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1.
Virus Res ; 286: 198057, 2020 09.
Article in English | MEDLINE | ID: covidwho-773200

ABSTRACT

The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drugs, Chinese Herbal/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Betacoronavirus/immunology , China/epidemiology , Chloroquine/therapeutic use , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Combinations , Humans , Indoles/therapeutic use , Interferons/therapeutic use , Lopinavir/therapeutic use , Lung/drug effects , Lung/pathology , Lung/virology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Pyrazines/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Survival Analysis
2.
Arch Pathol Lab Med ; 144(9): 1041-1047, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-771246

ABSTRACT

Since making its debut on the global stage in December 2019, coronavirus disease 2019 (COVID-19) has afflicted nearly 4 million people and caused hundreds of thousands of deaths. Case reports and case series depicting the clinical effects of the causative virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-have been published, yet few demonstrate the cytopathologic alterations of this disease. We present a clinical-pathologic correlation report of a previously healthy Hispanic woman with laboratory-confirmed COVID-19 who had typical features of acute respiratory distress syndrome (ARDS) and also showed cardiac abnormalities thought to represent fulminant viral myocarditis. Congruent with the ARDS clinical impression, autopsy findings were remarkable for extensive and markedly severe acute lung injury consistent with viral pneumonia, characterized by diffuse alveolar damage, pulmonary infarction, severe pulmonary edema, desquamation of pneumocytes with intra-alveolar aggregation, and pneumocyte morphologic alterations suggestive of viral cytopathic effect. However, there was incongruence between the clinical impression and the cardiovascular pathology findings in that viral myocarditis was not detected on histopathologic evaluation. This case highlights the importance of pathologic corroboration of the clinical impression and, in addition, illuminates the key role autopsy plays during a pandemic by providing valuable insight into viral pathology in tissues.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Lung/pathology , Mexican Americans , Myocardium/pathology , Pneumonia, Viral/pathology , Adult , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/ethnology , Coronavirus Infections/physiopathology , Fatal Outcome , Female , Heart/virology , Humans , Lung/virology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/ethnology , Pneumonia, Viral/physiopathology
3.
Trials ; 21(1): 781, 2020 Sep 11.
Article in English | MEDLINE | ID: covidwho-751154

ABSTRACT

OBJECTIVES: This study aims to demonstrate the positive effects on oxygenation of flow-controlled ventilation compared to conventionally ventilated patients in patients suffering from Acute respiratory distress syndrome (ARDS) associated with COVID-19.We define ARDS according to the "Berlin" definition integrating the oxygenation index (P/F ratio), the level of Positive End Expiratory Pressure (PEEP), radiological and clinical findings. TRIAL DESIGN: This is a prospective, randomized (1:1 ratio), parallel group feasibility study in adult patients with proven COVID-19 associated ARDS. PARTICIPANTS: All adult patients admitted to the ICU of Hamad Medical Corporation facilities in Qatar because of COVID-19 infection who develop moderate to severe ARDS are eligible. The inclusion criteria are above 18 years of age, proven COVID-19 infection, respiratory failure necessitating intubation and mechanical ventilation, ARDS with a P/F ratio of at least 200mmHg or less and a minimum PEEP 5cmH2O, BMI less 30 kg/ m2. The following exclusion criteria: no written consent, chronic respiratory disease, acute or chronic cardiovascular disease, pregnancy or need for special therapy (prone position and/or Extracorporeal membrane oxygenation). INTERVENTION AND COMPARATOR: After randomisation, the group A patients will be ventilated with the test-device for 48 hours. The settings will be started with the pre-existing-PEEP. The upper pressure will be determined to achieve a tidal volume of 6 ml/kg lean body mass, while the respiratory rate will be set to maintain an arterial pH above 7.2. In group B, the ventilator settings will be adjusted by the attending ICU team in accordance with lung-protective ventilation strategy. All other treatment will be unchanged and according to our local policies/guidelines. MAIN OUTCOMES: The primary end point is PaO2. As this is a dynamic parameter, we will record it every 6-8 hours and analyse it sequentially. RANDOMISATION: The study team screens the ventilated patients who fulfil the inclusion criteria and randomise using a 1:1 allocation ratio after consenting using a closed envelope method. The latter were prepared and sealed in advance by an independent person. BLINDING (MASKING): Due to the technical nature of the study (use of a specific ventilator) blinding is only possible for the data-analysts and the patients. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation based on the assumption of an effect size (change in PaO2) of 1.5 SDS in the primary endpoint (PaO2), an intended power of 80%, an alpha error of 5% and an equal sample ratio results in n=7 patients needed to treat. However, to compensate for dropouts we will include 10 patients in each group, which means in total 20 patients. TRIAL STATUS: The local registration number is MRC-05-018 with the protocol version number 3. The date of approval is 14th April 2020. Recruitment began 28th May 2020 and is expected to end in September 2020. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: "Flow controlled ventilation in ARDS associated with COVID-19" in ClinicalTrials.org with the registration number: NCT04399317 . Registered on 22 May 2020. FULL PROTOCOL: The full protocol 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.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/therapy , Lung/virology , Pneumonia, Viral/therapy , Respiration, Artificial , Respiratory Distress Syndrome, Adult/therapy , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Feasibility Studies , Host-Pathogen Interactions , Humans , Lung/physiopathology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Prospective Studies , Qatar , Randomized Controlled Trials as Topic , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome, Adult/diagnosis , Respiratory Distress Syndrome, Adult/physiopathology , Respiratory Distress Syndrome, Adult/virology , Time Factors , Treatment Outcome
4.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 609-612, 2020 May 28.
Article in English, Chinese | MEDLINE | ID: covidwho-745310

