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Reviews in Medical Virology May 2021A key consideration in the Covid-19 pandemic is the dominant modes of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The...
A key consideration in the Covid-19 pandemic is the dominant modes of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The objective of this review was to synthesise the evidence for the potential airborne transmission of SARS-CoV-2 via aerosols. Systematic literature searches were conducted in PubMed, Embase, Europe PMC and National Health Service UK evidence up to 27 July 2020. A protocol was published and Cochrane guidance for rapid review methodology was adhered to throughout. Twenty-eight studies were identified. Seven out of eight epidemiological studies suggest aerosol transmission may occur, with enclosed environments and poor ventilation noted as possible contextual factors. Ten of the 16 air sampling studies detected SARS-CoV-2 ribonucleic acid; however, only three of these studies attempted to culture the virus with one being successful in a limited number of samples. Two of four virological studies using artificially generated aerosols indicated that SARS-CoV-2 is viable in aerosols. The results of this review indicate there is inconclusive evidence regarding the viability and infectivity of SARS-CoV-2 in aerosols. Epidemiological studies suggest possible transmission, with contextual factors noted. Viral particles have been detected in air sampling studies with some evidence of clinical infectivity, and virological studies indicate these particles may represent live virus, adding further plausibility. However, there is uncertainty as to the nature and impact of aerosol transmission of SARS-CoV-2, and its relative contribution to the Covid-19 pandemic compared with other modes of transmission.
Topics: Aerosols; COVID-19; Humans; RNA, Viral; Retrospective Studies; SARS-CoV-2; Uncertainty
PubMed: 33105071
DOI: 10.1002/rmv.2184 -
Pathogens (Basel, Switzerland) Feb 2021Animal intestines are the source of edible sausage casings, which are traded worldwide and may come from areas where notifiable infectious animal diseases are prevalent....
Animal intestines are the source of edible sausage casings, which are traded worldwide and may come from areas where notifiable infectious animal diseases are prevalent. To estimate the risks of virus contamination, knowledge about the quantity of virus and decimal reduction values of the standard preservation method by salting is of great importance. A literature search, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed in search engine CAB Abstracts to determine the viral load of 14 relevant animal viruses in natural casings or intestines. Only a very limited number of scientific publications per virus were found and viral loads in the intestines varied from high for ASFV (five publications), BVDV (3), CSFV (6), PPRV (3), RPV(2) and TGEV (3) to moderate for PEDV (2) and SVDV (3), low for HEV (2) and FMDV (5), very low for VESV (1) and negative for PrV (2) and VSV (1). PRRSV was found in intestines, however, viral titers were not published. Three viruses (BVDV, CSFV and PPRV) with high viral loads were selected to search for their inactivation kinetics. For casings, no inactivation data were found, however, thermal inactivation data of these viruses were available, but differed in quantity, quality and matrices. In conclusion, important data gaps still exist when it comes to the quantitative inactivation of viruses in sausage casings or livestock intestines.
PubMed: 33557372
DOI: 10.3390/pathogens10020173 -
The British Journal of Radiology Mar 2021To perform a systematic review and meta-analysis to compare the diagnostic accuracy of CT and initial reverse transcriptase polymerase chain reaction (RT-PCR) for... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To perform a systematic review and meta-analysis to compare the diagnostic accuracy of CT and initial reverse transcriptase polymerase chain reaction (RT-PCR) for detecting COVID-19 infection.
METHODS
We searched three databases, PubMed, EMBASE, and EMCARE, to identify studies reporting diagnostic accuracy of both CT and RT-PCR in detecting COVID-19 infection between December 2019 and May 2020. For accurate comparison, only those studies that had patients undergoing both CT and RT-PCR were included. Pooled diagnostic accuracy of both the tests was calculated by using a bivariate random effects model.
RESULTS
Based on inclusion criteria, only 11 studies consisting of 1834 patients were included in the final analysis that reported diagnostic accuracy of both CT and RT-PCR, in the same set of patients. Sensitivity estimates for CT scan ranged from 0.69 to 1.00 and for RT-PCR varied ranging from 0.47 to 1.00. The pooled estimates of sensitivity for CT and RT-PCR were 0.91 [95% CI (0.84-0.97)] and 0.84 [95% CI (0.71-0.94)], respectively. On subgroup analysis, pooled sensitivity of CT and RT-PCR was 0.95 [95% CI (0.88-0.98)] and 0.91 [95% CI (0.80-0.96), = o.ooo1]. The pooled specificity of CT and RT-PCR was 0.31 [95% CI (0.035-0.84)] and 1.00 [95% CI (0.96-1.00)].
CONCLUSION
CT is more sensitive than RT-PCR in detecting COVID-19 infection, but has a very low specificity.
ADVANCES IN KNOWLEDGE
Since the results of a CT scan are available quickly, it can be used as an adjunctive initial diagnostic test for patients with a history of positive contact or epidemiological history.
Topics: COVID-19; COVID-19 Testing; Humans; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 33353381
DOI: 10.1259/bjr.20201039 -
Journal of Acquired Immune Deficiency... Mar 2022Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood.
METHODS
Standard databases (PubMed and Medline), conferences, and gray literature were searched until January 2019. The quality of evidence was evaluated using the Standards for Reporting Studies of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology, and to account for between-study variation.
RESULTS
We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots with that of plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared with that of plasma was 0.28 log10 copies/mL, whereas the difference in median viral load was 2.25 log10 copies/mL. More dried plasma spot values were undetectable compared with plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens were >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds.
DISCUSSION
Overall, dried plasma spot specimens performed relatively well compared with plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.
Topics: Dried Blood Spot Testing; HIV Infections; HIV-1; Humans; RNA, Viral; Sensitivity and Specificity; Treatment Failure; Viral Load
PubMed: 34732684
DOI: 10.1097/QAI.0000000000002855 -
Urology Journal Sep 2020To review the current literature on the presence of COVID-19 virus in the urine of infected patients and to explore the clinical features that can predict the presence... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To review the current literature on the presence of COVID-19 virus in the urine of infected patients and to explore the clinical features that can predict the presence of COVID-19 in urine.
MATERIALS AND METHODS
A systematic review of published literature between 30th December 2019 and 21st June 2020 was conducted on Pubmed, Google Scholar, Ovid, Scopus, and ISI web of science. Studies investigating urinary viral shedding of COVID-19 in infected patients were included. Two reviewers selected relative studies and performed quality assessment of individual studies. Meta-analysis was performed on the pooled case reports and cohort with a sample size of ≥ 9.
RESULTS
Thirty-nine studies were finally included in the systematic review; 12 case reports, 26 case series, and one cohort study. Urinary samples from 533 patients were investigated. Fourteen studies reported the presence of COVID-19 in the urinary samples from 24 patients. The crude overall rate of COVID-19 detection in urinary samples was 4.5%. Considering case series and cohorts with a sample size of ≥ 9, the estimated viral shedding frequency was 1.18 % (CI 95%: 0.14 - 2.87) in the meta-analysis. Urinary viral load in most reports were lower than rectal or oropharyngeal samples. In adult patients, urinary shedding of COVID-19 was commonly detected in patients with moderate to severe disease (16 adult patients with moderate or severe disease versus two adult patients with mild disease). In children, urinary viral shedding of COVID-19 was reported in 4 children who all suffered from mild disease. Urinary viral shedding of COVID-19 was detected from day 1 to day 52 after disease onset. The pathogenicity of virus isolated from urine has been demonstrated in cell culture media in one study while another study failed to reveal replication of isolated viral RNA in cell cultures. Urinary symptoms were not attributed to urinary viral shedding.
CONCLUSION
While COVID-19 is rarely detected in urine of infected individuals, infection transmission through urine still remains possible. In adult patients, infected urine is more likely in the presence of moderate or severe disease. Therefore, caution should be exerted when dealing with COVID-19 infected patients during medical interventions like endoscopy and urethral catheterization especially in symptomatic adult patients while in children caution should be exerted regardless of symptoms.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; RNA, Viral; SARS-CoV-2; Urinary Tract; Virus Shedding
PubMed: 32888186
DOI: 10.22037/uj.v16i7.6248 -
Clinical Microbiology and Infection :... Sep 2021Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological...
BACKGROUND
Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological tests detecting viral antigen or virus-specific antibodies.
OBJECTIVES
We provide an overview of the challenges towards serological testing for the most important emerging arboviruses, including Zika, dengue and chikungunya viruses.
SOURCES
We retrieved a data set on performance of commercially available antibody- and antigen-detecting tests from 89 peer-reviewed articles conducting a systematic literature research in PubMed.
CONTENT
We identified commonly used antibody- and antigen-detecting tests and analysed their overall performance. We discuss how timing of serological testing and the use of paired samples from acute and convalescent phases of infection are crucial to optimize diagnostic sensitivity and specificity. We then exemplify how serological diagnostics are challenged by the patient's infection history through the 'original antigenic sin' and cross-reactive antibodies in the context of global co-circulation of antigenically related viruses. We highlight how individual infection histories with different arboviruses and with other pathogens such as herpes viruses and Plasmodia can produce inaccurate test results. We show that rapid tests for antibody and antigen detection in point-of-care settings have a significantly lower sensitivity compared with laboratory-based tests such as ELISA. We show that the performance of antibody- and antigen-detecting tests varies greatly between tropical regions of endemic transmission and non-endemic regions. Finally, we highlight that test sensitivity and specificity have to be equilibrated carefully and frequently either of them must be prioritized over the other, depending on disease prevalence and intended use of tests.
IMPLICATIONS
For reliable serological diagnostics, it is essential to be aware of inherent test limitations. Although multiplexed testing and testing of convalescence samples can improve diagnostic performance, global spread of (re-)emerging viruses requires careful implementation and evaluation of serological testing and unambiguous results may not always be achievable.
Topics: Antibodies, Viral; Antigens, Viral; Arbovirus Infections; Arboviruses; Humans; Sensitivity and Specificity; Serologic Tests
PubMed: 34111589
DOI: 10.1016/j.cmi.2021.05.047 -
International Journal of Environmental... Jul 2020(1) Background: The global threat of Coronavirus disease 2019 (COVID-19) continues. The diversity of clinical characteristics and progress are reported in many countries... (Meta-Analysis)
Meta-Analysis
(1) Background: The global threat of Coronavirus disease 2019 (COVID-19) continues. The diversity of clinical characteristics and progress are reported in many countries as the duration of the pandemic is prolonged. We aimed to perform a novel systematic review and meta-analysis focusing on findings about correlations between clinical characteristics and laboratory features of patients with COVID-19. (2) Methods: We analyzed cases of COVID-19 in different countries by searching PubMed, Embase, Web of Science databases and Google Scholar, from the early stage of the outbreak to late March. Clinical characteristics, laboratory findings, and treatment strategies were retrospectively reviewed for the analysis. (3) Results: Thirty-seven ( = 5196 participants) COVID-19-related studies were eligible for this systematic review and meta-analysis. Fever, cough and fatigue/myalgia were the most common symptoms of COVID-19, followed by some gastrointestinal symptoms which are also reported frequently. Laboratory markers of inflammation and infection including C-reactive protein (CRP) (65% (95% confidence interval (CI) 56-81%)) were elevated, while lymphocyte counts were decreased (63% (95% CI 47-78%)). Meta-analysis of treatment approaches indicated that three modalities of treatment were predominantly used in the majority of patients with a similar prevalence, including antiviral agents (79%), antibiotics (78%), and oxygen therapy (77%). Age was negatively correlated with number of lymphocytes, but positively correlated with dyspnea, number of white blood cells, neutrophils, and D-dimer. Chills had been proved to be positively correlated with chest tightness, lung abnormalities on computed tomography (CT) scans, neutrophil/lymphocyte/platelets count, D-dimer and CRP, cough was positively correlated with sputum production, and pulmonary abnormalities were positively correlated with CRP. White blood cell (WBC) count was also positively correlated with platelet counts, dyspnea, and neutrophil counts with the respective correlations of 0.668, 0.728, and 0.696. (4) Conclusions: This paper is the first systematic review and meta-analysis to reveal the relationship between various variables of clinical characteristics, symptoms and laboratory results with the largest number of papers and patients until now. In elderly patients, laboratory and clinical characteristics indicate a more severe disease course. Moreover, treatments such as antiviral agents, antibiotics, and oxygen therapy which are used in over three quarters of patients are also analyzed. The results will provide "evidence-based hope" on how to manage this unanticipated and overwhelming pandemic.
Topics: Age Factors; Betacoronavirus; C-Reactive Protein; COVID-19; Chills; Coronavirus Infections; Cough; Dyspnea; Fibrin Fibrinogen Degradation Products; Humans; Inflammation; Leukocyte Count; Lymphocyte Count; Pandemics; Platelet Count; Pneumonia, Viral; SARS-CoV-2
PubMed: 32668763
DOI: 10.3390/ijerph17145026 -
The Journal of Hospital Infection Feb 2023Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant...
Viral cultures, cycle threshold values and viral load estimation for assessing SARS-CoV-2 infectiousness in haematopoietic stem cell and solid organ transplant patients: a systematic review.
BACKGROUND
Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation.
OBJECTIVES
To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients.
METHODS
LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1 November 2019 to 26 October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically.
RESULTS
Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms.
CONCLUSIONS
Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.
Topics: Humans; COVID-19; SARS-CoV-2; Viral Load; Organ Transplantation; Hematopoietic Stem Cells
PubMed: 36473552
DOI: 10.1016/j.jhin.2022.11.018 -
Journal of Medical Virology Apr 2021Previous studies reported the positive viral RNA among coronavirus disease-2019 (COVID-19) recovered patients. This study aimed to summarize the current evidence of... (Meta-Analysis)
Meta-Analysis
Previous studies reported the positive viral RNA among coronavirus disease-2019 (COVID-19) recovered patients. This study aimed to summarize the current evidence of factors associated with the risk of disease recurrence. PubMed and Embase were searched until September 2020 to identify studies assessing characteristics of recurrence and nonrecurrence subjects after discharge. Random-effect meta-analysis was used to pool estimates of odds ratio (OR) or weighted mean difference (WMD) and their 95% confidence intervals (CIs) across studies. Meta-analysis data were available for age, sex, hospital duration, disease severity, seven comorbidities, five symptoms, five indexes of blood routine, nine indexes of blood biochemistry, four treatment therapies, two antibodies, and history of high-risk contact. Among them, hospital duration of recurrence cases was significantly shorter than nonrecurrence subjects (WMD, -1.55 days; 95% CI, -2.66 to -0.45). Fatigue, positive Immunoglobulin M (IgM), and positive IgG were associated with an increased risk of recurrence cases, with ORs and 95% CIs of 4.06 (1.14-14.4), 2.95 (1.15-7.61), and 3.45 (1.58-7.54), respectively. In contrast, the odds of recurrence cases were observed to significantly lower in subjects with elevated lactate dehydrogenase and C-reactive protein, low lymphocyte count, steroid and arbidol use, with ORs (95% CIs) of 1.08 (0.27-4.37), 0.49 (0.27-0.97), 0.64 (0.42-0.97), 0.48 (0.25-0.96), and 0.48 (0.25-0.92), respectively. This study provided up-to-date evidence of several clinical and epidemiological characteristics in the association with COVID-19 recurrence cases. Further in-depth analyses for the causal effect of factors on re-positive viral RNA are needed for the management of discharged patients with COVID-19.
Topics: C-Reactive Protein; COVID-19; COVID-19 Nucleic Acid Testing; Databases, Factual; False Negative Reactions; Humans; Immunoglobulin M; RNA, Viral; Recurrence; SARS-CoV-2; Severity of Illness Index
PubMed: 33135788
DOI: 10.1002/jmv.26648 -
BMC Cancer May 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV)... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV) infection. We conducted a meta-analysis to estimate the efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the first-line treatment of the unresectable HCC and to evaluate the benefits of different geographic regions and etiology stratifications.
METHODS
Randomized clinical trials published up to 12th November 2022 were searched by online databases. Moreover, effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted from included studies. Pooled odds ratio (OR) and 95% CI for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were calculated.
RESULTS
A total of 3057 patients from five phase III randomized clinical trials were collected and reviewed for this meta-analysis. The pooled HR of OS (HR = 0.71; 95% CI: 0.60-0.85) and PFS (HR = 0.64; 95% CI: 0.53-0.77) demonstrated significantly better benefit in PD-1/PD-L1 inhibitors combination group than targeted monotherapy to treat unresectable HCC. In addition, combination therapy showed better ORR and DCR, with ORs of 3.29 (95% CI: 1.92-5.62) and 1.88 (95% CI: 1.35-2.61), respectively. The subgroup analysis indicated that PD-1/PD-L1 inhibitors combination therapy was significantly superior to anti-angiogenic monotherapy for HBV-related HCC in terms of OS (HR = 0.64; 95% CI: 0.55-0.74) and PFS (HR = 0.53; 95% CI:0.47-0.59), while there was no significant difference in patients with HCV (OS, HR = 0.81, p = 0.1) or non-viral (OS, HR = 0.91, p = 0.37; PFS, HR = 0.77, p = 0.05).
CONCLUSIONS
Meta-analysis revealed for the first-time that PD-1/PD-L1 inhibitors combination therapy for unresectable HCC was associated with better clinical outcomes than anti-angiogenic monotherapy, especially for HBV infection and Asian population.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B; Hepatitis B virus; Immune Checkpoint Inhibitors; Liver Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 37226111
DOI: 10.1186/s12885-023-10960-w