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The Journal of Applied Laboratory... Sep 2020Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease.
CONTENT
PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2.
SUMMARY
45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 × 109/L), platelet count (MD -22.4 × 109/L), and hemoglobin (MD, -4.1 g/L); all p < 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Diagnostic Tests, Routine; Humans; Outcome Assessment, Health Care; Pandemics; Patient Selection; Pneumonia, Viral; Reference Standards; SARS-CoV-2
PubMed: 32573713
DOI: 10.1093/jalm/jfaa098 -
Indian Journal of Pharmacology 2020Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of...
Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of "spike protein," "main protease/M Pro/3CL pro," "RNA-dependent RNA polymerase," and "nonstructural protein 15 Endoribonuclease" of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Design; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32565603
DOI: 10.4103/ijp.IJP_338_20 -
Le Infezioni in Medicina Jun 2020Coronaviruses are zoonotic viruses that include human epidemic pathogens such as the Middle East Respiratory Syndrome virus (MERS-CoV), and the Severe Acute Respiratory... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Coronaviruses are zoonotic viruses that include human epidemic pathogens such as the Middle East Respiratory Syndrome virus (MERS-CoV), and the Severe Acute Respiratory Syndrome virus (SARS-CoV), among others (e.g., COVID-19, the recently emerging coronavirus disease). The role of animals as potential reservoirs for such pathogens remains an unanswered question. No systematic reviews have been published on this topic to date.
METHODS
We performed a systematic literature review with meta-analysis, using three databases to assess MERS-CoV and SARS-CoV infection in animals and its diagnosis by serological and molecular tests. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI).
RESULTS
6,493articles were retrieved (1960-2019). After screening by abstract/title, 50 articles were selected for full-text assessment. Of them, 42 were finally included for qualitative and quantitative analyses. From a total of 34 studies (n=20,896 animals), the pool prevalence by RT-PCR for MERS-CoV was 7.2% (95%CI 5.6-8.7%), with 97.3% occurring in camels, in which pool prevalence was 10.3% (95%CI 8.3-12.3). Qatar was the country with the highest MERS-CoV RT-PCR pool prevalence: 32.6% (95%CI 4.8-60.4%). From 5 studies and 2,618 animals, for SARS-CoV, the RT-PCR pool prevalence was 2.3% (95%CI 1.3-3.3). Of those, 38.35% were reported on bats, in which the pool prevalence was 14.1% (95%CI0.0-44.6%).
DISCUSSION
A considerable proportion of infected animals tested positive, particularly by nucleic acid amplification tests (NAAT). This essential condition highlights the relevance of individual animals as reservoirs of MERS-CoV and SARS-CoV. In this meta-analysis, camels and bats were found to be positive by RT-PCR in over 10% of the cases for both; thus, suggesting their relevance in the maintenance of wild zoonotic transmission.
Topics: Animals; Animals, Domestic; Animals, Wild; Antibodies, Viral; Camelus; Chiroptera; Coronavirus Infections; Cross-Sectional Studies; Disease Reservoirs; Host Specificity; Humans; Middle East Respiratory Syndrome Coronavirus; Prevalence; Primate Diseases; Primates; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Rodent Diseases; Rodentia; Severe acute respiratory syndrome-related coronavirus; Serologic Tests; Severe Acute Respiratory Syndrome; Zoonoses
PubMed: 32532942
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Aug 2020Breast cancer is the leading cause of cancer death among women across the world. Trametes robiniophila Murr (Huaier), a traditional herbal medicine, has been used in...
Breast cancer is the leading cause of cancer death among women across the world. Trametes robiniophila Murr (Huaier), a traditional herbal medicine, has been used in China to protect human health for about 1600 years. Recent years, Huaier had been proven to be effective for multiple types of malignancies. This systematic review focused on breast cancer treatment, summarizing the curative function of Huaier aqueous extract and polysaccharides in preclinical researches. Huaier could markedly inhibit breast cancer progression with low toxicity, enhance immune response and increase the sensitivity to radiation and chemotherapy. The therapeutic effect of Huaier granule in clinical studies was also included. This review amalgamated the current studies and highlighted the promising role of Huaier and its polysaccharides as complementary alternative medicine in breast cancer treatment.
Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Complex Mixtures; Female; Fungal Polysaccharides; Humans; Polyporaceae; Trametes; Treatment Outcome
PubMed: 32480220
DOI: 10.1016/j.biopha.2020.110254 -
Stem Cells Translational Medicine Sep 2020Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with... (Meta-Analysis)
Meta-Analysis
Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO /FiO ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.
Topics: Betacoronavirus; COVID-19; Cell- and Tissue-Based Therapy; Coronavirus Infections; Cytokines; Humans; Lung; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 32472653
DOI: 10.1002/sctm.20-0146 -
Medicina Intensiva 2020On 31 December 2019, the Health Commission of Hubei Province of China first unveiled a group of unexplained cases of pneumonia, which WHO subsequently defined as the new...
On 31 December 2019, the Health Commission of Hubei Province of China first unveiled a group of unexplained cases of pneumonia, which WHO subsequently defined as the new coronavirus of 2019 (SARS-CoV-2). SARS-CoV-2 has presented rapid person-to-person transmission and is currently a global pandemic. In the largest number of cases described to date of hospitalized patients with SARS-CoV-2 disease (2019-nCoViD), 26% required care in an intensive care unit (ICU). This pandemic is causing an unprecedented mobilization of the scientific community, which has been associated with an exponentially growing number of publications in relation to it. This narrative literature review aims to gather the main contributions in the area of intensive care to date in relation to the epidemiology, clinic, diagnosis and management of 2019-nCoViD.
Topics: Age Factors; Angiotensin-Converting Enzyme 2; Antiviral Agents; Asymptomatic Infections; Betacoronavirus; COVID-19; Coronavirus Infections; Critical Care; Critical Illness; Humans; Pandemics; Peptidyl-Dipeptidase A; Personal Protective Equipment; Pneumonia, Viral; SARS-CoV-2; Standard of Care; Symptom Assessment; Triage
PubMed: 32362424
DOI: 10.1016/j.medin.2020.03.001 -
Nutrients Apr 2020For millennia, naturopaths and physicians have used (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia.... (Meta-Analysis)
Meta-Analysis Review
For millennia, naturopaths and physicians have used (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of , or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of aqueous extracts of polysaccharides and triterpenes in mice exposed to -rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of β-glucan of aqueous extract of , nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.
Topics: Animals; Drugs, Chinese Herbal; Fungal Polysaccharides; Humans; In Vitro Techniques; Mice; Phytotherapy; Radiation Injuries; Radiation-Protective Agents; Reishi; Triterpenes
PubMed: 32325828
DOI: 10.3390/nu12041143 -
BMC Infectious Diseases Apr 2020The prevalence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) is on the rise worldwide. Polymyxins are considered as last-resort drugs for CRAB... (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of polymyxins based versus non-polymyxins based therapies in the infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis.
BACKGROUND
The prevalence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) is on the rise worldwide. Polymyxins are considered as last-resort drugs for CRAB infections, but there is still controversy regarding the efficacy and safety of polymyxins based therapies in CRAB infections. The present systematic review was designed to compare the efficacy and safety of polymyxins based therapies versus non-polymyxins based therapies in CRAB infections.
METHODS
We performed a systematic literature search in PubMed, Embase, CINAHL, Cochrane Library, and clinicaltrials.gov to identify eligible studies reporting the clinical outcomes of patients with CRAB infections. The meta-analysis employed a random-effects model to estimate the odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI). The primary outcome was 1-month mortality for any cause. We also examined clinical response, microbiological response, length of stay in hospital, and adverse events.
RESULTS
Eleven eligible studies were analyzed (1052 patients in total), including 2 randomized clinical trials. Serious risk of bias was found in 8 out of the 11 studies. There was no statistically significant difference between polymyxins based therapies and non-polymyxins based therapies in 1-month mortality for any cause (OR, 0.95; 95% CI, 0.59 to 1.53), microbiological response (OR, 3.83; 95% CI, 0.90 to 16.29) and length of stay in hospital (SMD, 0.24; 95% CI, - 0.08 to 0.56). The pooled OR of clinical response indicated a significant difference in favor of polymyxin based therapies (OR, 1.99; 95% CI, 1.31 to 3.03). The pooled OR of adverse events showed that non-polymyxins based therapies were associated with fewer adverse events (OR, 4.32; 95% CI, 1.39 to 13.48).
CONCLUSION
The performance of polymyxins based therapies was better than non-polymyxin based therapies in clinical response rate and similar to non-polymyxin based therapies in terms of 1-month mortality and microbiological response in treating CRAB infections. Due to the limitations of our study, we cannot draw a firm conclusion on the optimal treatment of CRAB infections, but polymyxins would be a relatively effective treatment for CRAB infections. Adequate and well-designed large scale randomized controlled trials are required to clarify the relative efficacy of polymyxins based and non-polymyxins based therapies.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Humans; Length of Stay; Odds Ratio; Polymyxins; Treatment Outcome
PubMed: 32316926
DOI: 10.1186/s12879-020-05026-2 -
Journal For Immunotherapy of Cancer Apr 2020Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in hepatocellular carcinoma (HCC), but only a subset of patients respond to these therapies, highlighting a need for novel biomarkers to improve clinical benefit. HCC usually occurs in the setting of liver cirrhosis from chronic hepatitis B or C viral infection, but the effects of viral status on the tumor immune microenvironment and clinical responses to ICIs in HCC remains unclear.
METHODS
We conducted a meta-analysis to estimate the objective response rates for PD-1/PD-L1 inhibitors in virally-infected and uninfected patients, and examined the effects of viral etiology on the tumor microenvironment using data from The Cancer Genome Atlas, as well as peripheral blood responses using an independent cohort of patients studied by mass cytometry (cytometry by time-of-flight (CyTOF)).
RESULTS
Meta-analysis comparing objective response rates (ORR) between virally-infected and uninfected patients showed no clinically meaningful difference (absolute difference of ORR in virally-infected vs uninfected=-1.4%, 95% CI: -13.5% to 10.6%). There was no relationship between viral etiology on features of the tumor immune microenvironment that are known to modulate responses to PD-1/PD-L1 inhibitors, and the tumor mutational burden was similar between virally-infected and uninfected HCC. RNA sequencing of tissue-resident T cell and B cell repertoires similarly showed no effect of viral status on their diversity. CyTOF analysis of peripheral blood specimens further demonstrated similar expression of immune-related markers in response to PD-1 inhibitor therapy in virally-infected and uninfected HCC.
CONCLUSION
There is no significant effect of viral etiology on the tumor immune microenvironment in HCC, and viral status should not be used as a criterion to select patients for PD-1/PD-L1 therapy.
Topics: Antigens, Viral; B7-H1 Antigen; Carcinoma, Hepatocellular; Clinical Decision-Making; Hepacivirus; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Immune Checkpoint Inhibitors; Liver Neoplasms; Lymphocytes, Tumor-Infiltrating; Patient Selection; Programmed Cell Death 1 Receptor; Retrospective Studies; T-Lymphocytes; Tumor Microenvironment
PubMed: 32303615
DOI: 10.1136/jitc-2019-000394 -
Clinical Gastroenterology and... Jul 2020The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Child; Coronavirus Infections; Diarrhea; Disease Management; Disease Transmission, Infectious; Feces; Humans; Incidence; Infection Control; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Serine Endopeptidases; Spike Glycoprotein, Coronavirus; Virus Attachment; Virus Internalization
PubMed: 32278065
DOI: 10.1016/j.cgh.2020.04.001