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1.
Front Physiol ; 12: 653985, 2021.
Article in English | MEDLINE | ID: covidwho-1526787

ABSTRACT

The renin angiotensin system and the cholinergic anti-inflammatory pathway have been recently shown to modulate lung inflammation in patients with COVID-19. We will show how studies performed on this disease are starting to provide evidence that these two anti-inflammatory systems may functionally interact with each other, a mechanism that could have a more general physiological relevance than only COVID-19 infection.

2.
CNS Neurol Disord Drug Targets ; 20(5): 473-477, 2021.
Article in English | MEDLINE | ID: covidwho-1526730

ABSTRACT

INTRODUCTION: Catatonia is a psychomotor syndrome that presents with severe symptoms which can lead to dangerous and lethal conditions if not diagnosed and treated properly. SARS-- CoV-2 is a positive-sense single-stranded RNA virus that can occur in severe cases with acute pneumonia, ARDS, sepsis and septic shock. In these cases, ICU admission is necessary. CASE SUMMARY: A 59-year-old Caucasian man with septic shock and bilateral interstitial pneumonia from SARS-CoV-2 and schizotypal personality disorder presented with catatonic behaviour manifested by soporous state, response to intense painful stimuli with the opening of the eyes, execution of simple verbal commands, maintenance of the same position, catalepsy, immobility, rigidity and mutism. At the same time, there were symptoms of septic shock and catatonic symptoms, causing greater difficulty in the correct formulation of the diagnosis. During the course of his hospitalization, he was treated with asenapine 20 mg/day. The catatonia responded rapidly and significantly to the asenapine. DISCUSSION: To date, the pathophysiology of catatonia is unclear, and few guidelines are available for the treatment of catatonia. In the literature, studies have reported the efficacy of benzodiazepines such as lorazepam and diazepam, GABAA agonists such as zolpidem, NMDA receptor antagonists such as memantine, antidepressant SSRIs such as fluoxetine and paroxetine, and antipsychotics such as olanzapine, clozapine and aripiprazole. We demonstrate that the antipsychotic asenapine is also effective in treating catatonic symptoms in psychiatric disorders. CONCLUSION: Asenapine produced a rapid and significant reduction in catatonic symptoms in our patient with schizotypal personality disorder.


Subject(s)
Antipsychotic Agents/therapeutic use , COVID-19/complications , Catatonia/drug therapy , Catatonia/etiology , Depressive Disorder, Major/complications , Dibenzocycloheptenes/therapeutic use , Schizotypal Personality Disorder/complications , Shock, Septic/complications , Shock, Septic/etiology , Catatonia/psychology , Humans , Male , Middle Aged , Pain/etiology , Respiratory Distress Syndrome/complications
3.
Ann Surg ; 274(6): e829-e830, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1522435
4.
BMC Pulm Med ; 21(1): 136, 2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1511742

ABSTRACT

BACKGROUND: All over the world, SARS-CoV-2 pneumonia is causing a significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients are still unknown. METHODS: In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. At three months patients underwent radiological and functional follow-up through CT scan, lung function tests, and 6 min walking test. Furthermore, quality of life was assessed through self-reported questionnaires. RESULTS: Among 39 patients with SARS-CoV-2 pneumonia, 32 (82% of all participants) presented abnormalities in CT scan and 25 (64.1%) had lung function tests impairment at three months. Moreover, 31 patients (79.5%) reported a perception of poor health due to respiratory symptoms and all 39 patients showed an overall decreased quality of life. CONCLUSIONS: Medium-term follow up at three months of patients diagnosed with SARS-CoV-2 pneumonia shows the persistence of abnormalities in CT scans, a significant functional impairment assessed by lung function tests and a decreased quality of life in affected patients. Further studies evaluating the long-term impact are warranted to guarantee an appropriate follow-up to patients recovering from SARS-CoV-2 pneumonia.


