Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak.It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.
Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.
Successful detection of SARS-COV-2 in wastewater suggests the potential utility of wastewater-based epidemiology (WBE) for COVID-19 community surveillance. This systematic review aims to assess the performance of wastewater surveillance as early warning system of COVID-19 community transmission. A systematic search was conducted in PubMed, Medline, Embase and the WBE Consortium Registry according to PRISMA guidelines for relevant articles published until 31st July 2021. Relevant data were extracted and summarized. Quality of each paper was assessed using an assessment tool adapted from Bilotta et al.'s tool for environmental science. Of 763 studies identified, 92 studies distributed across 34 countries were shortlisted for qualitative synthesis. A total of 26,197 samples were collected between January 2020 and May 2021 from various locations serving population ranging from 321 to 11,400,000 inhabitants. Overall sample positivity was moderate at 29.2% in all examined settings with the spike (S) gene having maximum rate of positive detections and nucleocapsid (N) gene being the most targeted. Wastewater signals preceded confirmed cases by up to 63 days, with 13 studies reporting sample positivity before the first cases were detected in the community. At least 50 studies reported an association of viral load with community cases. While wastewater surveillance cannot replace large-scale diagnostic testing, it can complement clinical surveillance by providing early signs of potential transmission for more active public health responses. However, more studies using standardized and validated methods are required along with risk analysis and modelling to understand the dynamics of viral outbreaks.
Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear.Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immuneinflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined. Measurements and Main Results:A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.
Background The COVID-19 pandemic has elicited imposition of some form of travel restrictions by almost all countries in the world. Most restrictions currently persist, although some have been gradually eased. It remains unclear if the trade-off from the unprecedented disruption to air travel was well worth for pandemic containment. Method A comparative analysis was conducted on Singapore, Taiwan, Hong Kong and South Korea’s COVID-19 response. Data on COVID-19 cases, travel-related and community interventions, socio-economic profile were consolidated. Trends on imported and local cases were analyzed using computations of moving averages, rate of change, particularly in response to distinct waves of travel-related interventions due to the outbreak in China, South Korea, Iran & Italy, and Europe. Results South Korea’s travel restrictions were observed to be consistently more lagged in terms of timeliness and magnitude, with their first wave of travel restrictions on flights departing from China implemented 34 days after the outbreak in Wuhan, compared to 22–26 days taken by Singapore, Taiwan and Hong Kong. South Korea’s restrictions against all countries came after 91 days, compared to 78–80 days for the other three countries. The rate of change of imported cases fell by 1.08–1.43 across all four countries following the first wave of travel restrictions on departures from China, and by 0.22–0.52 in all countries except South Korea in the fifth wave against all international travellers. Delayed rate of change of local cases resulting from travel restrictions imposed by the four countries with intrinsic importation risk, were not observed. Conclusions Travel restriction was effective in preventing COVID-19 case importation in early outbreak phase, but may still be limited in preventing general local transmission. The impact of travel restrictions, regardless of promptness, in containing epidemics likely also depends on the effectiveness of local surveillance and non-pharmaceutical interventions concurrently implemented.
Dengue is a rapidly spreading mosquito-borne flavivirus infection that is prevalent in tropical and sub-tropical regions. Humans are known to be the main reservoir host maintaining the epidemic cycles of dengue but it is unclear if dengue virus is also maintained in a similar enzootic cycle. The systematic review was conducted in accordance to Cochrane's PRISMA recommendations. A search was done on PubMed, EMBASE, Scopus and Cochrane Library. Key data on animal dengue positivity was extracted and classified according to animal type and diagnostic modes. Of the 3818 articles identified, 56 articles were used in this review. A total of 16,333 animals were tested, 1817 of which were positive for dengue virus by RT-PCR or serology. Dengue positivity was detected in bats (10.1%), non-human primates (27.3%), birds (11%), bovid (4.1%), dogs (1.6%), horses (5.1%), pigs (34.1%), rodents (3.5%), marsupials (13%) and other small animals (7.3%). While majority of dengue positivity via serology suggests potential enzootic transmission, but regular dengue virus spillback cannot be excluded. With the exception of bats, acute infection among animals is limited. Further investigation on animals is critically required to better understand their role as potential reservoir in dengue transmission.
Background: Acute respiratory illnesses (ARIs) are the most common respiratory infectious diseases among humans globally. Surgical mask (SM) wearing has been shown to be effective in reducing ARI among healthcare workers. However, the effectiveness of SM in reducing ARI in the non-healthcare settings remains unclear. This review aims to summarize and assess the association between SM wearing and ARI incidence, from existing interventional and observational studies conducted in non-healthcare settings. Methods: Systematic literature searches conducted in PubMed, Cochrane Library, and Embase databases identified 503 unique studies. After screening, 15 studies (5 randomized controlled trials and 10 observational studies) were assessed for reporting and methodological qualities. Proportions of ARI episodes in each group and adjusted summary statistics with their relevant 95% CIs were extracted. Data from 10 observational studies were pooled using the generic inverse variance method. Results: A total of 23,892 participants between 7 and 89 years old involved across 15 studies from 11 countries were involved. Key settings identified were Hajj, schools, and in-flight settings. A modest but non-significant protective effect of SM on ARI incidence was observed (pooled OR 0.96, 95% CI 0.8-1.15). Subgroup analysis according to age group, outcome ascertainment and different non-healthcare settings also revealed no significant associations between SM use and ARI incidence. Conclusion: Surgical mask wearing among individuals in non-healthcare settings is not significantly associated with reduction in ARI incidence in this meta-review.
Background: Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. Methods: Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. Findings: A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. Conclusion: The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.
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