Microbial Interactions , Humans , Intubation, Intratracheal , Ireland , Multicenter Studies as Topic , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Respiration, Artificial , Severity of Illness Index , Time Factors , Treatment Outcome
4.
Cardiovasc Ther ; 2020: 9059562, 2020.
Article in English | MEDLINE | ID: covidwho-740295

ABSTRACT

Background: Information regarding the impact of cardiovascular (CV) conditions on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited. Methods: This study evaluated the association of underlying CV conditions with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to the designated hospital for intensive care due to COVID-19 disease progression. The patients were divided into with and without CV conditions as well as stable and intensive care groups. Results: Of the 332 patients with mild COVID-19, the median age was 51 years (IQR, 40-59 years), and 200 (61.2%) were female. Of the 48 (14.5%) patients with CV conditions, 23 (47.9%) progressed to severe disease status and required intensive care. Compared with patients without CV conditions, patients with CV conditions were older and more likely to have fatigue, chest tightness, and myalgia. The rate of requiring intensive care was significantly higher among patients with CV conditions than in patients without CV conditions (47.92% vs. 12.4%; P < 0.001). In subgroup analysis, the rate of requiring intensive care was also higher among patients with either hypertension or coronary heart disease (CHD) than in patients without hypertension or CHD. The multivariable regression model showed that CV condition served as an independent risk factor for intensive care (odds ratio (OR), 2.652 (95% CI, 1.019-6.899)) after adjustment for various cofounders. Conclusions: Patients with mild COVID-19 complicating CV conditions are susceptible to develop severe disease status and requirement for intensive care.


Subject(s)
Betacoronavirus , Cardiovascular Diseases/complications , Coronavirus Infections/complications , Critical Care , Pneumonia, Viral/complications , Adult , Disease Progression , Female , Humans , Male , Middle Aged , Pandemics
5.
Medicine (Baltimore) ; 99(35): e21804, 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740204

ABSTRACT

INTRODUCTION: Pneumonia is one of the most important characteristics of coronavirus disease 2019 (COVID-19) and imaging findings of COVID-19 pneumonia are diverse and change over disease course. However, the detailed clinical course of organizing pneumonia (OP) caused by COVID-19 has not been clarified. PATIENT CONCERNS: A 60-year-old man and a 61-year-old woman diagnosed with mild COVID-19 were admitted to our hospital. Their respiratory symptoms were deteriorating even after initiating treatment with antiviral drugs. DIAGNOSIS: Chest X-rays and computed tomography scan showed a rapid progression of linear consolidation with reversed halo sign, distributed in subpleural and peri-bronchial regions. They also presented with pulmonary fibrosis findings, including traction bronchiectasis and marked lung volume reduction. They were diagnosed with rapidly progressing OP. INTERVENTIONS: They were treated with systemic corticosteroids. OUTCOMES: The patients' imaging findings and respiratory conditions improved rapidly without any adverse effects. CONCLUSION: Physicians should carefully monitor patients with COVID-19, as they can develop rapidly progressive and fibrotic OP, which respond to corticosteroids.


Subject(s)
Coronavirus Infections , Lung , Pandemics , Pneumonia, Viral , Prednisolone/administration & dosage , Pulmonary Fibrosis , Antiviral Agents/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Disease Progression , Dose-Response Relationship, Drug , Female , Glucocorticoids/administration & dosage , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/etiology , Tomography, X-Ray Computed/methods , Treatment Outcome
6.
BMC Infect Dis ; 20(1): 640, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-736377

ABSTRACT

BACKGROUND: The COVID-19 pandemic has affected the world deeply, with more than 14,000,000 people infected and nearly 600,000 deaths. This review aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of the COVID-19 pandemic. METHODS: We scoped for relevant literatures published during 1st December 2019 to 16th July 2020 based on three databases using English and Chinese languages. We reviewed and analyzed the relevant outcomes. RESULTS: The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS and involved 4 stages of evolution. The basic reproduction number (R0) is 3.32 (95% CI:3.24-3.39), the incubation period was 5.24 days (95% CI:3.97-6.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1-39.0 °C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 °C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 65 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region. CONCLUSIONS: We provided a bird's-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease's future research, control and prevention.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Lymphopenia/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Respiratory Distress Syndrome, Adult/epidemiology , Age Factors , Aged , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Cough/epidemiology , Demography , Disease Progression , Dyspnea/epidemiology , Fatigue/epidemiology , Female , Fever/epidemiology , Humans , Laboratories , Male , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , Risk Factors , Sex Factors , Tomography, X-Ray Computed
7.
PLoS One ; 15(8): e0238090, 2020.
Article in English | MEDLINE | ID: covidwho-733001

