Point-of-care testing for COVID-19: a simple two-step molecular diagnostic development and validation during the SARS-CoV-2 pandemic.

BACKGROUND: During the coronavirus disease 19 (COVID-19) pandemic, diagnostic testing of the general population proved challenging due to limitations of the gold-standard diagnostic procedure using reverse transcription real-time polymerase chain reaction (RT-qPCR) for large-scale testing on the centralised model, especially in low-resource areas. OBJECTIVES: To address this, a point-of-care (PoC) diagnostic protocol for COVID-19 was developed, providing fast, reliable, and affordable testing, particularly for low-mid develop areas. METHODS: The PoC diagnostic process combines a simple paper-based RNA extraction method housed within a 3D-printed plastic device with a colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. Nasopharyngeal/oropharyngeal swabs (NOS) and saliva samples were tested between 2020 and 2021, with the assistance of Santa Catarina's State Health Secretary, Brazil. FINDINGS: The developed diagnostic protocol showed a limit of detection of 9,900 copies and an overall diagnostic specificity of 98% for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1,348 clinical analysed samples. The diagnostic sensitivity was 95% for NOS samples, 85% for early morning saliva, and 69% for indiscriminate saliva. MAIN CONCLUSIONS: In conclusion, the developed device successfully extracted SARS-CoV-2 viral RNA from swabs and saliva clinical samples. When combined with colorimetric RT-LAMP, it provides results within 45 min using minimal resources, thus delivering a diagnostic kit protocol that is applicable in large-scale sampling.

Cost-effectiveness of SARS-CoV-2 self-testing at routine gatherings to minimize community-level infections in lower-middle income countries: A mathematical modeling study.

Places of worship serve as a venue for both mass and routine gathering around the world, and therefore are associated with risk of large-scale SARS-CoV-2 transmission. However, such routine gatherings also offer an opportunity to distribute self-tests to members of the community to potentially help mitigate transmission and reduce broader community spread of SARS-CoV-2. Over the past four years, self-testing strategies have been an impactful tool for countries' response to the COVID-19 pandemic, especially early on to mitigate the spread when vaccination and treatment options were limited. We used an agent-based mathematical model to estimate the impact of various strategies of symptomatic and asymptomatic self-testing for a fixed percentage of weekly routine gatherings at places of worship on community transmission of SARS-CoV-2 in Brazil, Georgia, and Zambia. Testing strategies assessed included weekly and bi-weekly self-testing across varying levels of vaccine effectiveness, vaccine coverage, and reproductive numbers to simulate developing stages of the COVID-19 pandemic. Self-testing symptomatic people attending routine gatherings can cost-effectively reduce the spread of SARS-CoV-2 within places of worship and the community, resulting in incremental cost-effectiveness ratios of $69-$303 USD. This trend is especially true in contexts where population level attendance at such gatherings is high, demonstrating that a distribution approach is more impactful when a greater proportion of the population is reached. Asymptomatic self-testing of attendees at 100% of places of worship in a country results in the greatest percent of infections averted and is consistently cost-effective but remains costly. Budgetary needs for asymptomatic testing are expensive and likely unaffordable for lower-middle income countries (520-1550x greater than that of symptomatic testing alone), promoting that strategies to strengthen symptomatic testing should remain a higher priority.

Cost-consequence analysis of a combined COVID-19/influenza rapid diagnostic test in the Brazilian private healthcare setting.

