Clinical efficacy and effectiveness of alternative varicella vaccination strategies: An overview of reviews.

A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of dosing schedule (one- or two-dose), type of vaccine(s) recommended (monovalent, quadrivalent measles-mumps-rubella-varicella, or both), age at vaccination, and dosing interval for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the clinical efficacy/effectiveness of alternative varicella vaccination strategies. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. A total of 20 reviews were included in the overview; 17 assessed the efficacy/effectiveness of one-dose strategies and 10 assessed the efficacy/effectiveness of two-dose strategies. Although the quality of most reviews was deemed 'critically low', there was clear and consistent evidence that vaccination is very effective at reducing varicella. While the analysis was restricted due to lack of detail in reporting of the reviews, the evidence suggests that two-dose strategies are more efficacious/effective than one-dose strategies in preventing varicella of any severity, but that both strategies have similar high efficacy/effectiveness in preventing moderate or severe varicella. Based on this evidence in this overview of reviews, a key consideration for policymakers on the possible introduction of a childhood varicella vaccination programme and the choice between a one- or two-dose strategy, will be whether the objective of a programme is to prevent varicella of any severity or to prevent moderate to severe varicella.

Safety of varicella vaccination strategies: An overview of reviews.

The safety of new vaccines under development as well as existing vaccines is a key priority for national and international public health agencies. A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of the number of doses, type of vaccine(s) recommended, age at vaccination and interval between doses for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the safety of varicella vaccination strategies. The review was restricted to immunocompetent children aged 9 months to 6 years inclusive. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. Overlap of included reviews was also assessed. A total of 17 reviews, incorporating both the monovalent varicella only and quadrivalent measles-mumps-rubella-varicella (MMRV) vaccines were included in the overview; six assessed the safety of one-dose strategies, four assessed the safety of two-dose strategies and 14 reviews did not specify the dosing strategy. The evidence suggests that mild local and systemic reactions are relatively common with varicella vaccination. Febrile seizures are also possible adverse effects of both the monovalent and quadrivalent MMRV vaccine, but serious adverse reactions are rare. While most reviews contained methodological flaws, and analysis by vaccine type and dosing strategy was restricted due to lack of detail in reporting of the reviews, there was clear and consistent evidence from a substantial evidence base, comprising 34 randomised controlled trials and 62 other primary studies/reviews, that varicella vaccination is safe.

Diagnostic accuracy of 18F Prostate Specific Membrane Antigen (PSMA) PET-CT radiotracers in staging and restaging of high-risk prostate cancer patients and patients with biochemical recurrence: protocol for an overview of reviews.

Background: Correct staging and risk stratification is essential in ensuring prostate cancer patients are offered the most appropriate treatment. Interest has been growing in the use of radiotracers targeting prostate specific membrane antigen (PSMA), including the use of 18F-PSMA PET-CT, as part of the primary staging or restaging of prostate cancer. Preliminary scoping identified a number of relevant systematic reviews and meta-analyses; however, individually, these each appear to look at only part of the picture. An overview of reviews aims to systematically identify, appraise and synthesise multiple systematic reviews, related to a relevant research question or questions. We present a protocol for an overview of reviews, which aims to collate existing evidence syntheses exploring the diagnostic accuracy of 18F-PSMA in staging and restaging of prostate cancer. It also aims to highlight evidence gaps in prostate cancer staging or restaging. Methods: This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for systematic review protocols (PRISMA-P). The search strategy will be designed in consultation with a librarian. Searches will be performed in Medline (EBSCO), Embase (Ovid), Google Scholar and the Cochrane Database for Systematic Reviews, supplemented by a targeted grey literature search, forward citation searching and searching reference lists of included reviews. No language or date restrictions will be applied to the eligibility criteria or the search strategy. Title & abstract and full text screening will be performed independently by two reviewers. Data will be extracted by one reviewer and checked in full by a second reviewer. Quality appraisal will be performed using the Risk of Bias in Systematic Reviews (ROBIS) tool independently by two reviewers, and results will be narratively synthesised. Conclusions: This overview of reviews may be of interest to healthcare professionals, academics and health policy decision-makers. Registration: OSF (September 7, 2023).

