Explore the vast range of titles available.

School-based COVID-19 contacts in England have been asked to self-isolate at home, missing key educational opportunities. We trialled daily testing of contacts as an alternative to assess whether this resulted in similar control of transmission, while allowing more school attendance. We did an open-label, cluster-randomised, controlled trial in secondary schools and further education colleges in England. Schools were randomly assigned (1:1) to self-isolation of school-based COVID-19 contacts for 10 days (control) or to voluntary daily lateral flow device (LFD) testing for 7 days with LFD-negative contacts remaining at school (intervention). Randomisation was stratified according to school type and size, presence of a sixth form, presence of residential students, and proportion of students eligible for free school meals. Group assignment was not masked during procedures or analysis. Coprimary outcomes in all students and staff were COVID-19-related school absence and symptomatic PCR-confirmed COVID-19, adjusted for community case rates, to estimate within-school transmission (non-inferiority margin <50% relative increase). Analyses were done on an intention-to-treat basis using quasi-Poisson regression, also estimating complier average causal effects (CACE). This trial is registered with the ISRCTN registry, ISRCTN18100261. Between March 18 and May 4, 2021, 204 schools were taken through the consent process, during which three decided not to participate further. 201 schools were randomly assigned (control group n=99, intervention group n=102) in the 10-week study (April 19–May 10, 2021), which continued until the pre-appointed stop date (June 27, 2021). 76 control group schools and 86 intervention group schools actively participated; additional national data allowed most non-participating schools to be included in analysis of coprimary outcomes. 2432 (42·4%) of 5763 intervention group contacts participated in daily contact testing. There were 657 symptomatic PCR-confirmed infections during 7 782 537 days-at-risk (59·1 per 100 000 per week) in the control group and 740 during 8 379 749 days-at-risk (61·8 per 100 000 per week) in the intervention group (intention-to-treat adjusted incidence rate ratio [aIRR] 0·96 [95% CI 0·75–1·22]; p=0·72; CACE aIRR 0·86 [0·55–1·34]). Among students and staff, there were 59 422 (1·62%) COVID-19-related absences during 3 659 017 person-school-days in the control group and 51 541 (1·34%) during 3 845 208 person-school-days in the intervention group (intention-to-treat aIRR 0·80 [95% CI 0·54–1·19]; p=0·27; CACE aIRR 0·61 [0·30–1·23]). Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures. UK Government Department of Health and Social Care.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large. This Review highlights the progress that has been made in the development of diagnostic tools for the detection of SARS-CoV-2 in the fight against COVID-19.

As one of the major approaches in combating the COVID-19 pandemics, the availability of specific and reliable assays for the SARS-CoV-2 viral genome and its proteins is essential to identify the infection in suspected populations, make diagnoses in symptomatic or asymptomatic individuals, and determine clearance of the virus after the infection. For these purposes, use of the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for detection of the viral nucleic acid remains the most valuable in terms of its specificity, fast turn-around, high-throughput capacity, and reliability. It is critical to update the sequences of primers and probes to ensure the detection of newly emerged variants. Various assays for increased levels of IgG or IgM antibodies are available for detecting ongoing or past infection, vaccination responses, and persistence and for identifying high titers of neutralizing antibodies in recovered individuals. Viral genome sequencing is increasingly used for tracing infectious sources, monitoring mutations, and subtype classification and is less valuable in diagnosis because of its capacity and high cost. Nanopore target sequencing with portable options is available for a quick process for sequencing data. Emerging CRISPR-Cas-based assays, such as SHERLOCK and AIOD-CRISPR, for viral genome detection may offer options for prompt and point-of-care detection. Moreover, aptamer-based probes may be multifaceted for developing portable and high-throughput assays with fluorescent or chemiluminescent probes for viral proteins. In conclusion, assays are available for viral genome and protein detection, and the selection of specific assays depends on the purposes of prevention, diagnosis and pandemic control, or monitoring of vaccination efficacy. During the COVID-19 pandemics, sensitive and reliable assays for SARS-CoV-2 detection are essential for screening the population, identifying asymptomatic individuals, making diagnoses, monitoring treatment responses, and determining viral clearance. This review summarizes the principles, advantages, disadvantages, and specific applications of currently available assays for detection of the viral nucleotide, genome or proteins, as well as host antibody responses, and provide overall guidelines for selection of optimal assays for specific usage.