Combination COVID-19/influenza rapid tests provide a way to quickly and accurately differentiate between the two infections. The goal of this economic evaluation was to assess the cost and health benefits of a combination COVID-19/influenza Rapid Diagnostic Test (RDT) vs. current standard-of-care in the Brazilian private healthcare setting. A dual decision tree model was developed to estimate the impact of rapid differentiation of COVID-19 and influenza in a hypothetical cohort of 1,000 adults with influenza-like illness in an ambulatory healthcare setting. The model compared the use of a combination COVID-19/influenza RDT to Brazil standard diagnostic practice of a COVID-19 RDT and presumptive influenza diagnosis. Different levels of influenza prevalence were modeled with co-infection estimated as a function of the COVID-19 prevalence. Outcomes included accuracy of diagnosis, antiviral prescriptions and healthcare resource use (hospital bed days and ICU occupancy). Depending on influenza prevalence, considering 1,000 patients with influenza-like illness, a combination RDT compared to standard practice was estimated to result in between 88 and 149 fewer missed diagnoses of influenza (including co-infection), 161 to 185 fewer cases of over-diagnosis of influenza; a 24 to 34% reduction in hospital bed days and a 16 to 26% reduction in ICU days. In the base case scenario (20% influenza, 5% COVID-19), the combination RDT was estimated to result in cohort cost savings of $99. Based upon a de novo economic model, this analysis indicates that use of a combination RDT could positively impact influenza antiviral prescriptions and lower healthcare resource use.

Diagnostic Accuracy of the Abbott BinaxNOW COVID-19 Antigen Card Test, Puerto Rico.

BACKGROUND: The COVID-19 pandemic underscored the need for rapid and accurate diagnostic tools. In August 2020, the Abbott BinaxNOW COVID-19 Antigen Card test became available as a timely and affordable alternative for SARS-CoV-2 molecular testing, but its performance may vary due to factors including timing and symptomatology. This study evaluates BinaxNOW diagnostic performance in diverse epidemiological contexts. METHODS: Using RT-PCR as reference, we assessed performance of the BinaxNOW COVID-19 test for SARS-CoV-2 detection in anterior nasal swabs from participants of two studies in Puerto Rico from December 2020 to May 2023. Test performance was assessed by days post symptom onset, collection strategy, vaccination status, symptomatology, repeated testing, and RT-PCR cycle threshold (Ct) values. RESULTS: BinaxNOW demonstrated an overall sensitivity of 84.1% and specificity of 98.8%. Sensitivity peaked within 1-6 days after symptom onset (93.2%) and was higher for symptomatic (86.3%) than asymptomatic (67.3%) participants. Sensitivity declined over the course of infection, dropping from 96.3% in the initial test to 48.4% in testing performed 7-14 days later. BinaxNOW showed 99.5% sensitivity in participants with low Ct values (≤ 25) but lower sensitivity (18.2%) for participants with higher Cts (36-40). CONCLUSIONS: BinaxNOW demonstrated high sensitivity and specificity, particularly in early-stage infections and symptomatic participants. In situations where test sensitivity is crucial for clinical decision-making, nucleic acid amplification tests are preferred. These findings highlight the importance of considering clinical and epidemiological context when interpreting test results and emphasize the need for ongoing research to adapt testing strategies to emerging SARS-CoV-2 variants.

Implementation and Performance of a Point-of-Care COVID-19 Test Program in 4000 California Schools.

OBJECTIVE: To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments certificate of waiver, as well as training of school personnel. STUDY DESIGN: Descriptive report of a point-of-care, school-based antigen testing program in California from August 1st, 2021 through May 30, 2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944 009 students, personnel, and community members from 4022 California kindergarten through high schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator) of the Abbott BinaxNOW antigen test, number of tests performed, and active infections identified. RESULTS: Of 102 022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95% CI: 80.5%-81.8%) and 99.6% (95% CI: 99.5%-99.6%), respectively, using cycle threshold values <30. During January through March 2022, the highest prevalence period, the positive predictive value of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4022 school sites were enrolled and 3 987 840 million antigen tests were performed on 944 009 individuals. A total of 162 927 positive antigen tests were reported in 135 163 individuals (14.3% of persons tested). CONCLUSIONS: Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats.

Evaluation of self-collected nasal, urine, and saliva samples for molecular detection of SARS-CoV-2 using an EUA approved RT-PCR assay and a laboratory developed LAMP SARS-CoV-2 test.