Incidence and type of restrictive practice use in nursing homes in Ireland.

BACKGROUND: Use of restrictive practices (RP) in care settings may sometimes be warranted but can also conflict with human rights. Research to date has focused primarily on physical and chemical RP, however other forms are also used. Better understanding of practice can inform RP reduction. This study describes the incidence of all types of RP use reported from nursing homes in Ireland. METHODS: RP notifications from nursing homes reported in 2020 were extracted from the Database of Statutory Notifications from Social Care in Ireland. The primary outcome measurement was the national incidence of use (frequency of RP/occupancy per 1000 residents) of categories and types of RP. Secondary outcome measurements such as percentage of facilities reporting use and quarterly median incidence of use in these facilities were calculated. RESULTS: Seventy thousand six hundred sixty-three RP uses were notified from 608 facilities (33,219 beds). National incidence of RP use per 1000 residents was, all categories: 2465.1, environmental: 1324.5, physical: 922.5, chemical: 141.1; 'other': 77.0. The most frequently used RPs per category were, environmental: door locks; physical: bedrails; chemical (where drug specified): antipsychotics; 'other': privacy. 90.5% of nursing homes reported using at least one type of RP in the 12-month period. Quarterly incidence of any RP use in these facilities was median 1.642 (IQR: 0.018 to 18.608) per bed. CONCLUSIONS: Nursing homes in Ireland regularly use RP; only 9.5% reported no RP use in the 12-month period. A wide variety of types of RP were reported. Environmental and 'other' (largely psychosocial) RP contributed notably to total RP use and warrant attention alongside the traditional focus on physical and chemical RP. Policy implications include the need for more comprehensive RP definitions.

Rationalising Antipsychotic Prescribing in Dementia (RAPID) complex intervention: A mixed-methods feasibility intervention study.

Background: To help address the issue of inappropriate antipsychotic prescribing to nursing home residents with dementia, the 'Rationalising Antipsychotic Prescribing in Dementia' (RAPID) complex intervention was developed, comprising staff education and training, academic detailing and a novel resident assessment tool. Objectives: The primary objective was to assess the feasibility and acceptability of the RAPID complex intervention in a nursing home setting. The secondary objective was to describe associated trends in psychotropic prescribing, falls, and behavioural symptoms. Methods: A mixed-methods feasibility intervention study in one large nursing home in Ireland was undertaken between 07/2017 and 01/2018. Focus groups and semi-structured interviews were conducted with nursing home staff and GPs at the end of the 3-month follow up period to assess participants' experience of the intervention. Quantitative measurements included pre- and post-course evaluation and psychotropic prescribing rates. Results: Sixteen nursing home staff members attended the two education and training days (21% attendance rate), and four GPs participated in the academic detailing sessions (100% attendance rate). Participants of the focus groups and interviews (n = 18) found the education and training beneficial for their work and expressed a desire to continue educating new staff after the study's completion. However, there was limited usage of the resident assessment tool. Participants also offered recommendations to enhance the intervention.The proportion of dementia residents prescribed at least one regular antipsychotic was stable over the 3-months pre-intervention at 45% (n = 18), and at baseline at 44% (n = 19) but decreased slightly to 36% (n = 14) at 3-months post-intervention. At the same time the absolute number of 'PRN' psychotropics administered monthly to dementia residents decreased substantially from 90 at baseline to 69 at 3-months post-intervention. Conclusion: The RAPID complex intervention was broadly feasible to conduct and may be acceptable to stakeholders. However, before it can be evaluated in larger scale studies, certain protocol modifications and further exploratory work are required to improve implementation.

Incidence and type of restrictive practice use in residential disability facilities in Ireland, a cross-sectional study.