Subject(s)
COVID-19/physiopathology , Lung/physiopathology , Quality of Life , Aged , COVID-19/diagnostic imaging , Convalescence , Female , Forced Expiratory Volume , Health Status , Humans , Length of Stay , Lung/diagnostic imaging , Male , Middle Aged , Prospective Studies , Pulmonary Diffusing Capacity , Recovery of Function , Respiratory Function Tests , SARS-CoV-2 , Switzerland , Tomography, X-Ray Computed , Vital Capacity , Walk Test
5.
J Comput Assist Tomogr ; 44(5): 627-632, 2020.
Article in English | MEDLINE | ID: covidwho-1501243

ABSTRACT

OBJECTIVE: To determine the predictive computed tomography (CT) and clinical features for diagnosis of COVID-19 pneumonia. METHODS: The CT and clinical data including were analyzed using univariate analysis and multinomial logistic regression, followed by receiver operating characteristic curve analysis. RESULTS: The factors including size of ground grass opacity (GGO), GGO with reticular and/or interlobular septal thickening, vascular enlargement, "tree-in-bud" opacity, centrilobular nodules, and stuffy or runny nose were associated with the 2 groups of viral pneumonia, as determined by univariate analysis (P < 0.05). Only GGO with reticular and/or interlobular septal thickening, centrilobular nodules, and stuffy or runny nose remained independent risk factors in multinomial logistic regression analysis. Receiver operating characteristic curve analysis showed that the area under curve of the obtained logistic regression model was 0.893. CONCLUSION: Computed tomography and clinical features including GGO with reticular and/or interlobular septal thickening, absence of centrilobular nodules, and absence of stuffy or runny nose are potential patients with COVID-19 pneumonia.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Tomography, X-Ray Computed/methods , Adult , COVID-19 , COVID-19 Testing , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pandemics , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , SARS-CoV-2
6.
Clin Infect Dis ; 73(9): e2932-e2942, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500989

ABSTRACT

BACKGROUND: Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. RESULTS: Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9-18) days for IgM and 15.0 (12-20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. CONCLUSIONS: We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.


Subject(s)
COVID-19 , Pneumonia, Viral , Antibodies, Viral , Female , Humans , Immunoglobulin M , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Seroconversion
7.
Jpn J Infect Dis ; 74(5): 458-464, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1497875

ABSTRACT

We aimed to determine the predictors of intensive care unit (ICU) admission or death in patients with coronavirus disease 2019 (COVID-19) pneumonia. This retrospective, single-center study included patients aged ≥18 years who were diagnosed with COVID-19 pneumonia (laboratory and radiologically confirmed) between March 9 and April 8, 2020. The composite endpoint was ICU admission or in-hospital mortality. Univariate and multivariate logistic regression analyses were performed to evaluate the factors associated with the composite endpoint. A total of 336 patients with COVID-19 pneumonia were evaluated. The median age was 54 years (interquartile range: 21), and 187 (55.7%) were men. Fifty-one (15.2%) patients were admitted to the ICU. In-hospital mortality occurred in 33 patients (9.8%). In the univariate analysis, 17 parameters were associated with the composite endpoint, and procalcitonin had the highest odds ratio (odds ratio [OR] = 36.568, confidence interval [CI] = 5.145-259.915). Our results revealed that body temperature (OR = 1.489, CI = 1.023-2.167, P = 0.037), peripheral capillary oxygen saturation (SpO2) (OR = 0.835, CI = 0.773-0.901, P < 0.001), and consolidation (> 25%) on chest computed tomography (OR = 3.170, CI = 1.218-8.252, P = 0.018) at admission were independent predictors. As a result, increased body temperature, decreased SpO2, a high level of procalcitonin, and degree of consolidation on chest computed tomography may predict a poor prognosis and have utility in the management of patients.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Turkey/epidemiology
8.
Crit Care Explor ; 2(9): e0194, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1493997

ABSTRACT

Objectives: Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms. Design: Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had daily blood samples collected until testing was confirmed coronavirus disease 2019 negative on either ICU day 3 or ICU day 7 if the patient was coronavirus disease 2019 positive. Interventions: None. Measurement and Main Results: Age- and sex-matched healthy control subjects and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Compared with healthy control subjects, coronavirus disease 2019 positive patients had higher plasma von Willebrand factor (p < 0.001) and glycocalyx-degradation products (chondroitin sulfate and syndecan-1; p < 0.01). When compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had persistently higher soluble P-selectin, hyaluronic acid, and syndecan-1 (p < 0.05), particularly on ICU day 3 and thereafter. Thrombosis profiling on ICU days 1-3 predicted coronavirus disease 2019 status with 85% accuracy and patient mortality with 86% accuracy. Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium. Conclusions: Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study.