ABSTRACT

In the article a virus transmission model is constructed on a simplified social network. The social network consists of more than 2 million nodes, each representing an inhabitant of Slovenia. The nodes are organised and interconnected according to the real household and elderly-care center distribution, while their connections outside these clusters are semi-randomly distributed and undirected. The virus spread model is coupled to the disease progression model. The ensemble approach with the perturbed transmission and disease parameters is used to quantify the ensemble spread, a proxy for the forecast uncertainty. The presented ongoing forecasts of COVID-19 epidemic in Slovenia are compared with the collected Slovenian data. Results show that at the end of the first epidemic wave, the infection was twice more likely to transmit within households/elderly care centers than outside them. We use an ensemble of simulations (N = 1000) and data assimilation approach to estimate the COVID-19 forecast uncertainty and to inversely obtain posterior distributions of model parameters. We found that in the uncontrolled epidemic, the intrinsic uncertainty mostly originates from the uncertainty of the virus biology, i.e. its reproduction number. In the controlled epidemic with low ratio of infected population, the randomness of the social network becomes the major source of forecast uncertainty, particularly for the short-range forecasts. Virus transmission models with accurate social network models are thus essential for improving epidemics forecasting.


Subject(s)
Computer Simulation , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Social Networking , Basic Reproduction Number , Betacoronavirus , Coronavirus Infections/epidemiology , Disease Progression , Family Characteristics , Forecasting , Humans , Models, Theoretical , Pandemics , Pneumonia, Viral/epidemiology , Slovenia/epidemiology , Uncertainty
9.
Emerg Microbes Infect ; 9(1): 1869-1877, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-730432

ABSTRACT

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered for them. After identifying the possible markers for the therapeutic window, we then divided the patients, based on whether they were treated with corticosteroids within the therapeutic window, into the early-start group and control group. We identified that the therapeutic window for corticosteroids was characterized by a marked radiographic progression and lactase dehydrogenase (LDH) less than two times the upper limit of normal (ULN). The Shanghai cohort comprised of 68 patients, including 47 in the early-start group and 21 in the control group. The proportion of patients requiring invasive mechanical ventilation was significantly lower in the early-start group than in the control group (10.6% vs. 33.3%, difference, 22.7%, 95% confidence interval 2.6-44.8%). Among the validation cohort of 51 patients, similar difference of the primary outcome was observed (45.0% vs. 74.2%, P = 0.035). Among COVID-19 patients with marked radiologic progression, short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Adrenal Cortex Hormones/administration & dosage , Biomarkers , Cohort Studies , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Disease Progression , Humans , Inflammation/prevention & control , L-Lactate Dehydrogenase/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , Radiography , Reproducibility of Results , Respiration, Artificial , Respiratory Distress Syndrome, Adult/etiology , Treatment Outcome
10.
PLoS One ; 15(8): e0237832, 2020.
Article in English | MEDLINE | ID: covidwho-729563

ABSTRACT

This paper analyses the evolution of COVID-19 in Cameroon over the period March 6-April 2020 using SIR models. Specifically, we 1) evaluate the basic reproduction number of the virus, 2) determine the peak of the infection and the spread-out period of the disease, and 3) simulate the interventions of public health authorities. Data used in this study is obtained from the Cameroonian Public Health Ministry. The results suggest that over the identified period, the reproduction number of COVID-19 in Cameroon is about 1.5, and the peak of the infection should have occurred at the end of May 2020 with about 7.7% of the population infected. Furthermore, the implementation of efficient public health policies could help flatten the epidemic curve.