Restrictive practices (RPs) are a contentious issue in health and social care services. While use may be warranted in some instances, there are risks and concerns around human rights infringements. There are limited data available on the types and incidences of RPs used in health and social care services internationally. The objective of this study is to describe the type of RPs and incidence of use in disability residential care facilities (RCFs) in Ireland. RP notifications from disability RCFs reported from November 2019 to October 2020 were extracted from the Database of Statutory Notifications from Social Care in Ireland. National frequency and incidence of use of categories and type of RPs were calculated. The number and percentage of disability RCFs reporting RP use, along with the mean annual incidence of use, were also calculated. A total of 48,877 uses of RPs were notified from 1387 disability RCFs (9487 beds) during the 12-month period. The national incidence of RPs use per 1000 beds was as follows: all categories: 5152.0, environmental: 2988.2, physical: 1403.0, other: 527.0 and chemical: 233.8. The most frequently used RPs for each category was as follows: environmental: door locks, physical: other physical, other: liberty and autonomy and chemical: anxiolytics. Most RCFs (81.7%) reported at least one RPs use. The median incidence of any RPs per 1000 beds in these RCFs was 4.75 (IQR: 2.00 to 51.66). Usage of RPs was generally low, although some RCFs reported relatively high usage. Nationally, on average, five RPs were applied per resident over 12 months; environmental contributing to more than half. These findings can be used to inform policy, measure progress in reducing RPs use and for cross-jurisdiction comparisons.

Effectiveness of rapid antigen testing for screening of asymptomatic individuals to limit the transmission of SARS-CoV-2: A rapid review.

Rapid antigen detection tests (RADTs) offer advantages over gold-standard reverse transcription polymerase chain reaction (RT-PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS-CoV-2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS-CoV-2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population-level screening, four for pre-event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS-CoV-2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real-world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals.

Transmission of SARS-CoV-2 by children: a rapid review, 30 December 2019 to 10 August 2020.

BackgroundThe role of children in the transmission of SARS-CoV-2 during the early pandemic was unclear.AimWe aimed to review studies on the transmission of SARS-CoV-2 by children during the early pandemic.MethodsWe searched MEDLINE, Embase, the Cochrane Library, Europe PubMed Central and the preprint servers medRxiv and bioRxiv from 30 December 2019 to 10 August 2020. We assessed the quality of included studies using a series of questions adapted from related tools. We provide a narrative synthesis of the results.ResultsWe identified 28 studies from 17 countries. Ten of 19 studies on household and close contact transmission reported low rates of child-to-adult or child-to-child transmission. Six studies investigated transmission of SARS-CoV-2 in educational settings, with three studies reporting 183 cases from 14,003 close contacts who may have contracted COVID-19 from children index cases at their schools. Three mathematical modelling studies estimated that children were less likely to infect others than adults. All studies were of low to moderate quality.ConclusionsDuring the early pandemic, it appeared that children were not substantially contributing to household transmission of SARS-CoV-2. School-based studies indicated that transmission rates in this setting were low. Large-scale studies of transmission chains using data collected from contact tracing and serological studies detecting past evidence of infection would be needed to verify our findings.

Pharmacological interventions to prevent Covid-19 disease: A rapid review.

The aim of this rapid review was to determine the effectiveness of pharmacological interventions (excluding vaccines) to prevent coronavirus disease 2019 (Covid-19) or reduce the severity of disease. A systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints was undertaken from 1 January 2020 to 17 August 2021. Four randomised controlled trials (RCTs) and one non-RCT were included; three trials (two RCTs and one non-RCT) tested ivermectin with or without carrageenan. While all reported some potential protective effect of ivermectin, these trials had a high risk of bias and the certainty of evidence was deemed to be 'very low'. One RCT tested bamlanivimab compared to placebo and reported a significantly reduced incidence of Covid-19 in the intervention group; this trial had a low risk of bias however the certainty of evidence was deemed 'very low'. The fifth RCT tested casirivimab plus imdevimab versus placebo and reported that the combination of monoclonal antibodies significantly reduced the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, viral load, duration of symptomatic disease and the duration of a high viral load; this trial was deemed to have a low risk of bias, and the certainty of evidence was 'low'. The designations 'low' and 'very low' regarding the certainty of evidence indicate that the estimate of effect is uncertain and therefore is unsuitable for informing decision-making. At the time of writing, there is insufficient high quality evidence to support the use of pharmacological interventions to prevent Covid-19.

Effectiveness of public health measures to prevent the transmission of SARS-CoV-2 at mass gatherings: A rapid review.

Mass gatherings play an important role in society, but since the onset of the Covid-19 pandemic, they have generally been restricted in order to mitigate transmission of SARS-CoV-2. The aim of this study was to summarise the evidence regarding the effectiveness of public health measures at preventing the transmission of SARS-CoV-2 at mass gatherings, and hence inform guidance on the organisation of these events. A rapid review was undertaken in Cochrane, Embase (OVID), Medline (OVID), Google, Web of Science and Europe PMC from 1 January 2020 to 3 June 2021. Of the identified 1,624 citations, 14 articles referring to 11 unique studies were included. This rapid review found evidence from 11 studies (involving approximately 30,482 participants) that implementing a range of measures may reduce the risk of SARS-CoV-2 transmission at mass gatherings; however, it is unlikely that this risk can be eliminated entirely. All studies adopted a layered mitigation approach involving multiple measures, which may be more effective than relying on any single measure. The number and intensity of measures implemented varied across studies, with most implementing resource intense measures. Importantly, all included studies were only of 'fair' to 'poor' quality. In conclusion, there is currently limited evidence on the effectiveness of measures to prevent SARS-CoV-2 transmission at mass gatherings. As mass gatherings recommence, continued adoption of known mitigation measures is required to limit the risk of transmission, as well as ongoing research and surveillance to monitor the potential impact of these events on the wider population and healthcare system.

Improving the appropriateness of psychotropic prescribing for nursing home residents with dementia: an overview of reviews.

OBJECTIVES: Psychotropic medications are commonly inappropriately prescribed for people with dementia (PwD) residing in nursing homes. This population is often multi-morbid, receiving multiple medications and therefore at an increased risk of mortality. This overview aimed to collate all synthesised quantitative, qualitative, and mixed-method evidence pertaining to the effectiveness of interventions aimed at reducing inappropriate psychotropic prescribing for nursing home residents with dementia; the perceived barriers and facilitators to the implementation of these interventions; and the attitudes and experiences of stakeholders toward prescribing. Method: An overview of reviews was conducted (PROSPERO protocol registration CRD42020187288). Five databases were systematically searched from January 2010 through June 2020, supplemented by grey literature searching. Reviews presenting evidence pertaining to either randomised controlled trials (RCT) aiming to reduce inappropriate prescribing or qualitative/mixed method studies of stakeholder views, were included. RESULTS: Of 273 records identified, 11 systematic reviews were included. The quality of reviews ranged from critically low to moderate. There was mixed evidence for the use of education-only interventions. Multicomponent interventions (typically staff education combined with organisational and structural components), medication review, and interventions aimed at cultural change were evidenced as effective compared to care as usual. Stakeholders cited the importance of multidisciplinary collaboration and targeting organisational climate in changing psychotropic prescribing behaviours. CONCLUSIONS: The inappropriate use of psychotropic medications in nursing homes for PwD is a complex issue with many contextual factors. The evidence suggests a comprehensive approach, targeting organisational climate and multidisciplinary collaboration, along with staff education and training, may be an effective strategy.

Developing a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia.

Background: Antipsychotics are commonly prescribed to people living with dementia in nursing home settings, despite strong guideline recommendations against their use except in limited circumstances. We aimed to transparently describe the development process for a complex intervention targeting appropriate requesting and prescribing of antipsychotics to nursing home residents with dementia in Ireland, by nurses and general practitioners (GPs) respectively. Methods: We report the development process for the 'Rationalising Antipsychotic Prescribing in Dementia' (RAPID) complex intervention, in accordance with the 'Guidance for reporting intervention development studies in health research' (GUIDED) checklist.  The UK Medical Research Council framework for developing and evaluating complex interventions guided our overall approach, incorporating evidence and theory into the intervention development process. To unpack the intervention development process in greater detail, we followed the Behaviour Change Wheel approach. Guided by our stakeholders, we conducted three sequential studies (systematic review and qualitative evidence synthesis, primary qualitative study and expert consensus study), to inform the intervention development. Results: The RAPID complex intervention was developed in collaboration with a broad range of stakeholders, including people living with dementia and family carers, between 2015 and 2017. The finalised RAPID complex intervention was comprised of the following three components; 1) Education and training sessions with nursing home staff; 2) Academic detailing with GPs; 3) Introduction of an assessment tool to the nursing home. Conclusions: This paper describes the steps used by the researchers to develop a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia in Ireland, according to the GUIDED checklist. We found that the GUIDED checklist provided a useful way of reporting all elements in a cohesive manner and complemented the other tools and frameworks used. Transparency in the intervention development processes can help in the translation of evidence into practice.

The relationship between procedural volume and patient outcomes for percutaneous coronary interventions: a systematic review and meta-analysis.

BACKGROUND: The relationship between procedural volume and outcomes for percutaneous coronary interventions (PCI) is contentious, with previous reviews suggesting an inverse volume-outcome relationship. The aim of this study was to systematically review contemporary evidence to re-examine this relationship. METHODS: A systematic review and meta-analysis was undertaken to examine the relationship between PCI procedural volume (both at hospital- and operator-levels) and outcomes in adults. The primary outcome was mortality. The secondary outcomes were complications, healthcare utilisation and process outcomes. Searches were conducted from 1 January 2008 to 28 May 2019. Certainty of the evidence was assessed using 'Grading of Recommendations, Assessment, Development and Evaluations' (GRADE). Screening, data extraction, quality appraisal and GRADE assessments were conducted independently by two reviewers. RESULTS: Of 1,154 unique records retrieved, 22 observational studies with 6,432,265 patients were included. No significant association was found between total PCI hospital volume and mortality (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.69-1.03, I 2 = 86%). A temporal trend from significant to non-significant pooled effect estimates was observed. The pooled effect estimate for mortality was found to be significantly in favour of high-volume operators for total PCI procedures (OR: 0.77, 95% CI: 0.63-0.94, I 2 = 93%), and for high-volume hospitals for primary PCI procedures (OR: 0.77, 95% CI: 0.62-0.94, I 2 = 78%). Overall, GRADE certainty of evidence was 'very low'. There were mixed findings for secondary outcomes. CONCLUSIONS: A volume-outcome relationship may exist in certain situations, although this relationship appears to be attenuating with time, and there is 'very low' certainty of evidence. While volume might be important, it should not be the only standard used to define an acceptable PCI service and a broader evaluation of quality metrics should be considered that encompass patient experience and clinical outcomes. Systematic review registration: PROSPERO, CRD42019125288.

Identifying behavior change techniques for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia.

Nursing home residents with dementia are commonly prescribed antipsychotics despite the associated increased risk of harms. Interventions to optimize prescribing practice have been found to be effective in the short term, but there is a lack of evidence to support sustainability of effects, along with a lack of theory, public involvement, and transparency in the intervention development process. Using theory has been advocated as a means of improving intervention sustainability. The aim of this study was, therefore, to identify behavior change techniques (BCTs) for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia. A comprehensive approach to identifying a long list of all potential BCTs from three different sources was undertaken. The most appropriate BCTs were then selected through a two-round Delphi consensus survey with a broad range of experts (n = 18 panelists). Advisory groups of people with dementia, family carers, and professional stakeholders provided feedback on the final BCTs included. After two Delphi survey rounds, agreement was reached on 22 BCTs. Further refinement of the selected BCTs based on advisory group and panelists' feedback, along with use of the APEASE criteria (Affordability, Practicability, Effectiveness, Acceptability, Side effects/safety, and Equity) resulted in a final list of 16 BCTs. The next step in intervention development will be to identify the most appropriate mode of delivery of the 16 BCTs identified for inclusion. The study provides a case example of a systematic approach to incorporating evidence with stakeholder views in the identification of appropriate BCTs.

Immune response following infection with SARS-CoV-2 and other coronaviruses: A rapid review.

In this review, we systematically searched and summarized the evidence on the immune response and reinfection rate following SARS-CoV-2 infection. We also retrieved studies on SARS-CoV and MERS-CoV to assess the long-term duration of antibody responses. A protocol based on Cochrane rapid review methodology was adhered to and databases were searched from 1/1/2000 until 26/5/2020. Of 4744 citations retrieved, 102 studies met our inclusion criteria. Seventy-four studies were retrieved on SARS-CoV-2. While the rate and timing of IgM and IgG seroconversion were inconsistent across studies, most seroconverted for IgG within 2 weeks and 100% (N = 62) within 4 weeks. IgG was still detected at the end of follow-up (49-65 days) in all patients (N = 24). Neutralizing antibodies were detected in 92%-100% of patients (up to 53 days). It is not clear if reinfection with SARS-CoV-2 is possible, with studies more suggestive of intermittent detection of residual RNA. Twenty-five studies were retrieved on SARS-CoV. In general, SARS-CoV-specific IgG was maintained for 1-2 years post-infection and declined thereafter, although one study detected IgG up to 12 years post-infection. Neutralizing antibodies were detected up to 17 years in another study. Three studies on MERS-CoV reported that IgG may be detected up to 2 years. In conclusion, limited early data suggest that most patients seroconvert for SARS-CoV-2-specific IgG within 2 weeks. While the long-term duration of antibody responses is unknown, evidence from SARS-CoV studies suggest SARS-CoV-specific IgG is sustained for 1-2 years and declines thereafter.

Airborne transmission of SARS-CoV-2 via aerosols.

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.

Alternative clinical specimens for the detection of SARS-CoV-2: A rapid review.

The collection of nasopharyngeal swabs to test for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an invasive technique with implications for patients and clinicians. Alternative clinical specimens from the upper respiratory tract may offer benefits in terms of collection, comfort and infection risk. The objective of this review was to synthesise the evidence for detection of SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) tested saliva or nasal specimens compared with RT-PCR tested nasopharyngeal specimens. Searches were conducted in PubMed, Embase, Europe PMC and NHS evidence from December 2019 to 20 July 2020. Eighteen studies were identified; 12 for saliva, four for nasal and two included both specimen types. For saliva-based studies, the proportion of saliva samples testing positive relative to all positive samples in each study ranged from 82.9% to 100%; detection in nasopharyngeal specimens ranged from 76.7% to 100%; positive agreement between specimens for overall detection ranged from 65.4% to 100%. For nasal-based studies, the proportion of nasal swabs testing positive relative to all positive samples in each study ranged from 81.9% to 100%; detection in nasopharyngeal specimens ranged from 70% to 100%; positive agreement between specimens for overall detection ranged from 62.3% to 100%. The results indicate an inconsistency in the detection of SARS-CoV-2 RNA in the specimen types included, often with neither the index nor the reference of interest detecting all known cases. Depending on the test environment, these clinical specimens may offer a viable alternative to standard. However, at present the evidence is limited, of variable quality, and relatively inconsistent.

The duration of infectiousness of individuals infected with SARS-CoV-2.

OBJECTIVES: To summarise the evidence on the duration of infectiousness of individuals in whom SARS-CoV-2 ribonucleic acid is detected. METHODS: A rapid review was undertaken in PubMed, Europe PubMed Central and EMBASE from 1 January 2020 to 26 August 2020. RESULTS: We identified 15 relevant studies, including 13 virus culture and 2 contact tracing studies. For 5 virus culture studies, the last day on which SARS-CoV-2 was isolated occurred within 10 days of symptom onset. For another 5 studies, SARS-CoV-2 was isolated beyond day 10 for approximately 3% of included patients. The remaining 3 virus culture studies included patients with severe or critical disease; SARS-CoV-2 was isolated up to day 32 in one study. Two studies identified immunocompromised patients from whom SARS-CoV-2 was isolated for up to 20 days. Both contact tracing studies, when close contacts were first exposed greater than 5 days after symptom onset in the index case, found no evidence of laboratory-confirmed onward transmission of SARS-CoV-2. CONCLUSION: COVID-19 patients with mild-to-moderate illness are highly unlikely to be infectious beyond 10 days of symptoms. However, evidence from a limited number of studies indicates that patients with severe-to-critical illness or who are immunocompromised, may shed infectious virus for longer.

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases.

OBJECTIVES: Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach. DESIGN: Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics. INFORMATION SOURCES: Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases. RESULTS: There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5-9.5 days. Median presymptomatic infectious period across studies varied over <1-4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data. CONCLUSIONS: There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.