9.
Crit Care Explor ; 2(9): e0189, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1493996

ABSTRACT

Objectives: Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers. Design: Blood was collected at predetermined ICU days for proximity extension assays to determine the plasma concentrations of 1,161 proteins. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient positive (coronavirus disease 2019 positive). Interventions: None. Measurements and Main Results: Age- and sex-matched healthy control subjects and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top performing proteins for identifying coronavirus disease 2019 positive ICU patients from both healthy control subjects and coronavirus disease 2019 negative ICU patients (classification accuracies 100%). The coronavirus disease 2019 proteome was dominated by interleukins and chemokines, as well as several membrane receptors linked to lymphocyte-associated microparticles and/or cell debris. Mortality was predicted for coronavirus disease 2019 positive patients based on plasma proteome profiling on both ICU day 1 (accuracy 92%) and ICU day 3 (accuracy 83%). Promising prognostic proteins were then narrowed down to six, each of which provided excellent classification performance for mortality when measured on ICU day 1 CMRF-35-like molecule, interleukin receptor-12 subunit B1, cluster of differentiation 83 [CD83], family with sequence similarity 3, insulin-like growth factor 1 receptor and opticin; area-under-the-curve =1.0; p = 0.007). Conclusions: Targeted proteomics with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 tested negative ICU patients from coronavirus disease 2019 tested positive ICU patients. Multiple proteins were identified that accurately predicted coronavirus disease 2019 tested positive patient mortality.

10.
Clin Infect Dis ; 73(2): e513-e522, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1493765

ABSTRACT

BACKGROUND: For pediatric pneumonia, the meteorological and air pollution indicators have been frequently investigated for their association with viral circulation but not for their impact on disease severity. METHODS: We performed a 10-year prospective, observational study in 1 hospital in Chongqing, China, to recruit children with pneumonia. Eight commonly seen respiratory viruses were tested. Autoregressive distributed lag (ADL) and random forest (RF) models were used to fit monthly detection rates of each virus at the population level and to predict the possibility of severe pneumonia at the individual level, respectively. RESULTS: Between 2009 and 2018, 6611 pediatric pneumonia patients were included, and 4846 (73.3%) tested positive for at least 1 respiratory virus. The patient median age was 9 months (interquartile range, 4‒20). ADL models demonstrated a decent fitting of detection rates of R2 > 0.7 for respiratory syncytial virus, human rhinovirus, parainfluenza virus, and human metapneumovirus. Based on the RF models, the area under the curve for host-related factors alone was 0.88 (95% confidence interval [CI], .87‒.89) and 0.86 (95% CI, .85‒.88) for meteorological and air pollution indicators alone and 0.62 (95% CI, .60‒.63) for viral infections alone. The final model indicated that 9 weather and air pollution indicators were important determinants of severe pneumonia, with a relative contribution of 62.53%, which is significantly higher than respiratory viral infections (7.36%). CONCLUSIONS: Meteorological and air pollution predictors contributed more to severe pneumonia in children than did respiratory viruses. These meteorological data could help predict times when children would be at increased risk for severe pneumonia and when interventions, such as reducing outdoor activities, may be warranted.


Subject(s)
Air Pollution , Pneumonia , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Virus Diseases , Air Pollution/adverse effects , Air Pollution/analysis , Child , China/epidemiology , Humans , Infant , Pneumonia/epidemiology , Pneumonia/etiology , Prospective Studies , Weather
11.
Jpn J Radiol ; 38(6): 533-538, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1479522

ABSTRACT

PURPOSE: To investigate the chest CT imaging characteristics and clinical manifestations of patients with COVID-19 pneumonia. METHODS: This study included 150 patients with COVID-19 pneumonia diagnosed from January 10 to February 12, 2020 to analyze their clinical and CT imaging characteristics. RESULTS: The period between symptom onset and initial CT examination ranged from 1 to 8 days. There were 83 cases (55.33%) involving both lungs, 67 cases (44.67%) involving a single lung (left 25 cases and right 42 cases). There were 49 cases (32.67%) of single intrapulmonary lesion, 33 cases (22.00%) of multiple intrapulmonary lesions, 68 cases (44.00%) of diffused intrapulmonary lesions, 67 cases (44.67%) of subpleural lesions, 24 cases (16.00%) of lesions localizing along the bronchovascular bundles, and 59 cases (39.33%) with lesions in both locations. There were 18 cases (12.00%) exhibiting ground-glass nodules of < 10 mm, 124 cases (82.67%) of patchy ground-glass opacities with or without consolidation, 8 cases (5.33%) of cord-like lesions, 6 cases (4.00%) of pleural effusion, and 2 cases (1.33%) of enlarged lymph nodes. CONCLUSIONS: The main manifestations of initial chest CT in COVID-19 pneumonia patients was ground-glass opacities, commonly involving single site in patients < 35 years old and multiple sites and extensive area in patients > 60 years old. The common lesion sites were the subpleural region and the posterior basal segments of the lower lobes, mostly showing thickening of the interlobular septum and mixed with consolidation.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Humans , Lung/diagnostic imaging , Middle Aged , Pandemics , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
12.
Eur Geriatr Med ; 12(5): 1045-1055, 2021 10.
Article in English | MEDLINE | ID: covidwho-1474202

ABSTRACT

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.


Subject(s)
COVID-19 , Cross Infection , Healthcare-Associated Pneumonia , Aged , Aged, 80 and over , Cross Infection/epidemiology , Female , Healthcare-Associated Pneumonia/epidemiology , Humans , Male , SARS-CoV-2 , Treatment Outcome
13.
Eur J Endocrinol ; 185(1): 137-144, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1477604

ABSTRACT

Objective: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. Design and methods: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. Results: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. Conclusions: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.


Subject(s)
COVID-19/blood , SARS-CoV-2 , Severity of Illness Index , Sodium/blood , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/mortality , Comorbidity , Critical Care/statistics & numerical data , Female , Fluorocarbons/blood , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydrocarbons, Brominated/blood , Hypernatremia/epidemiology , Hyponatremia/epidemiology , Interleukin-6/blood , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS Virus
14.
Viral Immunol ; 34(6): 416-420, 2021.
Article in English | MEDLINE | ID: covidwho-1475758

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected millions of individuals in the world. However, the long-term effect of SARS-CoV-2 on the organs of recovered patients remains unclear. This study is to evaluate the impact of SARS-CoV-2 on the spleen and T lymphocytes. Seventy-six patients recovered from COVID-19, including 66 cases of moderate pneumonia and 10 cases of severe pneumonia were enrolled in the observation group. The control group consisted of 55 age-matched healthy subjects. The thickness and length of spleen were measured by using B-ultrasound and the levels of T lymphocytes were detected by flow cytometry. Results showed that the mean length of spleen in the observation group was 89.57 ± 11.49 mm, which was significantly reduced compared with that in the control group (103.82 ± 11.29 mm, p < 0.001). The mean thicknesses of spleen between observation group and control group were 29.97 ± 4.04 mm and 32.45 ± 4.49 mm, respectively, and the difference was significant (p < 0.001). However, no significant difference was observed in the size of spleen between common pneumonia and severe pneumonia (p > 0.05). In addition, the decreased count of T lymphocyte was observed in part of recovered patients. The counts of T suppressor lymphocytes in patients with severe pneumonia were significantly decreased compared with those with moderate pneumonia (p = 0.005). Therefore, these data indicate that SARS-CoV-2 infection affects the size of spleen and T lymphocytes.


Subject(s)
COVID-19/immunology , SARS-CoV-2 , Spleen/pathology , T-Lymphocytes/immunology , Adult , Aged , Female , Humans , Lymphocyte Count , Male , Middle Aged , Young Adult
15.
J Transl Med ; 18(1): 405, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-1477432

ABSTRACT

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , Cohort Studies , Coronavirus Infections/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Mortality , Off-Label Use , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Treatment Outcome , Validation Studies as Topic
16.
Eur Respir J ; 58(3)2021 09.
Article in English | MEDLINE | ID: covidwho-1458032

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide, having a dramatic impact on healthcare systems. The aim of this study is to evaluate mid-term clinical impact of COVID-19 on respiratory function. METHODS: 379 patients were evaluated 4 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Patients were divided in two groups based on the presence of pneumonia during COVID-19. Clinical conditions, quality of life, symptomatology, 6-min walk test, pulmonary function test with spirometry and diffusing capacity of the lung for carbon monoxide were analysed. Data were compared to clinical evolution during COVID-19 (development of acute respiratory distress syndrome, need of invasive mechanical ventilation, partial oxygen saturation (S pO2 )/inspiratory oxygen fraction (F IO2 ) ratio and pneumonia severity index (PSI)). RESULTS: After a median 135 days, 260 (68.6%) out of 379 patients referred at least one symptom. Patients who developed pneumonia during COVID-19 showed lower S pO2 at rest (p<0.001), S pO2 during 6-min walk test (p<0.001), total lung capacity (p<0.001), airway occlusion pressure after 0.1 s (P 0.1) (p=0.02), P 0.1/maximal inspiratory pressure ratio (p=0.005) and higher Borg category-ratio scale (p=0.006) and modified Medical Research Council breathlessness scale (p=0.003), compared to patients without pneumonia. S pO2 /F IO2 ratio and PSI during SARS-CoV-2 pneumonia were directly associated with mid-term alteration of S pO2 at rest (p<0.001) and during 6-min walk test (p<0.001), residual volume (p<0.001), total lung capacity (p<0.001 and p=0.003, respectively) and forced vital capacity (p=0.004 and p=0.03, respectively). CONCLUSION: Lung damage during COVID-19 correlates to the reduction of pulmonary function 4 months after acute infection.


Subject(s)
COVID-19 , Quality of Life , Humans , Lung , Respiratory Function Tests , SARS-CoV-2
17.
Ghana Med J ; 54(4 Suppl): 33-38, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1436192

ABSTRACT

The study examined the clinical characteristics and outcomes of 2019 novel coronavirus disease (COVID-19) infections among hospitalized patients. Design: Study design was a retrospective single-center review of hospital data. Setting: The study was conducted at the COVID-19 Treatment Center of the Department of Medicine and Therapeutics of the Korle-Bu Teaching hospital in Accra, Ghana. Participants and study tools: A total of fifty patients with laboratory (rRT-PCR) confirmed COVID-19 infection were involved in the study. A chart review of the medical records of the patients was conducted and the data obtained was documented using a data extraction form. Results: The median age was 53 years and most (36% (18/50)) of the patients were at least 60 years of age. Eighty percent (40/50) of the patients were symptomatic, with cough and difficulty in breathing being the commonest presenting symptoms. The mean duration of hospitalization was 12.3 ± 7.3 days. Hypertension and Diabetes Mellitus were the commonest co-morbidities occurring in 52% (26/50) and 42% (21/50) of patients respectively. Fifty percent of patients developed COVID-19 pneumonia as a complication. The mortality rate was 12% (6/50). Conclusion: In this study, SARS-CoV2 infection affected older adults with hypertension and diabetes mellitus being the common comorbidities. Patients with these comorbid conditions should be counselled by their clinicians to strictly observe the COVID-19 prevention protocols to reduce their risk of acquiring the infection. There is a need to pay critical and prompt attention to the management of patients with COVID-19 pneumonia particularly among people with diabetes to improve outcomes. Funding: None declared.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , SARS-CoV-2 , COVID-19/virology , Comorbidity , Cough/epidemiology , Cough/virology , Diabetes Mellitus/epidemiology , Dyspnea/epidemiology , Dyspnea/virology , Female , Ghana/epidemiology , Hospitals, Teaching , Humans , Hypertension/epidemiology , Male , Middle Aged , Retrospective Studies
18.
J Med Virol ; 93(10): 5886-5895, 2021 10.
Article in English | MEDLINE | ID: covidwho-1432423

ABSTRACT

The clinical evolution of coronavirus disease 2019 (COVID-19) is highly variable and hospitalized patients can rapidly develop conditions requiring oxygen support, intensive care unit (ICU) or high dependency unit (HDU) care. Early identification of high-risk patients is mandatory. We retrospectively collected the medical history, symptoms, radiological, and laboratory findings of COVID-19 patients hospitalized between February and April 2020. Laboratory data were collected at the first, last, and middle times of hospitalization. We used arterial oxygen partial pressure and fractional inspired oxygen ratio (P/F) to evaluate respiratory status. Outcomes considered were death and ICU/HDU admission. We used the χ2 or Fisher's exact test to examine differences between categorical variables. Continuous variables were analyzed using the Wilcoxon matched pairs signed-ranks test and Mann-Whitney test sample test. Of 71 patients admitted, 92% had interstitial pneumonia, and 17% an unfavorable outcome. Negative predictors were age, cerebrovascular disease, obesity, and chronic obstructive pulmonary disease. Baseline P/F was strongly associated with all outcomes. Markers linked to immunological dysregulation like elevated neutrophil-to-lymphocyte ratio exhibited prognostic significance over time. A validated prognostic score comprehensive of all these conditions for early staging and management of COVID-19 patients is urgently needed. Further studies are desirable to evaluate whether laboratory tests can target early treatment in high-risk patients.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Adult , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Intensive Care Units , Italy/epidemiology , Male , Middle Aged , Patient Outcome Assessment , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2
19.
J Med Virol ; 93(10): 5789-5797, 2021 10.
Article in English | MEDLINE | ID: covidwho-1432411

ABSTRACT

There is no consensus on the management of coronavirus disease 2019 (COVID-19) and modification of immunosuppressive therapy in kidney transplant recipients (KTRs). In this study, we examined the clinical outcome of our KTRs with COVID-19 disease, who were treated with a broad-spectrum anti-inflammatory protocol. This protocol is essentially composed of intravenous immunoglobulin +/- tocilizumab in KTRs with severe COVID-19 pneumonia. Among 809 KTRs, 64 patients diagnosed with COVID-19 disease between April 2020 and February 2021, were evaluated. Twenty-nine patients with pneumonia confirmed by chest computed tomography (CCT) were hospitalized. The treatment protocol included high-dose intravenous methylprednisolone, favipiravir, enoxaparin, and empirical antibiotics. Patients with pneumonic involvement of more than 25% on CCT with or without respiratory failure were given a total of 2 g/kg intravenous immunoglobulin (IVIg) therapy. Nonresponders received tocilizumab, an interleukin-6 receptor antibody. Of the 29 patients with pneumonia, 6 were treated in other hospitals. These six patients did not receive IVIg and 5 of them deceased. In our center, IVIg treatment was applied to 15 of 23 patients. Seven of them required tocilizumab. Respiratory parameters improved significantly in all but one patient after IVIg ± tocilizumab treatment. The mortality rate was 6.6% in patients who received IVIg therapy and 35.7% in those who did not (p = 0.08). The mortality rate was higher in patients who received treatment in external centers (2.2% vs. 26.3%; p = 0.0073). The treatment of KTRs with severe COVID-19 pneumonia in organ transplant centers with significant experience yields better results. The administration of broad-spectrum anti-inflammatory treatment in this patient group was safe and provided excellent outcomes.


Subject(s)
Algorithms , COVID-19/therapy , Kidney Transplantation , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/diagnosis , COVID-19/mortality , Combined Modality Therapy , Female , Humans , Immunization, Passive/mortality , Immunoglobulins, Intravenous/therapeutic use , Immunosuppression , Lung/diagnostic imaging , Male , Middle Aged , SARS-CoV-2 , Transplant Recipients , Treatment Outcome
20.
Radiology ; 301(1): E353-E360, 2021 10.
Article in English | MEDLINE | ID: covidwho-1430241

ABSTRACT

Background SARS-CoV-2 targets angiotensin-converting enzyme 2-expressing cells in the respiratory tract. There are reports of breathlessness in patients many months after infection. Purpose To determine whether hyperpolarized xenon 129 MRI (XeMRI) imaging could be used to identify the possible cause of breathlessness in patients at 3 months after hospital discharge following COVID-19 infection. Materials and Methods This prospective study was undertaken between August and December of 2020, with patients and healthy control volunteers being enrolled. All patients underwent lung function tests; ventilation and dissolved-phase XeMRI, with the mean red blood cell (RBC) to tissue or plasma (TP) ratio being calculated; and a low-dose chest CT, with scans being scored for the degree of abnormalities after COVID-19. Healthy control volunteers underwent XeMRI. The intraclass correlation coefficient was calculated for volunteer and patient scans to assess repeatability. A Wilcoxon rank sum test and Cohen effect size calculation were performed to assess differences in the RBC/TP ratio between patients and control volunteers. Results Nine patients (mean age, 57 years ± 7 [standard deviation]; six male patients) and five volunteers (mean age, 29 years ± 3; five female volunteers) were enrolled. The mean time from hospital discharge for patients was 169 days (range, 116-254 days). There was a difference in the RBC/TP ratio between patients and control volunteers (0.3 ± 0.1 vs 0.5 ± 0.1, respectively; P = .001; effect size, 1.36). There was significant difference between the RBC and gas phase spectral full width at half maximum between volunteers and patients (median ± range, 567 ± 1 vs 507 ± 81 [P = .002] and 104 ± 2 vs 122 ± 17 [P = .004], respectively). Results were reproducible, with intraclass correlation coefficients of 0.82 and 0.88 being demonstrated for patients and volunteers, respectively. Participants had normal or nearly normal CT scans (mean, seven of 25; range, zero of 25 to 10 of 25). Conclusion Hyperpolarized xenon 129 MRI results showed alveolar capillary diffusion limitation in all nine patients after COVID-19 pneumonia, despite normal or nearly normal results at CT. © RSNA, 2021 See also the editorial by Dietrich in this issue.


Subject(s)
COVID-19/physiopathology , Dyspnea/physiopathology , Lung/diagnostic imaging , Lung/physiopathology , Magnetic Resonance Imaging/methods , Xenon Isotopes , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2
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