Objectives: To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity. Methods: A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020. Results: We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance. No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus. Conclusion: There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
Summary 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.
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
Summary Despite over 140 million SARS‐CoV‐2 infections worldwide since the beginning of the pandemic, relatively few confirmed cases of SARS‐CoV‐2 reinfection have been reported. While immunity from SARS‐CoV‐2 infection is probable, at least in the short term, few studies have quantified the reinfection risk. To our knowledge, this is the first systematic review to synthesise the evidence on the risk of SARS‐CoV‐2 reinfection over time. A standardised protocol was employed, based on Cochrane methodology. Electronic databases and preprint servers were searched from 1 January 2020 to 19 February 2021. Eleven large cohort studies were identified that estimated the risk of SARS‐CoV‐2 reinfection over time, including three that enrolled healthcare workers and two that enrolled residents and staff of elderly care homes. Across studies, the total number of PCR‐positive or antibody‐positive participants at baseline was 615,777, and the maximum duration of follow‐up was more than 10 months in three studies. Reinfection was an uncommon event (absolute rate 0%–1.1%), with no study reporting an increase in the risk of reinfection over time. Only one study estimated the population‐level risk of reinfection based on whole genome sequencing in a subset of patients; the estimated risk was low (0.1% [95% CI: 0.08–0.11%]) with no evidence of waning immunity for up to 7 months following primary infection. These data suggest that naturally acquired SARS‐CoV‐2 immunity does not wane for at least 10 months post‐infection. However, the applicability of these studies to new variants or to vaccine‐induced immunity remains uncertain.
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.
Aim To systematically identify and appraise the international literature on the cost-effectiveness of metabolic surgery for the treatment of comorbid type 2 diabetes (T2D) and obesity. Methods A systematic search was conducted in electronic databases and grey literature sources up to 20 January 2021. Economic evaluations in a T2D population or a subpopulation with T2D were eligible for inclusion. Screening, data extraction, critical appraisal of methodological quality (Consensus Health Economic Criteria list) and assessment of transferability (International Society for Pharmacoeconomics and Outcomes Research questionnaire) were undertaken in duplicate. The incremental cost-effectiveness ratio (ICER) was the main outcome. Costs were reported in 2020 Irish Euro. Cost-effectiveness was interpreted using willingness-to-pay (WTP) thresholds of €20,000 and €45,000/quality-adjusted life year (QALY). Due to heterogeneity arising from various sources, a narrative synthesis was undertaken. Results Thirty studies across seventeen jurisdictions met the inclusion criteria; 16 specifically in a T2D population and 14 in a subpopulation with T2D. Overall, metabolic surgery was found to be cost-effective or cost-saving. Where undertaken, the results were robust to sensitivity and scenario analyses. Of the 30 studies included, 15 were considered high quality. Identified limitations included limited long-term follow-up data and uncertainty regarding the utility associated with T2D remission. Conclusion Published high-quality studies suggest metabolic surgery is a cost-effective or cost-saving intervention. As the prevalence of obesity and obesity-related diseases increases worldwide, significant investment and careful consideration of the resource requirements needed for metabolic surgery programmes will be necessary to ensure that service provision is adequate to meet demand.
The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratorybased anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I 2 = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I 2 = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I 2 = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.
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