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a new infectious disease, which has a strong virus transmission power and complex transmission routes. This disease is prone to outbreak of cluster infection. It is difficult for medical workers to provide a better perioperative treatment for surgery patient with COVID-19 while avoiding hospital spread effectively. The perioperative management for such patients needs to fully consider the possible lung injury factors caused by anesthesia and surgery. It also needs to choose the suitable timing of the operation, carry out preoperative infection screening and evaluation, and implement lung protection strategies during and after the operation to avoid aggravating the lung injury. Meanwhile, it is necessary to pay more attention to infection prevention and control in order to avoid nosocomial infection.


Subject(s)
Coronavirus Infections/therapy , Perioperative Care , Pneumonia, Viral/therapy , Betacoronavirus , Cross Infection/prevention & control , Humans , Lung/pathology , Lung/virology , Pandemics
5.
Adv Physiol Educ ; 44(4): 545-549, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-744895

ABSTRACT

It is important to reinforce physiology and pathophysiology concepts during clinical rotations, which traditionally occur after the foundational sciences in the US medical school system. We took an opportunistic approach when the COVID-19 pandemic forced our content into virtual delivery mode, as clinical medical education required a shift to nonpatient contact. We describe our experience in building a 2-wk course that consisted of online small groups during week 1 and panels and cases during week 2. The physiology content involved faculty-vetted resources, along with both discrete and open-ended focus questions for each learning objective. The course also included mechanical ventilation, and the physiologist utilized discussion points and developed a formative quiz to emphasize the physiology correlates, in addition to the very clinical aspects of mechanical ventilation. There were pathophysiology opportunities with pneumonia, acute respiratory distress syndrome, systemic inflammatory response syndrome, and multiple-organ system dysfunction among the clinical correlates. Review and recall of the foundational sciences occurred, allowing links between the pre-clerkship and clerkship years that were previously undiscovered in our institution. This virtually delivered medical curriculum related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 is timely, carries high student interest, and can benefit medical students and the communities they serve.


Subject(s)
Betacoronavirus/pathogenicity , Computer-Assisted Instruction , Coronavirus Infections/physiopathology , Education, Distance , Education, Medical, Undergraduate , Lung/physiopathology , Physiology/education , Pneumonia, Viral/physiopathology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Coronavirus Infections/virology , Host Microbial Interactions , Humans , Lung/virology , Pandemics , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Schools, Medical
6.
Signal Transduct Target Ther ; 5(1): 186, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-744366

ABSTRACT

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients' blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.


