ABSTRACT
Countries around the world have implemented restrictions on mobility, especially cross-border travel to reduce or prevent SARS-CoV-2 community transmission. Rapid antigen testing (Ag-RDT), with on-site administration and rapid turnaround time may provide a valuable screening measure to ease cross-border travel while minimizing risk of local transmission. To maximize impact, we developed an optimal Ag-RDT screening algorithm for cross-border entry. Using a previously developed mathematical model, we determined the daily number of imported COVID-19 cases that would generate no more than a relative 1% increase in cases over one month for different effective reproductive numbers (Rt) and COVID-19 prevalence within the recipient country. We then developed an algorithm—for differing levels of Rt, arrivals per day, mode of travel, and SARS-CoV-2 prevalence amongst travelers—to determine the minimum proportion of people that would need Ag-RDT testing at border crossings to ensure no greater than the relative 1% community spread increase. When daily international arrivals and/or COVID-19 prevalence amongst arrivals increases, the proportion of arrivals required to test using Ag-RDT increases. At very high numbers of international arrivals/COVID-19 prevalence, Ag-RDT testing is not sufficient to prevent increased community spread, especially when recipient country prevalence and Rt are low. In these cases, Ag-RDT screening would need to be supplemented with other measures to prevent an increase in community transmission. An efficient Ag-RDT algorithm for SARS-CoV-2 testing depends strongly on the epidemic status within the recipient country, volume of travel, proportion of land and air arrivals, test sensitivity, and COVID-19 prevalence among travelers.
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The first step in SARS-CoV-2 genomic surveillance is testing to identify people who are infected. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (mean = 27 tests per 100,000 people per day). We simulated COVID-19 epidemics in a prototypical low- and middle-income country to investigate how testing rates, sampling strategies and sequencing proportions jointly impact surveillance outcomes, and showed that low testing rates and spatiotemporal biases delay time to detection of new variants by weeks to months and can lead to unreliable estimates of variant prevalence, even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of approximately 100 tests per 100,000 people per day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.
Subject(s)
COVID-19 , Epidemics , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/genetics , Genomics , Diagnostic Techniques and Procedures , COVID-19 TestingABSTRACT
INTRODUCTION: Patients with post-COVID-19 syndrome may present cognitive and emotional symptomatology. This study aims to analyse the results of an outpatient neuropsychological intervention program for post-COVID-19 syndrome. METHOD: In June 2020 Institut Guttmann started an outpatient post-COVID-19 neurorehabilitation program, including respiratory therapy, physiotherapy, and neuropsychological rehabilitation. Before and after the program, the cognitive-emotional state of all participants is assessed. Six months after treatment, a follow-up assessment is administered (which includes a collection of information on various aspects of daily life). RESULTS: The sample analysed consisted of 123 patients (mean age: 51 years, SD: 12.41). Seventy-four per cent (n=91) had cognitive impairment and underwent cognitive treatment (experimental group); the remaining 26% (n=32) constituted the control group. After the intervention, the experimental group improved in working memory, verbal memory (learning, recall and recognition), verbal fluency and anxious-depressive symptomatology. The control group showed changes in immediate memory, verbal memory (learning and recognition) and depressive symptomatology, although the effect size in the latter two was smaller than in the experimental group. Six months after treatment, 44.9% of the patients were unable to perform their pre-COVID-19 work activity, and 81.2% reported difficulties in their activities of daily living. CONCLUSIONS: Neuropsychological rehabilitation is an effective tool to treat the cognitive-emotional deficits present in post-COVID-19 syndrome. However, months after the end of treatment, not all patients recover their pre-COVID-19 functional level.
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Introducción: Las personas con síndrome post-COVID-19 pueden presentar sintomatología cognitiva y emocional. Este estudio tiene como objetivo analizar los resultados de un programa ambulatorio de intervención neuropsicológica dirigido a pacientes con síndrome post-COVID-19. Método: En junio de 2020 Institut Guttmann inicia un programa ambulatorio de neurorrehabilitación post-COVID-19, que incluye terapia respiratoria, fisioterapia y rehabilitación neuropsicológica. Antes y después del programa se valora el estado cognitivo-emocional de todos los participantes. Seis meses después del tratamiento se administra una valoración de seguimiento (en la que se recoge información sobre diversos aspectos de la vida diaria). Resultados: La muestra analizada estaba formada por 123 pacientes (edad media: 51 años, DS: 12,41). El 74% (n=91) presentaba alteraciones cognitivas y realizó tratamiento cognitivo (grupo experimental);el 26% (n=32) restante constituyó el grupo control. Tras la intervención, el grupo experimental mejoró en memoria de trabajo, memoria verbal (aprendizaje, recuerdo y reconocimiento), fluencia verbal y sintomatología ansioso-depresiva. El grupo control mostró cambios en memoria inmediata, memoria verbal (aprendizaje y reconocimiento) y sintomatología depresiva, si bien el tamaño del efecto en las dos últimas fue menor que en el grupo experimental. Seis meses después del tratamiento, el 44,9% de los pacientes no podía realizar la actividad laboral previa al COVID-19. El 81,2% refirió dificultades en sus actividades de la vida diaria. Conclusiones: La rehabilitación neuropsicológica es una herramienta eficaz para tratar las alteraciones cognitivo-emocionales presentes en el síndrome post-COVID-19. Sin embargo, meses después de finalizar el tratamiento, no todos los pacientes recuperan el nivel funcional pre-COVID-19.
