Towards classification and comprehensive analysis of AI-based COVID-19 diagnostic techniques: A survey.

The unpredictable pandemic came to light at the end of December 2019, known as the novel coronavirus, also termed COVID-19, identified by the World Health Organization (WHO). The virus first originated in Wuhan (China) and rapidly affected most of the world's population. This outbreak's impact is experienced worldwide because it causes high mortality risk, many cases, and economic falls. Around the globe, the total number of cases and deaths reported till November 12, 2022, were >600 million and 6.6 million, respectively. During the period of COVID-19, several diverse diagnostic techniques have been proposed. This work presents a systematic review of COVID-19 diagnostic techniques in response to such acts. Initially, these techniques are classified into different categories based on their working principle and detection modalities, i.e. chest X-ray imaging, cough sound or respiratory patterns, RT-PCR, antigen testing, and antibody testing. After that, a comparative analysis is performed to evaluate these techniques' efficacy which may help to determine an optimum solution for a particular scenario. The findings of the proposed work show that Artificial Intelligence plays a vital role in developing COVID-19 diagnostic techniques which support the healthcare system. The related work can be a footprint for all the researchers, available under a single umbrella. Additionally, all the techniques are long-lasting and can be used for future pandemics.

Improved heat shock method for extracting total RNA from nasopharyngeal swab samples even with low viral load.

This study aimed to improve the heat shock method as a cost-effective and time-efficient for total RNA extraction. We compared the effectiveness of two total RNA extraction methods by using Real-Time PCR for nasopharynx swabs. Include: I; use of a commercial total RNA extraction kit as a standard. II; utilized a modified heat shock method (MHS). Time, centrifuge speed and duration, proteinase K, and RNA carrier were optimized. The optimized parameters included treating the sample with 5 µg/µL at 56°C for 5 minutes, heating at 95°C for 5 minutes followed by thermal shock in ice for 3 minutes, adding 4 µg/µL RNA carrier at room temperature for 3 minutes, and centrifuging at 7000 rpm for 10 minutes. This optimization demonstrated a sensitivity and specificity of 100% (CI: 95%) even in samples with low viral load. Our in-house method presents a rapid, and cost-effective alternative for total RNA extraction.

Engineered two-dimensional nanomaterials based diagnostics integrated with internet of medical things (IoMT) for COVID-19.

More than four years have passed since an inimitable coronavirus disease (COVID-19) pandemic hit the globe in 2019 after an uncontrolled transmission of the severe acute respiratory syndrome (SARS-CoV-2) infection. The occurrence of this highly contagious respiratory infectious disease led to chaos and mortality all over the world. The peak paradigm shift of the researchers was inclined towards the accurate and rapid detection of diseases. Since 2019, there has been a boost in the diagnostics of COVID-19 via numerous conventional diagnostic tools like RT-PCR, ELISA, etc., and advanced biosensing kits like LFIA, etc. For the same reason, the use of nanotechnology and two-dimensional nanomaterials (2DNMs) has aided in the fabrication of efficient diagnostic tools to combat COVID-19. This article discusses the engineering techniques utilized for fabricating chemically active E2DNMs that are exceptionally thin and irregular. The techniques encompass the introduction of heteroatoms, intercalation of ions, and the design of strain and defects. E2DNMs possess unique characteristics, including a substantial surface area and controllable electrical, optical, and bioactive properties. These characteristics enable the development of sophisticated diagnostic platforms for real-time biosensors with exceptional sensitivity in detecting SARS-CoV-2. Integrating the Internet of Medical Things (IoMT) with these E2DNMs-based advanced diagnostics has led to the development of portable, real-time, scalable, more accurate, and cost-effective SARS-CoV-2 diagnostic platforms. These diagnostic platforms have the potential to revolutionize SARS-CoV-2 diagnosis by making it faster, easier, and more accessible to people worldwide, thus making them ideal for resource-limited settings. These advanced IoMT diagnostic platforms may help with combating SARS-CoV-2 as well as tracking and predicting the spread of future pandemics, ultimately saving lives and mitigating their impact on global health systems.

Performance evaluation of the cobas SARS-CoV-2 Duo, a novel qualitative and quantitative assay, for the detection of SARS-CoV-2 RNA.

IMPORTANCE: Quantitative SARS-CoV-2 tests for viral load are necessary to guide patient treatment, as well as to determine infection control measures and policies. Although the real-time RT-PCR assays can report the Ct value to estimate the viral load, there are several serious concerns regarding the use of Ct values. Importantly, Ct values can vary significantly among between- and within-run methods. The diagnostic performance of the cobas SARS-CoV-2 Duo is appropriate. It is a precise, accurate, and sensitive method for the detection of SARS-CoV-2 RNA and is comparable to two qualitative assays (the cobas SARS-CoV-2 and the Liat cobas SARS-CoV-2 and Inf A/B). In contrast, using the Ct value to estimate viral load is not reliable, and utilization of a quantitative detection test, such as the cobas SARS-CoV-2 Duo, to accurately measure the viral load is needed.