A versatile portfolio of diagnostic tests is essential for the containment of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Besides nucleic acid-based test systems and point-of-care (POCT) antigen (Ag) tests, quantitative, laboratory-based nucleocapsid Ag tests for SARS-CoV-2 have recently been launched. Here, we evaluated four commercial Ag tests on automated platforms and one POCT to detect SARS-CoV-2. We evaluated PCR-positive ( n  = 107) and PCR-negative ( n  = 303) respiratory swabs from asymptomatic and symptomatic patients at the end of the second pandemic wave in Germany (February–March 2021) as well as clinical isolates EU1 (B.1.117), variant of concern (VOC) Alpha (B.1.1.7) or Beta (B.1.351), which had been expanded in a biosafety level 3 laboratory. The specificities of automated SARS-CoV-2 Ag tests ranged between 97.0 and 99.7% (Lumipulse G SARS-CoV-2 Ag (Fujirebio): 97.03%, Elecsys SARS-CoV-2 Ag (Roche Diagnostics): 97.69%; LIAISON ® SARS-CoV-2 Ag (Diasorin) and SARS-CoV-2 Ag ELISA (Euroimmun): 99.67%). In this study cohort of hospitalized patients, the clinical sensitivities of tests were low, ranging from 17.76 to 52.34%, and analytical sensitivities ranged from 420,000 to 25,000,000 Geq/ml. In comparison, the detection limit of the Roche Rapid Ag Test (RAT) was 9,300,000 Geq/ml, detecting 23.58% of respiratory samples. Receiver-operating-characteristics (ROCs) and Youden’s index analyses were performed to further characterize the assays’ overall performance and determine optimal assay cutoffs for sensitivity and specificity. VOCs carrying up to four amino acid mutations in nucleocapsid were detected by all five assays with characteristics comparable to non-VOCs. In summary, automated, quantitative SARS-CoV-2 Ag tests show variable performance and are not necessarily superior to a standard POCT. The efficacy of any alternative testing strategies to complement nucleic acid-based assays must be carefully evaluated by independent laboratories prior to widespread implementation.

Testing for SARS-CoV-2 is essential to provide early COVID-19 treatment for people at high risk of severe illness and to limit the spread of infection in society. Proper upper respiratory specimen collection is the most critical step in the diagnosis of the SARS-CoV-2 virus in public settings, and throat swabs were the preferred specimens used for mass testing in many countries during the COVID-19 pandemic. However, there is still a discussion about whether throat swabs have a high enough sensitivity for SARS-CoV-2 diagnostic testing, as previous studies have reported a large variability in the sensitivity from 52% to 100%. Many previous studies exploring the diagnostic accuracy of throat swabs lack a detailed description of the sampling technique, which makes it difficult to compare the different diagnostic accuracy results. Some studies perform a throat swab by only collecting specimens from the posterior oropharyngeal wall, while others also include a swab of the palatine tonsils for SARS-CoV-2 testing. However, studies suggest that the palatine tonsils could have a tissue tropism for SARS-CoV-2 that may improve the SARS-CoV-2 detection during sampling. This may explain the variation of sensitivity reported, but no clinical studies have yet explored the differences in sensitivity and patient discomfort whether the palatine tonsils are included during the throat swab or not. The objective of this study is to examine the sensitivity and patient discomfort of a throat swab including the palatine tonsils compared to only swabbing the posterior oropharyngeal wall in molecular testing for SARS-CoV-2. We will conduct a randomized controlled study to compare the molecular detection rate of SARS-CoV-2 by a throat swab performed from the posterior oropharyngeal wall and the palatine tonsils (intervention group) or the posterior oropharyngeal wall only (control group). Participants will be randomized in a 1:1 ratio. All participants fill out a baseline questionnaire upon enrollment in the trial, examining their reason for being tested, symptoms, and previous tonsillectomy. A follow-up questionnaire will be sent to participants to explore the development of symptoms after testing. A total of 2315 participants were enrolled in this study between November 10, 2022, and December 22, 2022. The results from the follow-up questionnaire are expected to be completed at the beginning of 2024. This randomized clinical trial will provide us with information about whether throat swabs including specimens from the palatine tonsils will improve the diagnostic sensitivity for SARS-CoV-2 molecular detection. These results can, therefore, be used to improve future testing recommendations and provide additional information about tissue tropism for SARS-CoV-2. ClinicalTrials.gov NCT05611203; https://clinicaltrials.gov/study/NCT05611203. DERR1-10.2196/47446.

Scientists still debate whether millions of cheap, fast diagnostic kits will help control the pandemic. Here’s why. Scientists still debate whether millions of cheap, fast diagnostic kits will help control the pandemic. Here’s why.

Background Providing non-invasive, accurate and affordable SARS-CoV-2 tests represents a public health priority, to better control the spread of the virus while protecting healthcare workers. Saliva is a robust alternative to nasopharyngeal (NP) swabs, but there is heterogeneity in collection and pre-analytical methods. Methods Relying on a national COVID-19 Public Health Programme, we prospectively recruited 3,488 symptomatic and asymptomatic adults attending the Monaco community centre for NP RT-PCR testing from February 2021–2023. Saliva was concomitantly obtained with either a buccal swab or an oral sponge (OS) and analysed by an RT-PCR assay and a fully automated electrochemiluminescence enzyme immunoassay (ECLIA) rapid antigen test (RAT). Results The sensitivity of the buccal RT-PCR varied according to previous SARS-CoV-2 infection, vaccination, and the presence of symptoms, while it remained around 95% for the OS RT-PCR. The specificity of the buccal RT-PCR approached 100% and was around 95% for the OS-RT PCR. The RAT sensitivity was 66.9% and 69.1% compared to NP and OS RT-PCR assays and increased to 71% and 97% in case of a high viral load (Ct < 25), respectively. Conclusions RT-PCR assay using OS saliva showed high accuracy in symptomatic and non-symptomatic adults, including the identification of negative nasopharyngeal swabs. This method allows self-collection without any prior conditions for the patient nor laboratory pre-analytical steps. The ECLIA RAT offers high throughput but is only useful in individuals with high viral loads. Our findings encompassed the latest SARS-CoV-2 omicron subvariants, such as BA.4&5 and the XBB series. Trial registration Registry: ClinicalTrials.gov. Registration number: NCT05074745. Registration date: 12-10-2021.