Subject(s)
Betacoronavirus/pathogenicity , Cholesterol/biosynthesis , Coronavirus Infections/genetics , Cytokine Release Syndrome/genetics , Host-Pathogen Interactions/genetics , Leukocytes, Mononuclear/immunology , Pneumonia, Viral/genetics , Sterol Regulatory Element Binding Protein 2/genetics , Betacoronavirus/immunology , Case-Control Studies , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Gene Expression Regulation , Heat-Shock Proteins/genetics , Heat-Shock Proteins/immunology , Host-Pathogen Interactions/immunology , Humans , Intensive Care Units , Interleukin-1beta/genetics , Interleukin-1beta/immunology , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/virology , Lung/immunology , Lung/metabolism , Lung/virology , NF-kappa B/genetics , NF-kappa B/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Primary Cell Culture , Proprotein Convertase 9/genetics , Proprotein Convertase 9/immunology , Signal Transduction , Sterol Regulatory Element Binding Protein 2/immunology , Survival Analysis , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
7.
Int J Mol Sci ; 21(17)2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740495

ABSTRACT

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.


Subject(s)
Apoptosis/drug effects , Betacoronavirus/physiology , Cannabinoid Receptor Agonists/therapeutic use , Coronavirus Infections/drug therapy , Cytokines/immunology , Dronabinol/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome, Adult/drug therapy , Aged , Animals , Bronchoalveolar Lavage Fluid/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Enterotoxins/adverse effects , Female , Humans , Lung/immunology , Lung/virology , Male , Mice , Mice, Inbred C3H , MicroRNAs/genetics , Middle Aged , Pandemics , Pneumonia/drug therapy , Pneumonia/virology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Respiratory Distress Syndrome, Adult/mortality , Respiratory Distress Syndrome, Adult/virology , Signal Transduction/drug effects
8.
Medicine (Baltimore) ; 99(33): e21581, 2020 Aug 14.
Article in English | MEDLINE | ID: covidwho-740195

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has caused an international outbreak of a respiratory illness and grown to be a global public health emergency since patients were first detected in Wuhan, China. Given the rapidly growing pandemic and the overwhelmed medical system, there is an urgent need of alternative medicine to help children relieve symptoms during self-quarantine, and possibly to help increase their chances of survival and recovery from COVID-19. By using various manual techniques at specified locations on the surface of the body, pediatric massage manipulation can unblock meridians, promote the circulation of qi and blood and strengthen resistance to pathogens. METHODS: We will search the following electronic databases: Wanfang and Pubmed Database, CNKI, CENTRAL, CINAHL, EMBASE and MEDLINE. Each database will be searched from inception to June 2020. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses. RESULTS: This systematic review will evaluate the existing evidence of pediatric massage therapy for restoring pediatric lung function from COVID-19. The outcomes will include the improvement of pulmonary function and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence and explore the potential role of pediatric massage therapy on the effectiveness and safety in pulmonary function of COVID-19 convalescent children. PROSPERO REGISTRATION NUMBER: CRD42020193396.


Subject(s)
Betacoronavirus , Coronavirus Infections/rehabilitation , Massage/methods , Pneumonia, Viral/rehabilitation , Child , Coronavirus Infections/physiopathology , Female , Humans , Lung/physiopathology , Lung/virology , Male , Meta-Analysis as Topic , Pandemics , Pneumonia, Viral/physiopathology , Research Design , Systematic Reviews as Topic , Treatment Outcome
10.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-725886