As the SARS-CoV-2 virus spread throughout the world, millions of positive cases of COVID-19 were registered and, even though there are millions of people already vaccinated against SARS-CoV-2, a large part of the global population remains vulnerable to contracting the virus. Massive nasopharyngeal sample collection in Puerto Rico at the beginning of the pandemic was limited by the scarcity of trained personnel and testing sites. To increase SARS-CoV-2 molecular testing availability, we evaluated the diagnostic accuracy of self-collected nasal, saliva, and urine samples using the TaqPath reverse transcription polymerase chain reaction (RT-PCR) COVID-19 kit to detect SARS-CoV-2. We also created a colorimetric loop-mediated isothermal amplification (LAMP) laboratory developed test (LDT) to detect SARS-CoV-2, as another strategy to increase the availability of molecular testing in community-based laboratories. Automated RNA extraction was performed in the KingFisher Flex instrument, followed by PCR quantification of SARS-CoV-2 on the 7500 Fast Dx RT-PCR using the TaqPath RT-PCR COVID-19 molecular test. Data was interpreted by the COVID-19 Interpretive Software from Applied Biosystems and statistically analyzed with Cohen's kappa coefficient (k). Cohen's kappa coefficient (k) for paired nasal and saliva samples showed moderate agreement (0.52). Saliva samples exhibited a higher viral load. We also observed 90% concordance between LifeGene-Biomarks' SARS-CoV-2 Rapid Colorimetric LAMP LDT and the TaqPath RT-PCR COVID-19 test. Our results suggest that self-collected saliva is superior to nasal and urine samples for COVID-19 testing. The results also suggest that the colorimetric LAMP LDT is a rapid alternative to RT-PCR tests for the detection of SARS-CoV-2. This test can be easily implemented in clinics, hospitals, the workplace, and at home; optimizing the surveillance and collection process, which helps mitigate global public health and socioeconomic upheaval caused by airborne pandemics.

Original article: novelty of Canadian manufacture nasopharyngeal swabs for collection of samples being tested for SARS-CoV-2 in a pandemic setting.

Objectives: The COVID-19 pandemic caused a global shortage of nasopharyngeal (NP) swabs, required for RT-PCR testing. Canadian manufacturers were contacted to share NP swab innovations. The primary objective was to determine whether novel NP test swabs were comparable to commercially available swabs regarding user characteristics, ability to collect a specimen, and diagnostic performance using RT-PCR testing. Methods: Participants were randomized by swab (test/control) and nostril (left/right). A calculated positive percent agreement ≥90% was considered successful. Mean Ct values of viral genes and housekeeping gene (RNase P) were considered similar if a Ct difference ≤ 2 between control and test group was obtained. There also was a qualitative assessment of swabs usability. Results: 647 participants were enrolled from Huaycan Hospital in Lima, Peru, distributed over 8 NP swabs brands. Seven brands agreed to share their results. There were no statistically significant differences between the test swabs of these 7 brands and control swabs. Conclusion: All the seven brands are comparable to the commercially available flocked swabs used for SARS-CoV-2 regarding test results agreement, ability to collect a specimen, and user characteristics.

Caracterización epidemiológica de pacientes con COVID-19 en la Región Sanitaria de Francisco Morazán, Honduras / Epidemiological characterization of patients with COVID-19 in the Sanitary Region of Francisco Morazán, Honduras