Assessment of thermal and temporal stability of SARS-CoV-2 samples using real-time qRT-PCR.

BACKGROUND: As per the guidelines of the Indian Council of Medical Research, nasopharyngeal and oropharyngeal swabs in viral transport medium (VTM) are to be stored at 4 °C for less than 5 days and for more than 5 days at -70 °C. Samples are not transported or stored as per prescribed conditions because of the limitations, resulting in an apprehensive diagnosis. The aim of the study was to test the stability of the SARS-CoV-2 sample stored in VTM at different temperatures. METHODS: In this study, the stability of 21 positive and 9 negative samples for SARS-CoV-2 was evaluated in commercial VTM at different temperatures (-80 °C, -20 °C, 4 °C, and 25 to 30 °C). Stability was checked for up to 50 days in the above storage conditions at different intervals. PathoDetect™ and Hi-PCR® kits were used for the detection of the four genes of SARS-CoV-2. The Cycle Threshold (Ct) value for determining the positivity of samples for PathoDetect™ was < 40 and for Hi-PCR® was < 38. RESULTS: The SARS-CoV-2 confirmatory genes (RdRp and E genes) and the internal housekeeping gene remained detectable even on the 50th day of the study. The Ct of the RdRp and E genes were found to increase with storage duration, but all positive samples remained positive till the end of the study, or the Ct value remained below the cut-off level. The negative samples gave consistent results until the end of the study. When the differences in Ct values were compared between the days in a set of experiments, they were not significantly different except in a few samples. CONCLUSION: The SARS-CoV-2 genetic materials in commercial VTM were stable at room temperature to -80 °C for 50 days.

Optimal allocation of scarce PCR tests during the COVID-19 pandemic.

BACKGROUND/AIM: During the coronavirus disease (COVID-19) pandemic, Germany and various other countries experienced a shortage of polymerase chain reaction (PCR) laboratory tests due to the highly transmissible SARS-CoV-2 Omicron variant that drove an unprecedented surge of infections. This study developed a mathematical model that optimizes diagnostic capacity with lab-based PCR testing. METHODS: A mathematical model was constructed to determine the value of PCR testing in relation to the pre-test probability of COVID-19. Furthermore, the model derives the lower and upper bounds for the threshold pre-test probability of the designated priority group. The model was applied in a German setting using the PCR test-positivity rate at the beginning of February 2022. RESULTS: The value function of PCR testing is bell-shaped with respect to the pre-test probability, reaching a maximum at a pre-test probability of 0.5. Based on a PCR test-positivity rate of 0.3 and assuming that at least two thirds of the tested population have a pre-test probability below, lower and higher pre-test probability thresholds are ≥ 0.1 and 0.7, respectively. Therefore, individuals who have a 25% likelihood of testing positive because they exhibit symptoms should be a higher priority for PCR testing. Furthermore, a positive rapid antigen test in asymptomatic individuals with no known exposure to COVID-19 should be confirmed using PCR. Yet, symptomatic individuals with a positive RAT should be excluded from PCR testing. CONCLUSION: A mathematical model that allows for the optimal allocation of scarce PCR tests during the COVID-19 pandemic was developed.

Increasing SARS-CoV-2 testing capacity through specimen pooling: An acute care center experience.

Innovation in laboratory testing algorithms to address seemingly uncontrollable global supply chain shortages in plastics and other consumables during emergencies such as the current COVID-19 pandemic have been urgently needed. We report our experience with specimen pooling on SARS-CoV-2 testing in an acute care hospital microbiology laboratory during a high testing demand period that exceeded available processing capacity. A fully automated four-in-one pooling algorithm was designed and validated. Correlation and agreement were calculated. A custom Microsoft Excel tool was designed for use by the technologists to aid interpretation, verification and result entry. Cost-per-test impact for pooling was measured in reference to the consumable cost and was denoted as the percentage reduction of cost versus the baseline cost-per-test of testing specimens individually. Validation showed a strong correlation between the signals observed when testing specimens individually versus those that were pooled. Average crossing point difference was 1.352 cycles (95% confidence interval of -0.235 and 2.940). Overall agreement observed between individually and pooled tested specimens was 96.8%. Stratified agreement showed an expected decreased performance of pooling for weakly positive specimens dropping below 60% after a crossing point of 35. Post-implementation data showed the consumable cost-savings achieved through this algorithm was 85.5% after 8 months, creating both testing and resource capacity. Pooling is an effective method to be used for SARS-CoV-2 testing during the current pandemic to address resource shortages and provide quick turnaround times for high test volumes without compromising performance.

Risk Estimation of Severe COVID-19 Based on Initial Biomarker Assessment Across Racial and Ethnic Groups.