ABSTRACT

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


Subject(s)
Bacteremia/pathology , Bacterial Infections/pathology , Coronavirus Infections/pathology , Fungemia/pathology , Mycoses/pathology , Opportunistic Infections/pathology , Pneumonia, Viral/pathology , Respiratory Tract Infections/pathology , Urinary Tract Infections/pathology , Aged , Bacteremia/microbiology , Bacteremia/mortality , Bacteremia/virology , Bacterial Infections/microbiology , Bacterial Infections/mortality , Bacterial Infections/virology , Betacoronavirus/pathogenicity , Coronavirus Infections/microbiology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Critical Illness , Female , Fungemia/microbiology , Fungemia/mortality , Fungemia/virology , Fungi/pathogenicity , Gram-Negative Bacteria/pathogenicity , Gram-Positive Bacteria/pathogenicity , Humans , Intensive Care Units , Lung/microbiology , Lung/pathology , Lung/virology , Male , Middle Aged , Mycoses/microbiology , Mycoses/mortality , Mycoses/virology , Opportunistic Infections/microbiology , Opportunistic Infections/mortality , Opportunistic Infections/virology , Pandemics , Pneumonia, Viral/microbiology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Respiration, Artificial/adverse effects , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Respiratory Tract Infections/virology , Retrospective Studies , Risk , Severity of Illness Index , Survival Analysis , Urinary Tract Infections/microbiology , Urinary Tract Infections/mortality , Urinary Tract Infections/virology
11.
Signal Transduct Target Ther ; 5(1): 157, 2020 10 19.
Article in English | MEDLINE | ID: covidwho-724972

ABSTRACT

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Callithrix/virology , Coronavirus Infections/epidemiology , Disease Models, Animal , Macaca fascicularis/virology , Macaca mulatta/virology , Pandemics , Pneumonia, Viral/epidemiology , Animals , Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , Body Temperature , Body Weight , Callithrix/immunology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokines/biosynthesis , Cytokines/classification , Cytokines/immunology , Disease Susceptibility , Female , Humans , Lung/diagnostic imaging , Lung/immunology , Lung/pathology , Lung/virology , Macaca fascicularis/immunology , Macaca mulatta/immunology , Male , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Species Specificity , Tomography, X-Ray Computed , Viral Load , Virus Replication
12.
Elife ; 92020 08 20.
Article in English | MEDLINE | ID: covidwho-724355

ABSTRACT

We present a three-dimensional (3D) approach for virtual histology and histopathology based on multi-scale phase contrast x-ray tomography, and use this to investigate the parenchymal architecture of unstained lung tissue from patients who succumbed to Covid-19. Based on this first proof-of-concept study, we propose multi-scale phase contrast x-ray tomography as a tool to unravel the pathophysiology of Covid-19, extending conventional histology by a third dimension and allowing for full quantification of tissue remodeling. By combining parallel and cone beam geometry, autopsy samples with a maximum cross section of 8 mm are scanned and reconstructed at a resolution and image quality, which allows for the segmentation of individual cells. Using the zoom capability of the cone beam geometry, regions-of-interest are reconstructed with a minimum voxel size of 167 nm. We exemplify the capability of this approach by 3D visualization of diffuse alveolar damage (DAD) with its prominent hyaline membrane formation, by mapping the 3D distribution and density of lymphocytes infiltrating the tissue, and by providing histograms of characteristic distances from tissue interior to the closest air compartment.


Subject(s)
Betacoronavirus/pathogenicity , Clinical Laboratory Techniques , Coronavirus Infections/diagnostic imaging , Imaging, Three-Dimensional , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Autopsy , Biopsy , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Host Microbial Interactions , Humans , Lung/pathology , Lung/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Predictive Value of Tests , Proof of Concept Study , Young Adult
13.
Appl Microbiol Biotechnol ; 104(19): 8089-8104, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-723331