Antecedentes: La infección por el virus SARS- CoV-2 causa la enfermedad por coronavirus 2019 ( COVID-19). Objetivo: Caracterizar epidemiológicamente al paciente con COVID-19, Región Sanitaria Departamental de Francisco Morazán (RSDFM), Honduras, marzo 2020-enero 2021. Métodos: Estudio descriptivo retrospectivo. Incluyó n=11,401 usuarios a quienes se les realizó confirmación diagnóstica en la RSDFM. Se calculó incidencia general y mensual de COVID-19 como tasas por 10,000 habitantes, tasas de incidencia municipal (casos positivos/10,000) y tasa de letalidad (fallecidos/100 casos positivos). Resultados: Del total de 3,680 usuarios, el promedio de edad de los casos positivos fue 36.8 años (DS+/-17.9); sexo femenino 53.3% (1,962), procedencia Valle de Ángeles 20.4% (752). El nexo epidemiológico fue contacto con familiar o amigo positivo o fallecido por COVID-19 en 96.3% (3,544). La tasa general de incidencia fue 92.4/10,000. El municipio de Valle de Ángeles presentó la tasa de incidencia más elevada 366.1/10,000. La tasa de letalidad fue 1.8% (68/3680). Discusión: Los hallazgos de este estudio son compatibles con otros autores con respecto a las características epidemiológicas y sintomatología, identificando mayor riesgo de mortalidad en los individuos con edad ≥60 años (35/418 vs <60 años 32/3194; p=0.000, OR: 8.60, IC95%: 5.15-14.37), así como para el sexo masculino (48/1670 vs 20/1942; p=0.000, OR:2.79, IC95%: 1.61- 4.89). Los meses de mayor incidencia de casos en la RSDFM fueron los meses de junio a julio del 2020 y diciembre del 2020 a enero del 2021. Estudios de este tipo fortalecen el abordaje epidemiológico de las epidemias/pandemias...(AU)

Uma análise dos principais diagnósticos de Sars-cov-2 disponíveis no Brasil: uma revisão de literatura / Diagnosis and main types of coronavirus in humans: a narrative review / Diagnóstico y principales tipos de coronavirus en humanos: una revisión narrativa

Introdução: Com a emergência do SARS-CoV-2 foi disponibilizado uma grande quantidade de ferramentas de diagnóstico. Neste contexto, a falta de vacina, de tratamento e o grande número de casos graves e morte, possibilitou a aprovação emergencial de diversos testes, que ainda necessitam de estudos populacionais para seu registro definitivo. Objetivo: Realizar uma revisão de literatura para avaliar as metodologias de diagnóstico disponíveis no Brasil, de acordo com a realidade local de saúde, explorando o momento epidemiológico a complexidade do teste e a finalidade da sua aplicação. Metodologia: Trata-se de um estudo bibliográfico, descritivo do tipo revisão de literatura. Foram utilizadas as seguintes bases de dados científicos para buscas: PUBMED, MEDLINE, LILACS E COCHRANE LIBRARY, através de descritores selecionados na plataforma DECS. Resultados: O cenário de diversos ensaios, baseados em diferentes metodologias, como os testes baseados em RNA viral, em detecção de antígenos virais ou de anticorpos, associados ao conhecimento da história natural do vírus, possibilita uma análise crítica do melhor diagnóstico de acordo com a clínica do paciente, os epidemiológicos, o objetivo do diagnóstico e a acurácia do ensaio. Atualmente, há mudança no padrão imunológico da população e a descrição de tipos e subtipos de SARS-CoV-2 com mudanças gênicas, que podem levar a mudanças na acurácia diagnóstica ou a re-emergência em surtos de doença grave. Conclusão: Ainda é incerto o caminho evolutivo da história natural da Covid-19 e os ensaios diagnósticos estão em diferentes estágios de desenvolvimento, validação e produção e cada tipo de teste tem suas próprias vantagens e desvantagens distintas inerentes a plataforma tecnológica de origem e uma combinação de tipos de testes usados em momentos diferentes pode ser útil para a condução clínica dos pacientes e no controle da pandemia por SARS-CoV-2.