Subject(s)
Basic Reproduction Number , Coronavirus Infections/epidemiology , Disease Progression , Pneumonia, Viral/epidemiology , Algorithms , Betacoronavirus , Cameroon/epidemiology , Computer Simulation , Coronavirus Infections/prevention & control , Humans , Likelihood Functions , Models, Statistical , Pandemics/prevention & control , Pneumonia, Viral/prevention & control
11.
PLoS One ; 15(8): e0237959, 2020.
Article in English | MEDLINE | ID: covidwho-723992

ABSTRACT

Current geographic spread of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections shows heterogeneity. This study explores the role of age in potentially driving differentials in infection spread, epidemic potential, and rates of disease severity and mortality across countries. An age-stratified deterministic mathematical model that describes SARS-CoV-2 transmission dynamics was applied to 159 countries and territories with a population ≥1 million. Assuming worst-case scenario for the pandemic, the results indicate that there could be stark regional differences in epidemic trajectories driven by differences in the distribution of the population by age. In the African Region (median age: 18.9 years), the median R0 was 1.05 versus 2.05 in the European Region (median age: 41.7 years), and the median (per 100 persons) for the final cumulative infection incidence was 22.5 (versus 69.0), for severe and/or critical disease cases rate was 3.3 (versus 13.0), and for death rate was 0.5 (versus 3.9). Age could be a driver of variable SARS-CoV-2 epidemic trajectories worldwide. Countries with sizable adult and/or elderly populations and smaller children populations may experience large and rapid epidemics in absence of interventions. Meanwhile, countries with predominantly younger age cohorts may experience smaller and slower epidemics. These predictions, however, should not lead to complacency, as the pandemic could still have a heavy toll nearly everywhere.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Models, Theoretical , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Coronavirus Infections/mortality , Coronavirus Infections/virology , Disease Progression , Disease Transmission, Infectious , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Mortality , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Severity of Illness Index , Young Adult
14.
Gac Med Mex ; 156(4): 339-343, 2020.
Article in English | MEDLINE | ID: covidwho-719927

ABSTRACT

The disease caused by the new SARS-CoV-2 coronavirus (COVID-19) spread rapidly from China to the entire world. Approximately one third of SARS-CoV-2-infected patients have neurological disorders, especially those classified as severe cases and that require mechanical ventilation. On the other hand, almost nine out of 10 patients admitted to an Intensive Care Unit could not breathe spontaneously, thus requiring invasive and non-invasive ventilatory support. So far, whether early neurological disorders such as hyposmia or anosmia, dysgeusia or ageusia, headache and vertigo are significant in the progression to the severe form of the disease or whether they are related to entry to the central nervous system via peripheral nerves has not been determined. Considering the great similarity between SARS-CoV and SARS-CoV-2, and that the severity of the condition that leads to death cannot be explained solely by lung involvement, it is important to determine whether SARS-CoV-2 potential invasion to the central nervous system is partially responsible for the severe respiratory component observed in patients with COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Nervous System Diseases/virology , Pneumonia, Viral/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Progression , Humans , Intensive Care Units/statistics & numerical data , Nervous System Diseases/epidemiology , Nervous System Diseases/physiopathology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Respiration, Artificial/statistics & numerical data , Severity of Illness Index , Viral Tropism
15.
Clin Infect Dis ; 71(15): 723-731, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-719209

ABSTRACT

BACKGROUND: Our objective was to retrospectively analyze the evolution of clinical features and thin-section computed tomography (CT) imaging of novel coronavirus disease 2019 (COVID-19) pneumonia in 17 discharged patients. METHODS: Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and a CT pattern were documented in all patients during the 4 weeks after admission. A CT score was used to evaluate the extent of the disease. RESULTS: There were marked improvements of fever, lymphocyte counts, C-reactive proteins, and erythrocyte sedimentation rates within the first 2 weeks after admission. However, the mean CT score rapidly increased from the first to the third week, with a top score of 8.2 obtained in the second week. During the first week, the main CT pattern was ground-glass opacities (GGO; 76.5%). The frequency of GGO (52.9%) decreased in the second week. Consolidation and mixed patterns (47.0%) were noted in the second week. Thereafter, consolidations generally dissipated into GGO, and the frequency of GGO increased in the third week (76.5%) and fourth week (71.4%). Opacities were mainly located in the peripheral (76.5%) and subpleural (47.1%) zones of the lungs; they presented as focal (35.3%) or multifocal (29.4%) in the first week and became more diffuse in the second (47.1%) and third weeks (58.8%), then showed a reduced extent in fourth week (50%). CONCLUSIONS: The progression course of the CT pattern was later than the progression of the clinical parameters within the first 2 weeks after admission; however, there were synchronized improvements in both the clinical and radiologic features in the fourth week.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Pneumonia/pathology , Adult , Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Disease Progression , Female , Fever/pathology , Fever/virology , Hospitalization , Humans , Lung/pathology , Lung/virology , Male , Middle Aged , Pandemics , Patient Discharge , Pneumonia/virology , Pneumonia, Viral/virology , Retrospective Studies , Tomography, X-Ray Computed/methods
16.
Invest Ophthalmol Vis Sci ; 61(10): 29, 2020 08 03.
Article in English | MEDLINE | ID: covidwho-717438

