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Advances in Therapy Sep 2022Respiratory syncytial virus (RSV)-associated diseases have caused an estimated 1.8 million hospital admissions and 40,000 deaths among children. RSV can cause lower... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Respiratory syncytial virus (RSV)-associated diseases have caused an estimated 1.8 million hospital admissions and 40,000 deaths among children. RSV can cause lower respiratory tract infections (LRTIs) in all age groups, adults with comorbidities, and immunocompromised patients. The aim was to summarize the evidence concerning efficacy and safety of ribavirin in subjects diagnosed with RSV associated with LRTI.
METHODS
A systematic review and meta-analysis were performed. Eligible studies were observational (> 10 subjects) and randomized-controlled trials of subjects with aerosol/oral ribavirin for RSV-LRTI. Comparator was supportive care or placebo. Systematic search on PubMed, Cochrane Library, and Web of Science databases was conducted between January 2001 and January 2022. PROSPERO register number: CRD42022308147.
RESULTS
After retrieving 907 studies, 10 observational studies and 1 randomized controlled trial were included (4/11 high quality of evidence). Seven studies included subjects with haematological malignancy/stem cell transplant, two lung transplants, and two healthy individuals. A total of 788 subjects diagnosed with RSV infection were included; 14.3% of them presented with only LRTI. Among 445 subjects treated with ribavirin, 195 (43.8%) received an aerosolized formulation. Pooled meta-analysis showed no differences in mortality [risk ratio (RR): 0.63; 95% confidence interval (CI): 0.28-1.42] in all subjects treated with aerosol/oral ribavirin compared to supportive care. In subgroup analysis, mortality was significantly lower in haematological subjects (RR: 0.32; 95% CI: 0.14-0.71), but did not differ significantly in lung transplant recipients (RR: 0.89; 95% CI 0.31-2.56). Oral ribavirin (vs. supportive care) was associated with increased viral clearance (RR: 2.60; 95% CI: 1.35-4.99). Seventeen adverse events were reported among 119 subjects, but none were severe.
CONCLUSION
Ribavirin should be considered for treatment of RSV-LRTI in haematological subjects. There is a lack of evidence to support its use in lung transplant recipients. Oral formulation appears to be an easier, safe, and cost-effective alternative to aerosolized ribavirin. Further advances needs to focus on newer antivirals.
Topics: Adult; Antiviral Agents; Child; Humans; Respiratory Aerosols and Droplets; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Ribavirin
PubMed: 35876973
DOI: 10.1007/s12325-022-02256-5 -
Clinical Microbiology and Infection :... Jul 2022Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies.
OBJECTIVES
We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions.
DATA SOURCES
PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021.
STUDY ELIGIBILITY CRITERIA
ICU cohort studies and CAPA case series including ≥3 patients were included.
PARTICIPANTS
Adult patients in ICUs with COVID-19.
INTERVENTIONS
Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews.
METHODS
We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis.
RESULTS
Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival.
CONCLUSIONS
The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.
Topics: Adult; Antifungal Agents; COVID-19; Critical Care; Humans; Intensive Care Units; Pulmonary Aspergillosis
PubMed: 35150878
DOI: 10.1016/j.cmi.2022.01.027 -
International Journal of Infectious... Sep 2022Identifying pathogens in patients with pulmonary infection (PI) has always been a major challenge in medicine. Compared with sputum and throat swabs, bronchoalveolar... (Meta-Analysis)
Meta-Analysis Review
Diagnostic performance of metagenomic next-generation sequencing for the detection of pathogens in bronchoalveolar lavage fluid in patients with pulmonary infections: Systematic review and meta-analysis.
OBJECTIVES
Identifying pathogens in patients with pulmonary infection (PI) has always been a major challenge in medicine. Compared with sputum and throat swabs, bronchoalveolar lavage fluid (BALF) can better reflect the actual state of the lungs. However, there has not been a meta-analysis of the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) in detecting pathogens in BALF from patients with PIs.
METHODS
Data sources were PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure. The pooled sensitivity and specificity were estimated using random-effects or fixed-effect models. Subgroup analysis was performed to reveal the effect of potential explanatory factors on the diagnostic performance measures.
RESULTS
The pooled sensitivity was 78% (95% confidence interval [CI]: 67-87%; I = 92%) and the pooled specificity was 77% (95% CI: 64-94%; I = 74%) for mNGS. Subgroup analyses for the sensitivity of mNGS revealed that patients with PIs who were severely ill or immunocompromised significantly affected heterogeneity (P < 0.001). The positive detection rate of mNGS for pathogens in BALF of severely or immunocompromised pulmonary-infected patients was 92% (95% CI: 78-100%).
CONCLUSION
mNGS has high diagnostic performance for BALF pathogens in patients with PIs, especially in critically ill or immunocompromised patients.
Topics: Bronchoalveolar Lavage Fluid; High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 35907477
DOI: 10.1016/j.ijid.2022.07.054 -
Pulmonology 2021Evidence suggests lungs as the organ most affected by coronavirus disease 2019 (COVID-19). The literature on previous coronavirus infections reports that patients may... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests lungs as the organ most affected by coronavirus disease 2019 (COVID-19). The literature on previous coronavirus infections reports that patients may experience persistent impairment in respiratory function after being discharged. Our objective was to determine the prevalence of restrictive pattern, obstructive pattern and altered diffusion in patients post-COVID-19 infection and to describe the different evaluations of respiratory function used with these patients.
METHODS
A systematic review was conducted in five databases. Studies that used lung function testing to assess post-infection COVID-19 patients were included for review. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence.
RESULTS
Of the 1973 reports returned by the initial search, seven articles reporting on 380 patients were included in the data synthesis. In the sensitivity analysis, we found a prevalence of 0.39 (CI 0.24-0.56, p < 0.01, I = 86%), 0.15 (CI 0.09-0.22, p = 0.03, I = 59%), and 0.07 (CI 0.04-0.11, p = 0.31, I = 16%) for altered diffusion capacity of the lungs for carbon monoxide (DL), restrictive pattern and obstructive pattern, respectively.
CONCLUSION
Post-infection COVID-19 patients showed impaired lung function; the most important of the pulmonary function tests affected was the diffusion capacity.
Topics: COVID-19; Forced Expiratory Volume; Humans; Lung; Pulmonary Diffusing Capacity; Respiratory Function Tests; SARS-CoV-2; Total Lung Capacity; Vital Capacity; Post-Acute COVID-19 Syndrome
PubMed: 33262076
DOI: 10.1016/j.pulmoe.2020.10.013 -
Autoimmunity Reviews Nov 2021The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of... (Meta-Analysis)
Meta-Analysis Review
The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection and PCS were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8-55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143-258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2-1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.
Topics: Adult; Antibodies, Viral; COVID-19; Female; Humans; Immunoglobulin G; Lung; Middle Aged; SARS-CoV-2
PubMed: 34509649
DOI: 10.1016/j.autrev.2021.102947 -
International Journal of Infectious... Dec 2022To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. (Review)
Review
OBJECTIVES
To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.
METHODS
A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.
RESULTS
Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).
CONCLUSION
Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium abscessus; Lung Diseases; Pneumonia
PubMed: 36244600
DOI: 10.1016/j.ijid.2022.10.013 -
Clinical Microbiology and Infection :... Apr 2021Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
BACKGROUND
Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
OBJECTIVES
Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection.
SOURCES
We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals.
CONTENT
Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression.
IMPLICATIONS
We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions.
Topics: Algorithms; Anti-Bacterial Agents; Humans; Nocardia; Nocardia Infections
PubMed: 33418019
DOI: 10.1016/j.cmi.2020.12.019 -
Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal.BMJ (Clinical Research Ed.) Apr 2020To review and appraise the validity and usefulness of published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients...
OBJECTIVE
To review and appraise the validity and usefulness of published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at increased risk of covid-19 infection or being admitted to hospital with the disease.
DESIGN
Living systematic review and critical appraisal by the COVID-PRECISE (Precise Risk Estimation to optimise covid-19 Care for Infected or Suspected patients in diverse sEttings) group.
DATA SOURCES
PubMed and Embase through Ovid, up to 1 July 2020, supplemented with arXiv, medRxiv, and bioRxiv up to 5 May 2020.
STUDY SELECTION
Studies that developed or validated a multivariable covid-19 related prediction model.
DATA EXTRACTION
At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool).
RESULTS
37 421 titles were screened, and 169 studies describing 232 prediction models were included. The review identified seven models for identifying people at risk in the general population; 118 diagnostic models for detecting covid-19 (75 were based on medical imaging, 10 to diagnose disease severity); and 107 prognostic models for predicting mortality risk, progression to severe disease, intensive care unit admission, ventilation, intubation, or length of hospital stay. The most frequent types of predictors included in the covid-19 prediction models are vital signs, age, comorbidities, and image features. Flu-like symptoms are frequently predictive in diagnostic models, while sex, C reactive protein, and lymphocyte counts are frequent prognostic factors. Reported C index estimates from the strongest form of validation available per model ranged from 0.71 to 0.99 in prediction models for the general population, from 0.65 to more than 0.99 in diagnostic models, and from 0.54 to 0.99 in prognostic models. All models were rated at high or unclear risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, high risk of model overfitting, and unclear reporting. Many models did not include a description of the target population (n=27, 12%) or care setting (n=75, 32%), and only 11 (5%) were externally validated by a calibration plot. The Jehi diagnostic model and the 4C mortality score were identified as promising models.
CONCLUSION
Prediction models for covid-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that almost all pubished prediction models are poorly reported, and at high risk of bias such that their reported predictive performance is probably optimistic. However, we have identified two (one diagnostic and one prognostic) promising models that should soon be validated in multiple cohorts, preferably through collaborative efforts and data sharing to also allow an investigation of the stability and heterogeneity in their performance across populations and settings. Details on all reviewed models are publicly available at https://www.covprecise.org/. Methodological guidance as provided in this paper should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, prediction model authors should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline.
SYSTEMATIC REVIEW REGISTRATION
Protocol https://osf.io/ehc47/, registration https://osf.io/wy245.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 3 of the original article published on 7 April 2020 (BMJ 2020;369:m1328). Previous updates can be found as data supplements (https://www.bmj.com/content/369/bmj.m1328/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
Topics: COVID-19; Coronavirus; Coronavirus Infections; Disease Progression; Hospitalization; Humans; Models, Theoretical; Multivariate Analysis; Pandemics; Pneumonia, Viral; Prognosis
PubMed: 32265220
DOI: 10.1136/bmj.m1328 -
Clinical Microbiology and Infection :... Jun 2023Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic.
OBJECTIVES
To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis.
METHODS OF DATA SYNTHESIS
Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality.
DATA SOURCES
PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE.
STUDY ELIGIBILITY CRITERIA
Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022.
PARTICIPANTS
Adults who developed mucormycosis during or after COVID-19.
INTERVENTIONS
Patients with and without individual clinical variables were compared.
ASSESSMENT OF RISK OF BIAS
Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies.
RESULTS
Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780).
CONCLUSION
Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.
Topics: Adult; Humans; Aged; Mucormycosis; Coinfection; Pandemics; COVID-19; Hospitalization
PubMed: 36921716
DOI: 10.1016/j.cmi.2023.03.008 -
The Lancet. Infectious Diseases Apr 2023In 2020, an estimated total of 155 million people had survived tuberculosis. Among this number, a sizable proportion have considerable post-tuberculosis morbidity, as... (Review)
Review
In 2020, an estimated total of 155 million people had survived tuberculosis. Among this number, a sizable proportion have considerable post-tuberculosis morbidity, as shown for the adult population. This systematic review aims to identify the spectrum and prevalence of post-tuberculosis sequelae in children and adolescents. Four databases were systematically searched from database inception to Feb 7, 2022, for literature on post-treatment outcomes of tuberculosis acquired during childhood. Of the 4613 identified publications, 71 studies were included in this systematic review. Studies on cohorts with comparably rare (most of which were extrapulmonary) tuberculosis presentations, such as spinal tuberculosis and tuberculous meningitis were over-represented; however, no study assessed long-term sequelae in a cohort with an average childhood tuberculosis spectrum. The descriptive analysis includes long-term outcomes of 3529 paediatric patients 1 month to 36 years after confirmed (47%) or clinical (53%) tuberculosis. In a considerable proportion of children, a broad spectrum of post-tuberculosis sequelae were identified, ranging from radiological residua after pulmonary tuberculosis, to disabling deformities after musculoskeletal and cutaneous tuberculosis, to somatic and psychosocial impairment after tuberculous meningitis. A better understanding and comprehensive assessment of post-tuberculosis sequelae in children are needed to improve tuberculosis care beyond antituberculous treatment.
Topics: Adult; Child; Humans; Adolescent; Tuberculosis, Meningeal; Tuberculosis, Pulmonary; Morbidity; Prevalence; Tuberculosis, Cutaneous; Tuberculosis, Extrapulmonary
PubMed: 36963920
DOI: 10.1016/S1473-3099(23)00004-X