Introduction: With the emergence of SARS-CoV-2, a large number of diagnostic tools were made available. In this context, the lack of vaccine, treatment and the large number of severe cases and death, allowed the emergency approval of several tests, which still require population studies for their definitive registration. Objective: To carry out a literature review to evaluate the diagnostic methodologies available in Brazil, according to the local health reality, exploring the epidemiological moment, the complexity of the test and the purpose of its application. Methodology: This is a bibliographic, descriptive study of the literature review type. The following scientific databases were used for searches: PUBMED, MEDLINE, LILACS AND COCHRANE LIBRARY, through selected descriptors on the DECS platform. Results: The scenario of several tests, based on different methodologies, such as tests based on viral RNA, on detection of viral antigens or antibodies, associated with knowledge of the natural history of the virus, allows a critical analysis of the best diagnosis according to the patient's clinical, epidemiological, diagnostic objective and assay accuracy. Currently, there is a change in the immune pattern of the population and the description of types and subtypes of SARS-CoV-2 with genetic changes, which can lead to changes in diagnostic accuracy or the re-emergence in outbreaks of severe disease. Conclusion: The evolutionary path of the natural history of Covid-19 is still uncertain and diagnostic assays are at different stages of development, validation and production and each type of test has its own distinct advantages and disadvantages inherent in the technology platform of origin and a combination of types of tests used at different times can be useful for the clinical management of patients and in the control of the SARS-CoV-2 pandemic.

Introducción: Con la aparición del SARS-CoV-2, se dispuso de un gran número de herramientas diagnósticas. En este contexto, la falta de vacuna, tratamiento y el gran número de casos graves y muerte, permitieron la aprobación de urgencia de varias pruebas, que aún requieren estudios poblacionales para su registro definitivo. Objetivo: Realizar una revisión bibliográfica para evaluar las metodologías diagnósticas disponibles en Brasil, de acuerdo con la realidad sanitaria local, explorando el momento epidemiológico, la complejidad de la prueba y la finalidad de su aplicación. Metodología: Se trata de un estudio bibliográfico, descriptivo, del tipo revisión de literatura. Para las búsquedas se utilizaron las siguientes bases de datos científicas PUBMED, MEDLINE, LILACS Y COCHRANE LIBRARY, a través de descriptores seleccionados en la plataforma DECS. Resultados: El escenario de varias pruebas, basadas en diferentes metodologías, como pruebas basadas en el ARN viral, en la detección de antígenos virales o anticuerpos, asociado al conocimiento de la historia natural del virus, permite un análisis crítico del mejor diagnóstico de acuerdo con la clínica del paciente, epidemiológica, objetivo diagnóstico y precisión de la prueba. Actualmente, hay un cambio en el patrón inmunológico de la población y la descripción de tipos y subtipos de SARS-CoV-2 con cambios genéticos, que pueden conducir a cambios en la precisión diagnóstica o la reaparición en brotes de enfermedad grave. Conclusiones: El camino evolutivo de la historia natural del Covid-19 es aún incierto y los ensayos de diagnóstico se encuentran en diferentes etapas de desarrollo, validación y producción y cada tipo de prueba tiene sus propias ventajas y desventajas distintas inherentes a la plataforma tecnológica de origen y una combinación de tipos de pruebas utilizadas en diferentes momentos puede ser útil para el manejo clínico de los pacientes y en el control de la pandemia de SARS- CoV-2.

Combination of RT-LAMP and fluorescence spectroscopy using chemometric techniques for an ultra-sensitive and rapid alternative for the detection of SARS-CoV-2.

The increased spread of COVID-19 caused by SARS-CoV-2 has made it necessary to develop more efficient, fast, accurate, specific, sensitive and easy-to-use detection platforms to overcome the disadvantages of gold standard methods (RT-qPCR). Here an approach was developed for the detection of the SARS-CoV-2 virus using the loop-mediated isothermal amplification (LAMP) technique for SARS-CoV-2 RNA target amplification in samples of nasopharyngeal swabs. The discrimination between positive and negative SARS-CoV-2 samples was achieved by using fluorescence spectra generated by the excitation of the LAMP's DNA intercalator dye at λ497 nm in a fluorescence spectrophotometer and chemometric tools. Exploratory analysis of the 83 sample spectra using principal component analysis (PCA) indicated a trend in differentiation between positive and negative samples resulting from the peak emission of the fluorescent dye. The classification was performed by partial least squares discriminant analysis (PLS-DA) achieving a sensitivity, a specificity and an accuracy of 100%, 95% and 89%, respectively for the discrimination between negative and positive samples from 1.58 to 0.25 ng L-1 after LAMP amplification. Therefore, this study indicates that the use of the LAMP technique in fluorescence spectroscopy may offer a fast (<1 hour), sensitive and low-cost method.