ABSTRACT

Purpose: This systematic review aimed to determine currently reported clinical and prodromal ocular symptoms in patients with coronavirus disease 2019 (COVID-19). Methods: An online article search was performed in PubMed and EMBASE. Altogether 15 studies (retrospective, prospective, or case studies) involving 1533 patients with COVID-19, reporting on ocular symptoms, and with outcome data available were identified. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Study-specific estimates (incidence rates of ocular symptoms in patients with COVID-19) of cases were combined using one-group meta-analysis in a random-effects model. Results: Of all included studies, 11.2% (95% confidence interval, 5.5-16.9; 78/1526 cases) reported ocular symptoms. The most common ocular finding was conjunctivitis. Prodromal ocular symptoms occurred in 12.5% (13/104 cases) of patients with COVID-19. Positive real-time polymerase chain reaction results were obtained for 16.7% (10/60 cases) of conjunctival samples and 0% (0/17 cases) of tear samples. Twelve ocular conjunctival swab samples tested positive for SARS-CoV-2. Ten cases were from subjects showing ocular symptoms (16.7%, 10/60 cases), and the remaining two cases were from subjects without ocular manifestation (1.8%, 2/113 cases). Limitations included the short study period, small sample size, findings were limited to the Asian population, only seven articles included ophthalmologic examination details, and there is currently no consensus on COVID-19 management. Conclusions: Ocular symptoms may occur in the presymptomatic phase as a prodromal symptom (12.5%, 13/104 cases), suggesting the possibility of viral transmission from the conjunctiva.


Subject(s)
Conjunctivitis, Viral/epidemiology , Coronavirus Infections/epidemiology , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Prodromal Symptoms , Severe Acute Respiratory Syndrome/diagnosis , Clinical Laboratory Techniques/methods , Conjunctivitis, Viral/diagnosis , Coronavirus Infections/diagnosis , DNA, Viral/analysis , Disease Progression , Female , Humans , Incidence , Male , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Prognosis , Real-Time Polymerase Chain Reaction/methods , Risk Assessment , Severe Acute Respiratory Syndrome/epidemiology
17.
Signal Transduct Target Ther ; 5(1): 156, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-717099

ABSTRACT

The global Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has affected more than eight million people. There is an urgent need to investigate how the adaptive immunity is established in COVID-19 patients. In this study, we profiled adaptive immune cells of PBMCs from recovered COVID-19 patients with varying disease severity using single-cell RNA and TCR/BCR V(D)J sequencing. The sequencing data revealed SARS-CoV-2-specific shuffling of adaptive immune repertories and COVID-19-induced remodeling of peripheral lymphocytes. Characterization of variations in the peripheral T and B cells from the COVID-19 patients revealed a positive correlation of humoral immune response and T-cell immune memory with disease severity. Sequencing and functional data revealed SARS-CoV-2-specific T-cell immune memory in the convalescent COVID-19 patients. Furthermore, we also identified novel antigens that are responsive in the convalescent patients. Altogether, our study reveals adaptive immune repertories underlying pathogenesis and recovery in severe versus mild COVID-19 patients, providing valuable information for potential vaccine and therapeutic development against SARS-CoV-2 infection.