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Although COVID-19 vaccines are globally available, waning immunity and emerging vaccine-evasive variants of concern have hindered the international response and transition to a post-pandemic era. Testing to identify and isolate infectious individuals remains the most proactive strategy for containing an ongoing COVID-19 outbreak. We developed a stochastic, compartmentalized model to simulate the impact of using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) assays, rapid antigen tests, and vaccinations on SARS-CoV-2 spread. We compare testing strategies across an example high-income country (the United States) and low- and middle-income country (India). We detail the optimal testing frequency and coverage in the US and India to mitigate an emerging outbreak even in a vaccinated population: overall, maximizing testing frequency is most important, but having high testing coverage remains necessary when there is sustained transmission. A resource-limited vaccination strategy still requires high-frequency testing to minimize subsequent outbreaks and is 16.50% more effective in reducing cases in India than the United States. Tailoring testing strategies to transmission settings can help effectively reduce disease burden more than if a uniform approach were employed without regard to epidemiological variability across locations.
Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines , Disease Outbreaks/prevention & control , Humans , United States/epidemiologyABSTRACT
Countries around the world have implemented restrictions on mobility, especially cross-border travel to reduce or prevent SARS-CoV-2 community transmission. Rapid antigen testing (Ag-RDT), with on-site administration and rapid turnaround time may provide a valuable screening measure to ease cross-border travel while minimizing risk of local transmission. To maximize impact, we developed an optimal Ag-RDT screening algorithm for cross-border entry. Using a previously developed mathematical model, we determined the daily number of imported COVID-19 cases that would generate no more than a relative 1% increase in cases over one month for different effective reproductive numbers (Rt) and COVID-19 prevalence within the recipient country. We then developed an algorithm-for differing levels of Rt, arrivals per day, mode of travel, and SARS-CoV-2 prevalence amongst travelers-to determine the minimum proportion of people that would need Ag-RDT testing at border crossings to ensure no greater than the relative 1% community spread increase. When daily international arrivals and/or COVID-19 prevalence amongst arrivals increases, the proportion of arrivals required to test using Ag-RDT increases. At very high numbers of international arrivals/COVID-19 prevalence, Ag-RDT testing is not sufficient to prevent increased community spread, especially when recipient country prevalence and Rt are low. In these cases, Ag-RDT screening would need to be supplemented with other measures to prevent an increase in community transmission. An efficient Ag-RDT algorithm for SARS-CoV-2 testing depends strongly on the epidemic status within the recipient country, volume of travel, proportion of land and air arrivals, test sensitivity, and COVID-19 prevalence among travelers.
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BACKGROUND: Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. METHODS AND FINDINGS: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched preprint and peer-reviewed databases for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariable mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1). When manufacturer instructions were followed, sensitivity increased to 76.3% (95% CI 73.7 to 78.7). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values ≥25 and ≥30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients' symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). Our analysis was limited by the included studies' heterogeneity in viral load assessment and sample origination. CONCLUSIONS: Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all (>90%) when high viral loads are present. With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.
Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Humans , Point-of-Care Systems , Sensitivity and SpecificityABSTRACT
A laboratory validation study was conducted to assess the equivalence of Xpert MTB/RIF Ultra testing on the GeneXpert System and the GeneXpert Omni System ('Omni') for tuberculosis and rifampicin resistance. High concordance of the two devices was demonstrated for well-characterized clinical samples as well as control materials, with controls tested on Omni at normal and challenging environmental conditions (i.e. 35°C, 90% relative humidity). Equivalence of the Cts for all probes was also shown. Equivalence was demonstrated for the Omni and GeneXpert devices for tuberculosis and rifampicin resistance detection for a diverse range of clinical specimens and environmental conditions.
Subject(s)
Antibiotics, Antitubercular/pharmacology , Mycobacterium tuberculosis/drug effects , Point-of-Care Testing , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/diagnosis , Bacterial Proteins/genetics , DNA-Directed RNA Polymerases/genetics , Drug Resistance, Multiple, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Rifampin/pharmacology , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapyABSTRACT
"Fit-for-purpose" diagnostic tests have emerged as a prerequisite to achieving global targets for the prevention, control, elimination, and eradication of neglected tropical diseases (NTDs), as highlighted by the World Health Organization's (WHO) new roadmap. There is an urgent need for the development of new tools for those diseases for which no diagnostics currently exist and for improvement of existing diagnostics for the remaining diseases. Yet, efforts to achieve this, and other crosscutting ambitions, are fragmented, and the burden of these 20 debilitating diseases immense. Compounded by the Coronavirus Disease 2019 (COVID-19) pandemic, programmatic interruptions, systemic weaknesses, limited investment, and poor commercial viability undermine global efforts-with a lack of coordination between partners, leading to the duplication and potential waste of scant resources. Recognizing the pivotal role of diagnostic testing and the ambition of WHO, to move forward, we must create an ecosystem that prioritizes country-level action, collaboration, creativity, and commitment to new levels of visibility. Only then can we start to accelerate progress and make new gains that move the world closer to the end of NTDs.
Subject(s)
Neglected Diseases/prevention & control , Tropical Medicine , COVID-19/diagnosis , Disease Eradication , Humans , Neglected Diseases/diagnosis , SARS-CoV-2 , World Health OrganizationABSTRACT
BACKGROUND: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. METHODS AND FINDINGS: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting. CONCLUSIONS: In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.
Subject(s)
COVID-19 Serological Testing/methods , Age Factors , Antigens, Viral/analysis , COVID-19/diagnosis , COVID-19/etiology , COVID-19 Serological Testing/standards , Carrier State/diagnosis , Carrier State/virology , Humans , Nasopharynx/virology , Reagent Kits, Diagnostic , Reference Standards , SARS-CoV-2/immunology , Sensitivity and Specificity , Viral LoadABSTRACT
The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management.