Aportes de la biotecnología en el diagnóstico de COVID-19 / Biotechnology contributions in COVID-19 diagnosis

Introducción: en diciembre del año 2019 surgió en China una neumonía viral; el virus fue identificado como un coronavirus SARS-CoV-2, que se propagó rápidamente de tal manera que se convirtió en pandemia. La alta contagiosidad y la presencia de portadores asintomáticos dificultaron el diagnóstico de la infección y la toma de decisiones sanitarias. Objetivo: el objetivo de esta revisión bibliográfica es presentar y describir las principales técnicas utilizadas actualmente para el diagnóstico de COVID-19 y establecer su relación con los conocimientos de distintas disciplinas y tecnologías emergentes que confluyen en la Biotecnología bioquímico-farmacéutica orientada a la Salud humana. Metodología: se realizó una revisión de la bibliografía disponible en PubMed a partir de enero de 2020 sobre las pruebas diagnósticas que se encuentran actualmente en uso, en el ámbito sanitario, para la detección y seguimiento de la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a métodos diagnósticos. Resultados: se presenta una importante cantidad de pruebas diagnósticas, basadas en diferentes tecnologías, que desempeñan un papel clave en la pandemia de COVID-19. Algunas de ellas muy sofisticadas, como la secuenciación genómica de próxima generación, otras más estándar, pero igualmente robustas, como la reacción en cadena de la polimerasa (PCR). También otras adaptadas para el brote pandémico, como la amplificación isotérmica de ácidos nucleicos mediada por bucle. Todas las mencionadas se consideran de tipo molecular, pero también existen las pruebas serológicas, como ELISA, que incluyen ensayos en plasma o de tipo inmunológico. Estas sirven para detectar anticuerpos frente a la exposición al virus o antígenos en personas potencialmente infectadas. Conclusiones: los procesos de investigación y desarrollo biotecnológicos aplicados al diagnóstico y los conocimientos científicos previos permitieron una respuesta tanto nacional como internacional rápida y eficaz en medio de una inédita pandemia global. En esta revisión destacamos las principales técnicas, en qué estadio se deben usar y qué información nos aportan. (AU)

Introduction: in December 2019, a viral pneumonia emerged in China, identifying the virus as a SARS-CoV-2 coronavirus, which spread rapidly in such a way that it became a pandemic. The high contagiousness and the presence of asymptomatic carriers make difficulted to diagnose the infection and to make health decisions. Target: the objective of this review is to present and describe the main techniques currently used for the diagnosis of COVID-19, and to establish their relationship with the knowledge of different disciplines and emerging technologies that converge in biochemical-pharmaceutical biotechnology oriented to human health. Methodology: a review of the literature available in Pubmed from January 2020 on the diagnostic tests that are currently in use in the health field, for the detection and monitoring of COVID-19 disease, was carried out. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to diagnostic methods. Results: a significant number of diagnostic tests are presented, based on different technologies, which play a key role in the COVID-19 pandemic. Some of them are very sophisticated, such as next-generation genomic sequencing, others more standard, but equally robust, such as polymerase chain reaction. Also others adapted for the pandemic outbreak such as loop-mediated isothermal amplification of nucleic acids. All of the aforementioned are considered molecular, but there are also serological tests, such as ELISA, which include plasma or immunological tests. These serve to detect antibodies against exposure to the virus or antigens in potentially infected people. Conclusions: biotechnological research and development processes applied to diagnosis and previous scientific knowledge allowed a rapid and effective national and international response in the midst of an unprecedented global pandemic. In this review we highlight the main techniques, at what stage they should be used and what information they provide us. (AU)

Nota Técnica N. 6/2022 - SES/GVEDT-03816 - Recomendações sobre a utilização do teste rápido para detecção de antígenos do Sars-CoV-2 / Technical Note N. 6/2022 - SES/GVEDT-03816 - Recommendations on the use of the rapid test to detect Sars-CoV-2 antigens

