The Clinical Severity of COVID-19 Variants of Concern: Retrospective Population-Based Analysis.

SARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs). This study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout. We used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs. We included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups. Our study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

Harrigan SP ，Velásquez García HA ，Abdia Y ，Wilton J ，Prystajecky N ，Tyson J ，Fjell C ，Hoang L ，Kwong JC ，Mishra S ，Wang L ，Sander B ，Janjua NZ ，Sbihi H ... -  《JMIR Public Health and Surveillance》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Workplace interventions to reduce the risk of SARS-CoV-2 infection outside of healthcare settings.

Although many people infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) experience no or mild symptoms, some individuals can develop severe illness and may die, particularly older people and those with underlying medical problems. Providing evidence-based interventions to prevent SARS-CoV-2 infection has become more urgent with the potential psychological toll imposed by the coronavirus disease 2019 (COVID-19) pandemic. Controlling exposures to occupational hazards is the fundamental method of protecting workers. When it comes to the transmission of viruses, workplaces should first consider control measures that can potentially have the most significant impact. According to the hierarchy of controls, one should first consider elimination (and substitution), then engineering controls, administrative controls, and lastly, personal protective equipment. This is the first update of a Cochrane review published 6 May 2022, with one new study added. To assess the benefits and harms of interventions in non-healthcare-related workplaces aimed at reducing the risk of SARS-CoV-2 infection compared to other interventions or no intervention. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science Core Collections, Cochrane COVID-19 Study Register, World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and medRxiv to 13 April 2023. We included randomised controlled trials (RCTs) and non-randomised studies of interventions. We included adult workers, both those who come into close contact with clients or customers (e.g. public-facing employees, such as cashiers or taxi drivers), and those who do not, but who could be infected by coworkers. We excluded studies involving healthcare workers. We included any intervention to prevent or reduce workers' exposure to SARS-CoV-2 in the workplace, defining categories of intervention according to the hierarchy of hazard controls (i.e. elimination; engineering controls; administrative controls; personal protective equipment). We used standard Cochrane methods. Our primary outcomes were incidence rate of SARS-CoV-2 infection (or other respiratory viruses), SARS-CoV-2-related mortality, adverse events, and absenteeism from work. Our secondary outcomes were all-cause mortality, quality of life, hospitalisation, and uptake, acceptability, or adherence to strategies. We used the Cochrane RoB 2 tool to assess risk of bias, and GRADE methods to evaluate the certainty of evidence for each outcome. We identified 2 studies including a total of 16,014 participants. Elimination-of-exposure interventions We included one study examining an intervention that focused on elimination of hazards, which was an open-label, cluster-randomised, non-inferiority trial, conducted in England in 2021. The study compared standard 10-day self-isolation after contact with an infected person to a new strategy of daily rapid antigen testing and staying at work if the test is negative (test-based attendance). The trialists hypothesised that this would lead to a similar rate of infections, but lower COVID-related absence. Staff (N = 11,798) working at 76 schools were assigned to standard isolation, and staff (N = 12,229) working at 86 schools were assigned to the test-based attendance strategy. The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of symptomatic polymerase chain reaction (PCR)-positive SARS-CoV-2 infection (rate ratio (RR) 1.28, 95% confidence interval (CI) 0.74 to 2.21; 1 study; very low-certainty evidence). The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of any PCR-positive SARS-CoV-2 infection (RR 1.35, 95% CI 0.82 to 2.21; 1 study; very low-certainty evidence). COVID-related absenteeism rates were 3704 absence days in 566,502 days-at-risk (6.5 per 1000 working days) in the control group and 2932 per 539,805 days-at-risk (5.4 per 1000 working days) in the intervention group (RR 0.83, 95% CI 0.55 to 1.25). We downgraded the certainty of the evidence to low due to imprecision. Uptake of the intervention was 71% in the intervention group, but not reported for the control intervention. The trial did not measure our other outcomes of SARS-CoV-2-related mortality, adverse events, all-cause mortality, quality of life, or hospitalisation. We found seven ongoing studies using elimination-of-hazard strategies, six RCTs and one non-randomised trial. Administrative control interventions We found one ongoing RCT that aims to evaluate the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in preventing COVID-19 infection and reducing disease severity. Combinations of eligible interventions We included one non-randomised study examining a combination of elimination of hazards, administrative controls, and personal protective equipment. The study was conducted in two large retail companies in Italy in 2020. The study compared a safety operating protocol, measurement of body temperature and oxygen saturation upon entry, and a SARS-CoV-2 test strategy with a minimum activity protocol. Both groups received protective equipment. All employees working at the companies during the study period were included: 1987 in the intervention company and 1798 in the control company. The study did not report an outcome of interest for this systematic review. Other intervention categories We did not find any studies in this category. We are uncertain whether a test-based attendance policy affects rates of PCR-positive SARS-CoV-2 infection (any infection; symptomatic infection) compared to standard 10-day self-isolation amongst school and college staff. A test-based attendance policy may result in little to no difference in absenteeism rates compared to standard 10-day self-isolation. The non-randomised study included in our updated search did not report any outcome of interest for this Cochrane review. As a large part of the population is exposed in the case of a pandemic, an apparently small relative effect that would not be worthwhile from the individual perspective may still affect many people, and thus become an important absolute effect from the enterprise or societal perspective. The included RCT did not report on any of our other primary outcomes (i.e. SARS-CoV-2-related mortality and adverse events). We identified no completed studies on any other interventions specified in this review; however, eight eligible studies are ongoing. More controlled studies are needed on testing and isolation strategies, and working from home, as these have important implications for work organisations.

Constantin AM ，Noertjojo K ，Sommer I ，Pizarro AB ，Persad E ，Durao S ，Nussbaumer-Streit B ，McElvenny DM ，Rhodes S ，Martin C ，Sampson O ，Jørgensen KJ ，Bruschettini M ... -  《Cochrane Database of Systematic Reviews》

The effect of sample site and collection procedure on identification of SARS-CoV-2 infection.

Sample collection is a key driver of accuracy in the diagnosis of SARS-CoV-2 infection. Viral load may vary at different anatomical sampling sites and accuracy may be compromised by difficulties obtaining specimens and the expertise of the person taking the sample. It is important to optimise sampling accuracy within cost, safety and accessibility constraints. To compare the sensitivity of different sampling collection sites and methods for the detection of current SARS-CoV-2 infection with any molecular or antigen-based test. Electronic searches of the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 22 February 2022. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions. We included studies of symptomatic or asymptomatic people with suspected SARS-CoV-2 infection undergoing testing. We included studies of any design that compared results from different sample types (anatomical location, operator, collection device) collected from the same participant within a 24-hour period. Within a sample pair, we defined a reference sample and an index sample collected from the same participant within the same clinical encounter (within 24 hours). Where the sample comparison was different anatomical sites, the reference standard was defined as a nasopharyngeal or combined naso/oropharyngeal sample collected into the same sample container and the index sample as the alternative anatomical site. Where the sample comparison was concerned with differences in the sample collection method from the same site, we defined the reference sample as that closest to standard practice for that sample type. Where the sample pair comparison was concerned with differences in personnel collecting the sample, the more skilled or experienced operator was considered the reference sample. Two review authors independently assessed the risk of bias and applicability concerns using the QUADAS-2 and QUADAS-C checklists, tailored to this review. We present estimates of the difference in the sensitivity (reference sample (%) minus index sample sensitivity (%)) in a pair and as an average across studies for each index sampling method using forest plots and tables. We examined heterogeneity between studies according to population (age, symptom status) and index sample (time post-symptom onset, operator expertise, use of transport medium) characteristics. This review includes 106 studies reporting 154 evaluations and 60,523 sample pair comparisons, of which 11,045 had SARS-CoV-2 infection. Ninety evaluations were of saliva samples, 37 nasal, seven oropharyngeal, six gargle, six oral and four combined nasal/oropharyngeal samples. Four evaluations were of the effect of operator expertise on the accuracy of three different sample types. The majority of included evaluations (146) used molecular tests, of which 140 used RT-PCR (reverse transcription polymerase chain reaction). Eight evaluations were of nasal samples used with Ag-RDTs (rapid antigen tests). The majority of studies were conducted in Europe (35/106, 33%) or the USA (27%) and conducted in dedicated COVID-19 testing clinics or in ambulatory hospital settings (53%). Targeted screening or contact tracing accounted for only 4% of evaluations. Where reported, the majority of evaluations were of adults (91/154, 59%), 28 (18%) were in mixed populations with only seven (4%) in children. The median prevalence of confirmed SARS-CoV-2 was 23% (interquartile (IQR) 13%-40%). Risk of bias and applicability assessment were hampered by poor reporting in 77% and 65% of included studies, respectively. Risk of bias was low across all domains in only 3% of evaluations due to inappropriate inclusion or exclusion criteria, unclear recruitment, lack of blinding, nonrandomised sampling order or differences in testing kit within a sample pair. Sixty-eight percent of evaluation cohorts were judged as being at high or unclear applicability concern either due to inflation of the prevalence of SARS-CoV-2 infection in study populations by selectively including individuals with confirmed PCR-positive samples or because there was insufficient detail to allow replication of sample collection. When used with RT-PCR • There was no evidence of a difference in sensitivity between gargle and nasopharyngeal samples (on average -1 percentage points, 95% CI -5 to +2, based on 6 evaluations, 2138 sample pairs, of which 389 had SARS-CoV-2). • There was no evidence of a difference in sensitivity between saliva collection from the deep throat and nasopharyngeal samples (on average +10 percentage points, 95% CI -1 to +21, based on 2192 sample pairs, of which 730 had SARS-CoV-2). • There was evidence that saliva collection using spitting, drooling or salivating was on average -12 percentage points less sensitive (95% CI -16 to -8, based on 27,253 sample pairs, of which 4636 had SARS-CoV-2) compared to nasopharyngeal samples. We did not find any evidence of a difference in the sensitivity of saliva collected using spitting, drooling or salivating (sensitivity difference: range from -13 percentage points (spit) to -21 percentage points (salivate)). • Nasal samples (anterior and mid-turbinate collection combined) were, on average, 12 percentage points less sensitive compared to nasopharyngeal samples (95% CI -17 to -7), based on 9291 sample pairs, of which 1485 had SARS-CoV-2. We did not find any evidence of a difference in sensitivity between nasal samples collected from the mid-turbinates (3942 sample pairs) or from the anterior nares (8272 sample pairs). • There was evidence that oropharyngeal samples were, on average, 17 percentage points less sensitive than nasopharyngeal samples (95% CI -29 to -5), based on seven evaluations, 2522 sample pairs, of which 511 had SARS-CoV-2. A much smaller volume of evidence was available for combined nasal/oropharyngeal samples and oral samples. Age, symptom status and use of transport media do not appear to affect the sensitivity of saliva samples and nasal samples. When used with Ag-RDTs • There was no evidence of a difference in sensitivity between nasal samples compared to nasopharyngeal samples (sensitivity, on average, 0 percentage points -0.2 to +0.2, based on 3688 sample pairs, of which 535 had SARS-CoV-2). When used with RT-PCR, there is no evidence for a difference in sensitivity of self-collected gargle or deep-throat saliva samples compared to nasopharyngeal samples collected by healthcare workers when used with RT-PCR. Use of these alternative, self-collected sample types has the potential to reduce cost and discomfort and improve the safety of sampling by reducing risk of transmission from aerosol spread which occurs as a result of coughing and gagging during the nasopharyngeal or oropharyngeal sample collection procedure. This may, in turn, improve access to and uptake of testing. Other types of saliva, nasal, oral and oropharyngeal samples are, on average, less sensitive compared to healthcare worker-collected nasopharyngeal samples, and it is unlikely that sensitivities of this magnitude would be acceptable for confirmation of SARS-CoV-2 infection with RT-PCR. When used with Ag-RDTs, there is no evidence of a difference in sensitivity between nasal samples and healthcare worker-collected nasopharyngeal samples for detecting SARS-CoV-2. The implications of this for self-testing are unclear as evaluations did not report whether nasal samples were self-collected or collected by healthcare workers. Further research is needed in asymptomatic individuals, children and in Ag-RDTs, and to investigate the effect of operator expertise on accuracy. Quality assessment of the evidence base underpinning these conclusions was restricted by poor reporting. There is a need for further high-quality studies, adhering to reporting standards for test accuracy studies.

Davenport C ，Arevalo-Rodriguez I ，Mateos-Haro M ，Berhane S ，Dinnes J ，Spijker R ，Buitrago-Garcia D ，Ciapponi A ，Takwoingi Y ，Deeks JJ ，Emperador D ，Leeflang MMG ，Van den Bruel A ，Cochrane COVID-19 Diagnostic Test Accuracy Group ... -  《Cochrane Database of Systematic Reviews》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》