ABSTRACT

Interspecies transmissions of viruses between animals and humans may result in unpredictable pathogenic potential and new transmissible diseases. This mechanism has recently been exemplified by the discovery of new pathogenic viruses, such as the novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic, Middle-East respiratory syndrome-coronavirus epidemic in Saudi Arabia, and the deadly outbreak of Ebola in West Africa. The. SARS-CoV-2 causes coronavirus disease-19 (COVID-19), which is having a massive global impact in terms of economic disruption, and, above all, human health. The disease is characterized by dry cough, fever, fatigue, myalgia, and dyspnea. Other symptoms include headache, sore throat, rhinorrhea, and gastrointestinal disorders. Pneumonia appears to be the most common and severe manifestation of the infection. Currently, there is no vaccine or specific drug for COVID-19. Further, the development of new antiviral requires a considerable length of time and effort for drug design and validation. Therefore, repurposing the use of natural compounds can provide alternatives and can support therapy against COVID-19. In this review, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics for the management of COVID-19. In addition, the unique role of probiotics to modulate the gut microbe and assert gut homeostasis and production of interferon as an antiviral mechanism is described. Further, the regulatory role of probiotics on gut-lung axis and mucosal immune system for the potential antiviral mechanisms is reviewed and discussed.Key points• Gut microbiota role in antiviral diseases• Factors influencing the antiviral mechanism• Probiotics and Covid-19.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Probiotics/therapeutic use , Animals , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Gastrointestinal Tract/microbiology , Humans , Immunity, Mucosal , Lung/immunology , Lung/microbiology , Lung/virology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Probiotics/metabolism , Respiratory Tract Infections/microbiology , Virus Diseases/prevention & control , Virus Diseases/therapy , Virus Diseases/transmission , Vitamin D/physiology , Zinc/metabolism
16.
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
18.
Crit Care ; 24(1): 495, 2020 08 12.
Article in English | MEDLINE | ID: covidwho-714111

ABSTRACT

BACKGROUND: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. METHODS: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. RESULTS: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). CONCLUSIONS: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Aged , Autopsy , Brain/virology , Colon/virology , Coronavirus Infections/therapy , Female , Heart/virology , Humans , Kidney/virology , Liver/virology , Lung/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Reverse Transcriptase Polymerase Chain Reaction , Spleen/virology
19.
Am J Physiol Cell Physiol ; 319(2): C244-C249, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-711625

ABSTRACT

The outbreak of COVID-19 pneumonia caused by a new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) is posing a global health emergency and has led to more than 380,000 deaths worldwide. The cell entry of SARS-CoV-2 depends on two host proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). There is currently no vaccine available and also no effective drug for the treatment of COVID-19. Hydrogen sulfide (H2S) as a novel gasotransmitter has been shown to protect against lung damage via its anti-inflammation, antioxidative stress, antiviral, prosurvival, and antiaging effects. In light of the research advances on H2S signaling in biology and medicine, this review proposed H2S as a potential defense against COVID-19. It is suggested that H2S may block SARS-CoV-2 entry into host cells by interfering with ACE2 and TMPRSS2, inhibit SARS-CoV-2 replication by attenuating virus assembly/release, and protect SARS-CoV-2-induced lung damage by suppressing immune response and inflammation development. Preclinical studies and clinical trials with slow-releasing H2S donor(s) or the activators of endogenous H2S-generating enzymes should be considered as a preventative treatment or therapy for COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Hydrogen Sulfide/therapeutic use , Pneumonia, Viral/drug therapy , Virus Internalization/drug effects , Virus Replication/drug effects , Animals , Betacoronavirus/pathogenicity , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Hydrogen Sulfide/metabolism , Lung/drug effects , Lung/metabolism , Lung/virology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Serine Endopeptidases/metabolism , Signal Transduction
20.
Cell Host Microbe ; 28(3): 465-474.e4, 2020 09 09.
Article in English | MEDLINE | ID: covidwho-710174

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vesicular stomatitis Indiana virus/genetics , Viral Vaccines/genetics , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Chlorocebus aethiops , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Disease Models, Animal , Genetic Vectors , Green Fluorescent Proteins/genetics , Host Microbial Interactions/immunology , Humans , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Transgenic , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Receptors, Virus/genetics , Translational Medical Research , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Vaccines, Synthetic/pharmacology , Vero Cells , Vesicular stomatitis Indiana virus/immunology , Viral Vaccines/immunology , Viral Vaccines/pharmacology
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