Esta nota tem o objetivo de orientar sobre a utilização do teste rápido para detecção de antígenos (TR-Ag) do SARS-CoV-2 e medidas de vigilância epidemiológica, visando intensificar a busca de casos suspeitos sintomáticos respiratórios e assintomáticos de infecção, identificar os casos confirmados, iniciar os cuidados em saúde precocemente, promover o isolamento, reduzir a disseminação, rastrear e testar os contatos

This note is intended to provide guidance on the use of the SARS-CoV-2 rapid antigen detection test (TR-Ag) and epidemiological surveillance measures, in order to intensify the search for suspected respiratory symptomatic and asymptomatic cases of infection, identify the confirmed cases, initiate health care early, promote isolation, reduce spread, trace and test contacts

Micro-Fourier-transform infrared reflectance spectroscopy as tool for probing IgG glycosylation in COVID-19 patients.

It has been reported that patients diagnosed with COVID-19 become critically ill primarily around the time of activation of the adaptive immune response. However the role of antibodies in the worsening of disease is not obvious. Higher titers of anti-spike immunoglobulin IgG1 associated with low fucosylation of the antibody Fc tail have been associated to excessive inflammatory response. In contrast it has been also reported that NP-, S-, RBD- specific IgA, IgG, and IgM are not associated with SARS-CoV-2 viral load, indicating that there is no obvious correlation between antibody response and viral antigen detection. In the present work the micro-Fourier-transform infrared reflectance spectroscopy (micro-FTIR) was employed to investigate blood serum samples of healthy and COVID-19-ill (mild or oligosymptomatic) individuals (82 healthcare workers volunteers in "Instituto de Infectologia Emilio Ribas", São Paulo, Brazil). The molecular-level-sensitive, multiplexing quantitative and qualitative FTIR data probed on 1 µL of dried biofluid was compared to signal-to-cutoff index of chemiluminescent immunoassays CLIA and ELISA (IgG antibodies against SARS-CoV-2). Our main result indicated that 1702-1785 [Formula: see text] spectral window (carbonyl C=O vibration) is a spectral marker of the degree of IgG glycosylation, allowing to probe distinctive sub-populations of COVID-19 patients, depending on their degree of severity. The specificity was 87.5 % while the detection rate of true positive was 100%. The computed area under the receiver operating curve was equivalent to CLIA, ELISA and other ATR-FTIR methods ([Formula: see text]). In summary, overall discrimination of healthy and COVID-19 individuals and severity prediction as well could be potentially implemented using micro-FTIR reflectance spectroscopy on blood serum samples. Considering the minimal and reagent-free sample preparation procedures combined to fast (few minutes) outcome of FTIR we can state that this technology is suitable for fast screening of immune response of individuals with COVID-19. It would be an important tool in prospective studies, helping investigate the physiology of the asymptomatic, oligosymptomatic, or severe individuals and measure the extension of infection dissemination in patients.

Cost-effectiveness of anti-SARS-CoV-2 antibody diagnostic tests in Brazil.

BACKGROUND: Although serologic tests for COVID-19 diagnosis are rarely indicated nowadays, they remain commercially available and widely used in Brazil. The objective of this study was to evaluate the cost-effectiveness of anti-SARS-CoV-2antibody diagnostic tests for COVID-19 in Brazil. METHODS: Eleven commercially available diagnostic tests, comprising five lateral-flow immunochromatographic assays (LFAs) and six immunoenzymatic assays (ELISA) were analyzed from the perspective of the Brazilian Unified Health System. RESULTS: The direct costs of LFAs ranged from US$ 11.42 to US$ 17.41and of ELISAs, from US$ 6.59 to US$ 10.31. Considering an estimated disease prevalence between 5% and 10%, the anti-SARS-CoV-2 ELISA (IgG) was the most cost-effective test, followed by the rapid One Step COVID-19 Test, at an incremental cost-effectiveness ratio of US$ 2.52 and US$ 1.26 per properly diagnosed case, respectively. Considering only the LFAs, at the same prevalence estimates, two tests, the COVID-19 IgG/IgM and the One Step COVID-19 Test, showed high effectiveness at similar costs. For situations where the estimated probability of disease is 50%, the LFAs are more costly and less effective alternatives. CONCLUSIONS: Nowadays there are few indications for the use of serologic tests in the diagnosis of COVID-19 and numerous commercially available tests, with marked differences are observed among them. In general, LFA tests are more cost-effective for estimated low-COVID-19-prevalences, while ELISAs are more cost-effective for high-pretest-probability scenarios.

Validación de pruebas rápidas de COVID-19. Isla de la Juventud, Cuba / COVID-19 rapid test validation. Isla de la Juventud, Cuba

Contar con métodos diagnósticos que reúnan ciertos atributos es vital para guiar las decisiones sanitarias, el contexto actual lo amerita. Con el objetivo de validar la capacidad de dos pruebas rápidas para detectar anticuerpos debido a la infección por SARS-CoV-2 en la Isla de la Juventud, Cuba, de abril a mayo de 2020, se realizó un estudio descriptivo de corte transversal de evaluación de pruebas rápidas: Wondfo (SARS-CoV-2 antibody test) y Lungene covid-19 IgG/IgM rapid test, en comparación con la prueba de reacción en cadena de la polimerasa en tiempo real. Se construyeron dos muestras homogéneas de 250 cada una, determinándose indicadores de validación. Se obtuvieron valores de sensibilidad de 6,6 por ciento y 8,3 por ciento respectivamente para cada prueba, mientras que la especificidad resultó superior para Wondfo (95 por ciento). Los valores predictivos positivos resultaron muy bajos, los negativos adecuados, superior en Lungene con el 94,8 por ciento. Los valores de razón de verosimilitud fueron clasificados como inútiles. En diferentes escenarios en cuanto a casos sintomáticos, se alcanzó sensibilidad del 50 por ciento en intervalo de 1 a 7 días para Wondfo. El área bajo la curva ROC para Wondfo fue 0,50 (IC95 por ciento=0,46-0,55) y para Lungene 0,46 (IC95 por ciento=0,38-0,55). El índice kappa para Wondfo fue de 0,025 y 0,010 para Lungene. Las pruebas rápidas exploradas mostraron muy baja sensibilidad, valor predictivo positivo y razón de verosimilitud inadecuada. La validez global de las pruebas no demostró un buen desempeño diagnóstico, marcado por el valor del área bajo la curva ROC(AU)

Having diagnostic methods that meet certain attributes is vital to guide health decisions, the current context warrants it. In order to validate the capacity of two rapid tests to detect antibodies due to SARS-CoV-2 infection in Isla de la Juventud, Cuba, from April to May 2020, a descriptive cross-sectional evaluation study was carried out. Rapid tests: Wondfo (SARS-CoV-2 antibody test) and Lungene covid-19 IgG/IgM, were compared to the real-time polymerase chain reaction test. Two homogeneous samples of 250 each were constructed, determining validation indicators. Sensitivity values of 6.6 percent and 8.3 percent respectively were obtained for each test, while the specificity was higher for Wondfo (95 percent). The positive predictive values were very low, the negative ones were adequate, higher in Lungene with 94.8 percent. Likelihood ratio values were classified as useless. In different scenarios in terms of symptomatic cases, sensitivity of 50 percent was reached in an interval of 1 to 7 days for Wondfo. The area under the ROC curve for Wondfo was 0.50 (95 percent CI = 0.46-0.55) and 0.46 for Lungene (95 percent CI = 0.38-0.55). The kappa index for Wondfo was 0.025 and 0.010 for Lungene. The rapid tests explored showed very low sensitivity, positive predictive value, and inadequate likelihood ratio. The global validity of the tests did not demonstrate a good diagnostic performance, marked by the value of the area under the ROC curve. The degree of agreement was poor(AU)