Non-pharmaceutical interventions were used widely in care homes for older people during the COVID-19 pandemic, but there have been few randomised trials to support policy decisions. We aimed to evaluate the effect of biweekly asymptomatic staff testing with support funding for sick pay and agency staffing on the clinical outcomes of residents. We conducted a cluster randomised unblinded superiority trial, aiming to recruit up to 280 residential and/or nursing homes in England providing care to adults aged >65 years. Homes were randomised 1:1 to the control arm, which followed national testing policy (comprising symptomatic plus outbreak testing at trial initiation) or intervention (additional twice weekly asymptomatic staff testing for SARS-CoV-2, staff sick pay and agency backfill). Outcomes were evaluated using health data from routine national datasets in combination with aggregate data from participating homes. The primary outcome was the incidence of COVID-19-related hospital admissions in residents. The trial was conducted from January to August 2023, with 41 care homes randomised to intervention and 40 randomised to control included in the analysis. The trial was stopped early as it was not adequately powered for the primary outcome due to site recruitment and primary outcome events being substantially lower than expected. There was no significant difference in the primary outcome of resident COVID-linked hospital admission incidence between intervention and control arms (22.7/1000 person-years vs 15.0/1000 person-years, incidence rate ratio 1.19, 95%CI 0.55-2.58, P = 0.66; incidence rate difference 4.0, 95%CI -14.3 to 22.2). Trial set up took less than three months. Most trial outcomes were derived from routinely collected data. Recorded uptake of staff testing in the intervention arm was low (mean per home each week 14.4%). This trial was not well-powered to evaluate the impact of the intervention on the primary outcome, and recorded uptake of staff testing was low. However, our pre-existing care home network underpinned by linked routinely collected data provides a model for more agile interventional studies in the care home setting. NCT05639205.

With the ongoing COVID-19 (Coronavirus Disease 2019) pandemic, caused by the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), there is a need for sensitive, specific, and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR (quantitative reverse transcription PCR), with many commercial kits now available for this purpose. However, these are expensive, and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside a human cellular control ( RPP30 ) and a viral spike-in control (Phocine Herpes Virus 1 [PhHV-1]), which monitor sample quality and nucleic acid extraction efficiency, respectively. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by combined nose and throat swabbing and establish a statistically significant correlation between the detected level of human and SARS-CoV-2 nucleic acids. The inclusion of the human control probe in our assay therefore provides a quantitative measure of sample quality that could help reduce false-negative rates. We demonstrate the feasibility of establishing a robust RT-qPCR assay at approximately 10% of the cost of equivalent commercial assays, which could benefit low-resource environments and make high-volume testing affordable.

SARS-CoV-2 is the novel coronavirus that causes COVID-19. The spectrum of asymptomatic, presymptomatic, and symptomatic SARS-CoV-2 transmission presents challenges for evaluating SARS-CoV-2 test performance for diagnostic or screening purposes and for interpreting test results. Molecular and antigen tests can detect current SARS-CoV-2 infection and are used to diagnose COVID-19. Clinicians should consider a test's characteristics, test timing in relation to symptom onset, and the pretest probability of disease when interpreting results. Molecular and antigen SARS-CoV-2 tests both have high specificity. However, antigen tests generally have lower sensitivity and thus greater potential for false-negative results. Pretest probability of disease should be based on a patient's exposure to someone with a confirmed or probable case, signs or symptoms of COVID-19, local or population-specific COVID-19 prevalence, and presence of an alternative diagnosis. Using a leaf plot is an efficient way to visualize posttest probability of disease based on estimated pretest probability and the test's sensitivity and specificity. A negative molecular or antigen test result might not rule out SARS-CoV-2 infection when pretest probability is high, depending on the test's sensitivity. A symptom-based approach is preferred over a test-based approach for discontinuing isolation precautions for most patients with COVID-19 because prolonged shedding of viral RNA does not necessarily correlate with infectivity. Antibody tests might help identify past SARS-CoV-2 infection if performed two to four weeks after symptom onset; however, because of uncertainty about the extent and durability of postinfection or vaccine-induced immunity, they should not yet be used to infer immunity or guide discontinuation of personal protective measures.