Subject(s)
B-Lymphocytes/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Immunity, Cellular , Immunity, Humoral , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Antigens, Viral/genetics , Antigens, Viral/immunology , B-Lymphocytes/classification , B-Lymphocytes/virology , Betacoronavirus/immunology , Case-Control Studies , China , Convalescence , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Disease Progression , Gene Expression , High-Throughput Nucleotide Sequencing , Host-Pathogen Interactions/immunology , Humans , Immunologic Memory , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Receptors, Antigen, B-Cell/classification , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/classification , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Severity of Illness Index , Single-Cell Analysis , T-Lymphocytes/classification , T-Lymphocytes/virology
18.
Emerg Microbes Infect ; 9(1): 1869-1877, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-713723

ABSTRACT

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered for them. After identifying the possible markers for the therapeutic window, we then divided the patients, based on whether they were treated with corticosteroids within the therapeutic window, into the early-start group and control group. We identified that the therapeutic window for corticosteroids was characterized by a marked radiographic progression and lactase dehydrogenase (LDH) less than two times the upper limit of normal (ULN). The Shanghai cohort comprised of 68 patients, including 47 in the early-start group and 21 in the control group. The proportion of patients requiring invasive mechanical ventilation was significantly lower in the early-start group than in the control group (10.6% vs. 33.3%, difference, 22.7%, 95% confidence interval 2.6-44.8%). Among the validation cohort of 51 patients, similar difference of the primary outcome was observed (45.0% vs. 74.2%, P = 0.035). Among COVID-19 patients with marked radiologic progression, short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Adrenal Cortex Hormones/administration & dosage , Biomarkers , Cohort Studies , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Disease Progression , Humans , Inflammation/prevention & control , L-Lactate Dehydrogenase/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , Radiography , Reproducibility of Results , Respiration, Artificial , Respiratory Distress Syndrome, Adult/etiology , Treatment Outcome
19.
Clin Immunol ; 219: 108572, 2020 10.
Article in English | MEDLINE | ID: covidwho-713545

ABSTRACT

Human Leukocyte Antigen (HLA) includes a large set of genes with important actions in immune response against viral infection. Numerous studies have revealed the existence of significant associations between certain HLA alleles and the susceptibility and prognosis of different infectious diseases. In this pilot study we analyse the binding affinity between 66 class I HLA alleles and SARS-CoV-2 viral peptides, and its association with the severity of the disease. A total of 45 Spanish patients with mild, moderate and severe SARS-CoV-2 infection were typed for HLA class I; after that, we analysed if an in silico model of HLA I-viral peptide binding affinity and classical HLA supertypes could be correlated to the severity of the disease. Our results suggest that patients with mild disease present Class I HLA molecules with a higher theoretical capacity for binding SARS-Cov-2 peptides and showed greater heterozygosity when comparing them with moderate and severe groups. In this regard, identifying HLA-SARS-CoV-2 peptides binding differences between individuals would help to clarify the heterogeneity of clinical responses to the disease and will also be useful to guide a personalized treatment according to its particular risk.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Histocompatibility Antigens Class I/genetics , Host-Pathogen Interactions/immunology , Pneumonia, Viral/genetics , Viral Proteins/genetics , Adult , Aged , Alleles , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Disease Progression , Female , Gene Expression , Gene Frequency , Histocompatibility Antigens Class I/classification , Histocompatibility Antigens Class I/immunology , Humans , Immunity, Innate , Male , Middle Aged , Pandemics , Peptides/genetics , Peptides/immunology , Pilot Projects , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Binding , Severity of Illness Index , Spain , Viral Proteins/immunology
20.
Oncology (Williston Park) ; 34(8): 317-319, 2020 08 12.
Article in English | MEDLINE | ID: covidwho-713075

ABSTRACT

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.


Subject(s)
Anticoagulants/therapeutic use , Bone Neoplasms/drug therapy , Coronavirus Infections/therapy , Palliative Care , Pneumonia, Viral/therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Respiratory Insufficiency/therapy , Aged , Androgen Antagonists/therapeutic use , Androstenes/therapeutic use , Antineoplastic Agents/therapeutic use , Betacoronavirus , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/complications , Bone Neoplasms/secondary , Cancer Pain/complications , Cancer Pain/therapy , Coronavirus Infections/complications , Disease Progression , Docetaxel/therapeutic use , Drug Combinations , Eligibility Determination , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Intensive Care Units/supply & distribution , Lopinavir/therapeutic use , Male , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/complications , Prostatic Neoplasms, Castration-Resistant/complications , Prostatic Neoplasms, Castration-Resistant/pathology , Renal Insufficiency , Respiratory Insufficiency/etiology , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/therapeutic use , Severity of Illness Index , Zoledronic Acid/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL