Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 342
Filter
Add filters

Document Type
Year range
1.
Aging (Albany NY) ; 13(21): 23895-23912, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1498164

ABSTRACT

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1ß, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.


Subject(s)
COVID-19 , Critical Illness , Interleukins/blood , Pneumonia, Viral , Tumor Necrosis Factor-alpha/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , China/epidemiology , Critical Illness/mortality , Critical Illness/therapy , Female , Hospital Mortality , Humans , Immunologic Tests/methods , Male , Middle Aged , Mortality , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/etiology , Predictive Value of Tests , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed/methods , Tumor Necrosis Factor Inhibitors/therapeutic use
4.
Viruses ; 13(9)2021 08 30.
Article in English | MEDLINE | ID: covidwho-1390784

ABSTRACT

Respiratory tract infections constitute a significant public health problem, with a therapeutic arsenal that remains relatively limited and that is threatened by the emergence of antiviral and/or antibiotic resistance. Viral-bacterial co-infections are very often associated with the severity of these respiratory infections and have been explored mainly in the context of bacterial superinfections following primary influenza infection. This review summarizes our current knowledge of the mechanisms underlying these co-infections between respiratory viruses (influenza viruses, RSV, and SARS-CoV-2) and bacteria, at both the physiological and immunological levels. This review also explores the importance of the microbiome and the pathological context in the evolution of these respiratory tract co-infections and presents the different in vitro and in vivo experimental models available. A better understanding of the complex functional interactions between viruses/bacteria and host cells will allow the development of new, specific, and more effective diagnostic and therapeutic approaches.


Subject(s)
Coinfection , Pneumonia, Bacterial/epidemiology , Pneumonia, Viral/epidemiology , Disease Management , Disease Susceptibility , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate , Microbiota , Pneumonia, Bacterial/etiology , Pneumonia, Viral/etiology , Superinfection
7.
BMC Pregnancy Childbirth ; 21(1): 587, 2021 Aug 26.
Article in English | MEDLINE | ID: covidwho-1371956

ABSTRACT

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited. CASE PRESENTATION: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28+ 1 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient. CONCLUSIONS: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.


Subject(s)
COVID-19 , Cesarean Section/methods , Pneumonia, Viral , Pregnancy Complications, Infectious , Premature Birth , Respiratory Distress Syndrome , SARS-CoV-2/isolation & purification , Adult , COVID-19/complications , COVID-19/diagnosis , Female , Fetal Monitoring/methods , Gestational Age , Humans , Obesity, Morbid/diagnosis , Obesity, Morbid/physiopathology , Patient Care Team/organization & administration , Perinatal Care/methods , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/etiology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Premature Birth/etiology , Premature Birth/therapy , Respiration, Artificial/methods , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Treatment Outcome
8.
Adv Genet ; 106: 75-100, 2020.
Article in English | MEDLINE | ID: covidwho-1363831

ABSTRACT

The origins and global spread of two recent, yet quite different, pandemic diseases is discussed and reviewed in depth: Candida auris, a eukaryotic fungal disease, and COVID-19 (SARS-CoV-2), a positive strand RNA viral respiratory disease. Both these diseases display highly distinctive patterns of sudden emergence and global spread, which are not easy to understand by conventional epidemiological analysis based on simple infection-driven human- to-human spread of an infectious disease (assumed to jump suddenly and thus genetically, from an animal reservoir). Both these enigmatic diseases make sense however under a Panspermia in-fall model and the evidence consistent with such a model is critically reviewed.


Subject(s)
Biological Evolution , Candidiasis/etiology , Communicable Diseases, Emerging/etiology , Coronavirus Infections/etiology , Origin of Life , Pneumonia, Viral/etiology , Animals , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Candida/isolation & purification , Candida/physiology , Candidiasis/epidemiology , Communicable Diseases, Emerging/epidemiology , Coronavirus/isolation & purification , Coronavirus/physiology , Coronavirus Infections/epidemiology , Earth, Planet , Exobiology , Extraterrestrial Environment , Host-Pathogen Interactions/physiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
9.
BMC Pulm Med ; 21(1): 267, 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1362053

ABSTRACT

BACKGROUND: The aim of the study is to estimate the prevalence of atelectasis assessed with computer tomography (CT) in SARS-CoV-2 pneumonia and the relationship between the amount of atelectasis with oxygenation impairment, Intensive Care Unit admission rate and the length of in-hospital stay. PATIENTS AND METHODS: Two-hundred thirty-seven patients admitted to the hospital with SARS-CoV-2 pneumonia diagnosed by clinical, radiology and molecular tests in the nasopharyngeal swab who underwent a chest computed tomography because of a respiratory worsening from Apr 1 to Apr 30, 2020 were included in the study. Patients were divided into three groups depending on the presence and amount of atelectasis at the computed tomography: no atelectasis, small atelectasis (< 5% of the estimated lung volume) or large atelectasis (> 5% of the estimated lung volume). In all patients, clinical severity, oxygen-therapy need, Intensive Care Unit admission rate, the length of in-hospital stay and in-hospital mortality data were collected. RESULTS: Thirty patients (19%) showed small atelectasis while eight patients (5%) showed large atelectasis. One hundred and seventeen patients (76%) did not show atelectasis. Patients with large atelectasis compared to patients with small atelectasis had lower SatO2/FiO2 (182 vs 411 respectively, p = 0.01), needed more days of oxygen therapy (20 vs 5 days respectively, p = 0,02), more frequently Intensive Care Unit admission (75% vs 7% respectively, p < 0.01) and a longer period of hospitalization (40 vs 14 days respectively p < 0.01). CONCLUSION: In patients with SARS-CoV-2 pneumonia, atelectasis might appear in up to 24% of patients and the presence of larger amount of atelectasis is associated with worse oxygenation and clinical outcome.


Subject(s)
COVID-19 , Hypoxia , Pneumonia, Viral , Pulmonary Atelectasis , Tomography, X-Ray Computed/methods , Aged , COVID-19/diagnosis , COVID-19/mortality , COVID-19/physiopathology , COVID-19 Testing/methods , Female , Humans , Hypoxia/etiology , Hypoxia/therapy , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Lung Volume Measurements/methods , Male , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Prevalence , Pulmonary Atelectasis/diagnostic imaging , Pulmonary Atelectasis/epidemiology , Pulmonary Atelectasis/etiology , Pulmonary Atelectasis/physiopathology , Respiration, Artificial/methods , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spain/epidemiology , Tomography, X-Ray Computed/statistics & numerical data
10.
Microb Biotechnol ; 13(5): 1289-1299, 2020 09.
Article in English | MEDLINE | ID: covidwho-1352399

ABSTRACT

The number of people infected with SARS-CoV-2, and sadly dying from COVID-19, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision-making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini-review is an update of earlier reports (Brüssow, Microb Biotechnol 2020a;13:607; Brüssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592).


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/etiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Clinical Trials as Topic , Disease Models, Animal , Humans , Pandemics , Peptidyl-Dipeptidase A/physiology , RNA, Viral/analysis , SARS-CoV-2 , Viral Tropism
11.
Medicine (Baltimore) ; 100(29): e26533, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1331614

ABSTRACT

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Intensive Care Units/statistics & numerical data , Interleukin-6/antagonists & inhibitors , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Female , Humans , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Prognosis , Retrospective Studies
12.
J Clin Invest ; 131(14)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1311200

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.


Subject(s)
COVID-19/etiology , Pneumonia, Viral/etiology , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/physiology , Autopsy , COVID-19/epidemiology , COVID-19/pathology , Cytokines/biosynthesis , Humans , Lung/immunology , Lung/pathology , Lung/virology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/virology , Models, Biological , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Receptors, Virus/physiology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Severity of Illness Index
13.
Pharmacol Res ; 159: 104946, 2020 09.
Article in English | MEDLINE | ID: covidwho-1279674

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Pandemics , Pneumonia, Viral/blood , Biomarkers/blood , COVID-19 , Coronavirus Infections/etiology , Coronavirus Infections/immunology , Cytokines/blood , Disease Progression , Humans , Interleukin-10/blood , Interleukin-6/blood , Lymphopenia/etiology , Lymphopenia/immunology , Pneumonia, Viral/etiology , Pneumonia, Viral/immunology , Procalcitonin/blood , SARS-CoV-2
14.
Respir Med ; 186: 106516, 2021 09.
Article in English | MEDLINE | ID: covidwho-1275693

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through respiratory droplets, aerosols and close contact. Cross infections occur because viruses spread rapidly among humans. Nineteen percent (19%) of the infected patients developed severe pneumonia and acute respiratory distress syndrome (ARDS). Hypoxemia usually occurs and patients may require oxygen therapy or mechanical ventilation (MV) support. In this article, recently published clinical experience and observational studies were reviewed. Corresponding respiratory therapy regarding different stages of infection is proposed. Infection control principles and respiratory strategies including oxygen therapy, non-invasive respiratory support (NIRS), intubation evaluation, equipment preparation, ventilator settings, special maneuvers comprise of the prone position (PP), recruitment maneuver (RM), extracorporeal membrane oxygenation (ECMO), weaning and extubation are summarized. Respiratory equipment and device disinfection recommendations are worked up. We expect this review article could be used as a reference by healthcare workers in patient care while minimizing the risk of environmental contamination.


Subject(s)
COVID-19/prevention & control , COVID-19/therapy , Critical Care/methods , Critical Illness , Extracorporeal Membrane Oxygenation/methods , Infection Control/methods , Oxygen Inhalation Therapy/methods , Respiration, Artificial/methods , SARS-CoV-2/pathogenicity , COVID-19/complications , COVID-19/transmission , Cannula , Cross Infection/prevention & control , Cross Infection/transmission , Cross Infection/virology , Humans , Hypoxia/etiology , Hypoxia/therapy , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy
15.
Clin Transl Gastroenterol ; 12(6): e00348, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1259760

ABSTRACT

INTRODUCTION: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications. METHODS: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered. RESULTS: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events. DISCUSSION: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.


Subject(s)
COVID-19 , Endotoxemia , Haptoglobins/metabolism , Intestinal Mucosa , Protein Precursors/metabolism , SARS-CoV-2 , Thrombosis , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , Correlation of Data , Endotoxemia/diagnosis , Endotoxemia/metabolism , Endotoxemia/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/virology , Lipopolysaccharides/analysis , Male , Middle Aged , Permeability , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology
16.
Pan Afr Med J ; 38: 273, 2021.
Article in English | MEDLINE | ID: covidwho-1248412

ABSTRACT

Coronavirus 2019 disease (COVID-19) is a deadly disease that was first seen in Wuhan, China, and primarily affects the respiratory system, but also has different systemic involvements. It has caused 89 million cases and 1.9 million deaths worldwide. COVID-19 positive renal transplant recipients have a higher mortality rate than COVID-19 patients in the normal population. There is no specific treatment and follow-up protocol for COVID-19 infection in transplant recipients. COVID-19 treatment and immunosuppressive therapy choices are controversial. Recently, pulse steroid therapies have been used in cases with severe COVID-19 pneumonia. Convalescent plasma therapy is used limitedly in COVID-19 patients. Our 49-year-old male patient has been a recipient of a renal transplant from a cadaver for 6 years. We aimed to make an additional contribution by presenting our patient to the literature whose COVID-19 PCR-RT test performed in the emergency department due to the complaints of fever, shortness of breath, and cough for five days was positive and had moderate COVID-19 pneumonia in thorax tomography and had serious clinical and radiological improvement after pulsed methylprednisolone and convalescent plasma therapy in the early period.


Subject(s)
COVID-19/therapy , Methylprednisolone/administration & dosage , Pneumonia, Viral/therapy , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , Combined Modality Therapy , Glucocorticoids/administration & dosage , Humans , Immunization, Passive , Kidney Transplantation , Male , Middle Aged , Pneumonia, Viral/etiology , Pulse Therapy, Drug , Transplant Recipients , Treatment Outcome
17.
JAMA Netw Open ; 4(5): e218828, 2021 05 03.
Article in English | MEDLINE | ID: covidwho-1210568

ABSTRACT

Importance: In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted. Objective: To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics. Design, Setting, and Participants: This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site. Main Outcomes and Measures: In-hospital death adjusted for exposures for 4 periods in 2020. Results: The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73). Conclusions and Relevance: In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.


Subject(s)
COVID-19 , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Pneumonia, Viral/diagnostic imaging , Time Factors , Age Factors , COVID-19/mortality , COVID-19/therapy , Cohort Studies , Female , Humans , Male , Middle Aged , Patient Outcome Assessment , Pneumonia, Viral/etiology , Registries , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , United States/epidemiology , Vital Signs
18.
Immunity ; 54(6): 1186-1199.e7, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1207036

ABSTRACT

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus. Mechanistically, Notch4 suppressed the induction by interleukin-18 of amphiregulin, a cytokine necessary for tissue repair. Protection by Notch4 inhibition was recapitulated by therapy with Amphiregulin and, reciprocally, abrogated by its antagonism. Amphiregulin declined in COVID-19 subjects as a function of disease severity and Notch4 expression. Thus, Notch4 expression on Treg cells dynamically restrains amphiregulin-dependent tissue repair to promote severe lung inflammation, with therapeutic implications for COVID-19 and related infections.


Subject(s)
Host-Pathogen Interactions , Immunity, Cellular , Pneumonia, Viral/etiology , Pneumonia, Viral/metabolism , Receptor, Notch4/metabolism , Signal Transduction , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Amphiregulin/pharmacology , Animals , Biomarkers , Cytokines/metabolism , Disease Models, Animal , Disease Susceptibility , Host-Pathogen Interactions/immunology , Humans , Immunohistochemistry , Immunomodulation/drug effects , Inflammation Mediators/metabolism , Influenza A virus/physiology , Lung/immunology , Lung/metabolism , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Pneumonia, Viral/pathology , Receptor, Notch4/antagonists & inhibitors , Receptor, Notch4/genetics , Severity of Illness Index
19.
mBio ; 12(2)2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195827

ABSTRACT

Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has caused extensive mortality and morbidity and wreaked havoc on socioeconomic structures. The urgent need to better understand SARS-CoV-2 biology and enable continued development of effective countermeasures is aided by the production of laboratory tools that facilitate SARS-CoV-2 research. We previously created a directly accessible SARS-CoV-2 toolkit containing user-friendly reverse genetic (RG) infectious clones of SARS-CoV-2. Here, using K18-human ACE2 (hACE2) mice, we confirmed the validity of RG-rescued SARS-CoV-2 viruses to reproduce the infection profile, clinical disease, and pathogenesis already established in mice infected with natural SARS-CoV-2 isolates, often patient derived. RG-rescued SARS-CoV-2-infected K18-hACE2 mice developed substantial clinical disease and weight loss by day 6 postinfection. RG-rescued SARS-CoV-2 was recovered from the lungs and brains of infected K18-hACE2 mice, and infection resulted in viral pneumonia with considerable changes in lung pathology, as seen previously with natural SARS-CoV-2 infection. In mice infected with RG-rescued SARS-CoV-2-mCherry, mCherry was detected in areas of lung consolidation and colocalized with clinically relevant SARS-CoV-2-assocated immunopathology. RG-rescued SARS-CoV-2 viruses successfully recapitulated many of the features of severe COVID-19 associated with the K18-hACE2 model of SARS-CoV-2 infection. With utility in vivo, the RG-rescued SARS-CoV-2 viruses will be valuable resources to advance numerous areas of SARS-CoV-2 basic research and COVID-19 vaccine development.IMPORTANCE To develop COVID-19 countermeasures, powerful research tools are essential. We produced a SARS-COV-2 reverse genetic (RG) infectious clone toolkit that will benefit a variety of investigations. In this study, we further prove the toolkit's value by demonstrating the in vivo utility of RG-rescued SARS-CoV-2 isolates. RG-rescued SARS-CoV-2 isolates reproduce disease signs and pathology characteristic of the K18-hACE2 mouse model of severe COVID-19 in infected mice. Having been validated as a model of severe COVID-19 previously using only natural SARS-CoV-2 isolated from patients, this is the first investigation of RG-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The RG-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/etiology , SARS-CoV-2/pathogenicity , Animals , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/etiology , Disease Models, Animal , Female , Host Microbial Interactions , Humans , Inflammation Mediators/metabolism , Lung/immunology , Lung/pathology , Lung/virology , Male , Mice , Mice, Transgenic , Pandemics , Pneumonia, Viral/etiology , Pneumonia, Viral/virology , Reverse Genetics/methods , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Viral Tropism , Virus Replication
20.
J Vasc Surg Venous Lymphat Disord ; 9(3): 592-596, 2021 05.
Article in English | MEDLINE | ID: covidwho-1193413

ABSTRACT

BACKGROUND: Venous thromboembolic events have been one of the main causes of mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia. The aim of our study was to describe the prevalence of deep vein thrombosis (DVT) in noncritically ill patients with COVID-19 pneumonia and correlate such observations with the thromboprophylaxis received. METHODS: We performed a prospective cohort study of 67 patients admitted to the hospital for COVID-19 pneumonia. The diagnosis was confirmed using polymerase chain reaction testing of nasopharyngeal specimens. The deep veins were examined using compression duplex ultrasonography with the transducer on B-mode. The patients were separated into two groups for statistical analysis: those receiving low-molecular-weight heparin prophylaxis and those receiving intermediate or complete anticoagulation treatment. Risk analysis and logistic regression were performed. RESULTS: Of the 67 patients, 57 were included in the present study after applying the inclusion and exclusion criteria; 49.1% were women, and the patient mean age was 71.3 years. All 57 patients had undergone compression duplex ultrasonography. Of these 57 patients, 6 were diagnosed with DVT, for an in-hospital rate of DVT in patients with COVID-19 pneumonia of 10.5%. All the patients who had presented with DVT had been receiving low-molecular-weight heparin prophylaxis. The patients receiving prophylactic anticoagulation treatment had a greater risk of DVT (16.21%; 95% confidence interval, 0.04-0.28; P = .056) compared with those receiving intermediate or complete anticoagulation treatment. We also found a protective factor for DVT in the intermediate or complete anticoagulation treatment group (odds ratio, 0.19; 95% confidence interval, 0.08-0.46; P < .05). CONCLUSIONS: Noncritically ill, hospitalized patients with COVID-19 pneumonia have a high risk of DVT despite receipt of correct, standard thromboprophylaxis.


Subject(s)
Anticoagulants/administration & dosage , COVID-19 , Patients' Rooms/statistics & numerical data , Pneumonia, Viral , Venous Thrombosis , Aged , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Chemoprevention/methods , Chemoprevention/statistics & numerical data , Cohort Studies , Female , Heparin, Low-Molecular-Weight , Hospitalization/statistics & numerical data , Humans , Male , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , Prevalence , Risk Assessment , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spain/epidemiology , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
SELECTION OF CITATIONS
SEARCH DETAIL
...