CONTEXT.­: Disease courses in COVID-19 patients vary widely. Prediction of disease severity on initial diagnosis would aid appropriate therapy, but few studies include data from initial diagnosis. OBJECTIVE.­: To develop predictive models of COVID-19 severity based on demographic, clinical, and laboratory data collected at initial patient contact after diagnosis of COVID-19. DESIGN.­: We studied demographic data and clinical laboratory biomarkers at time of diagnosis, using backward logistic regression modeling to determine severe and mild outcomes. We used deidentified data from 14 147 patients who were diagnosed with COVID-19 by polymerase chain reaction SARS-CoV-2 testing at Montefiore Health System, from March 2020 to September 2021. We generated models predicting severe disease (death or more than 90 hospital days) versus mild disease (alive and fewer than 2 hospital days), starting with 58 variables, by backward stepwise logistic regression. RESULTS.­: Of the 14 147 patients, including Whites, Blacks, and Hispanics, 2546 (18%) patients had severe outcomes and 3395 (24%) had mild outcomes. The final number of patients per model varied from 445 to 755 because not all patients had all available variables. Four models (inclusive, receiver operating characteristic, specific, and sensitive) were identified as proficient in predicting patient outcomes. The parameters that remained in all models were age, albumin, diastolic blood pressure, ferritin, lactic dehydrogenase, socioeconomic status, procalcitonin, B-type natriuretic peptide, and platelet count. CONCLUSIONS.­: These findings suggest that the biomarkers found within the specific and sensitive models would be most useful to health care providers on their initial severity evaluation of COVID-19.

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)

Nonlinear interdependence of the results of measuring anti-SARS-CoV-2 IgG levels using Abbott and Euroimmun test systems.

BACKGROUND: There are significant number of tests used to determine the level of antibodies to SARS-CoV-2 which differ both in the methods underlying testing and in the antigenic targets used and classes of measured immunoglobulins. Comparison of the results obtained using various tests reveals their significant discrepancy when converted to the WHO recommended standard unit for measuring the level of specific immunoglobulins BAU/mL. The aim of this study is a comparison of anty-SARS-CoV-2 IgG levels, measured using test systems based on different methodological platforms - EuroImmun assay and Abbott assay. METHOD: Abbott uses the immunochemiluminescence method CLIA, EuroImmun uses the enzyme immunoassay method ELISA. The dependences of the measurement error on the level of antibodies for the two test systems were approximated by power functions using the least squares method. The nonlinear relation of antibody levels values measured by Abbott assay and Euroimmun assay was approximated by an asymptotic function. RESULTS: The study involved 112 people. Our results confirm the fallacy of using a single conversion coefficient in BAU/mL for anti-SARS-CoV-2 IgG levels measured by Abbott and EuroImmun. To describe the interdependence of anti-SARS-CoV-2 IgG Abbott and EuroImmun levels, we offer the function y = 18/π arctan(0.0009x) and a calculator that allows to easily recalculate the results obtained using these tests. CONCLUSION: The non-linear nature of the interdependence of the measured anti-SARS-CoV-2 antibodies levels on the levels magnitude is one of the main reasons for the discrepancy between the tests results when converted to BAU/mL using a single conversion coefficient.

Should rapid antigen tests be first-line for COVID-19 testing? Results of a prospective urban cohort study.

BACKGROUND: A highly accurate, rapid, and low-cost COVID-19 test is essential for guiding isolation measures. To date, the most widely used tests are either nucleic acid amplification tests or antigen tests. The objective of this study is to further assess the diagnostic performance of the Binax-CoV2 rapid antigen test in comparison to the current gold standard reverse transcription quantitative polymerase chain reaction (RT-qPCR), with additional analysis of symptomatology and cycle threshold utility. METHODS: This is a prospective cohort study performed between November and December 2020. Individuals who presented to COVID-19 testing events and received both RT-qPCR and a rapid antigent test were included. Testing occurred at the emergency department of an urban hospital and at a community mobile unit. No fees or appointments were required. Individuals self-reported the presence or absence of symptoms and history of positive COVID-19 test within the previous two weeks. Trained staff collected two subsequent nasopharyngeal swabs of both nares. One set of swabs underwent RT-qPCR and the other underwent Binax-CoV2 assay per manufacturer guidelines. RESULTS: A total of 390 patients were included, of which 302 were from the community site. Of these 302, 42 (14%) were RT-qPCR positive. Of the 42 RT-qPCR positive, 30 (71.4%) were also positive by Binax-CoV2. The Binax-CoV2 test had a sensitivity of 71.4% (95% CI: 55%-84%) and a specificity of 99.6% (95% CI: 98%-100%) in this population. Performance of the Binax-CoV2 test performed better in individuals with higher viral load. For symptomatic patients with cycle threshold < 20, sensitivity reached 100%. CONCLUSIONS: The Binax-CoV2 assay's specificity and sensitivity in individuals with high viral load makes it a suitable first-line test for detecting COVID-19. However, given the assay's measured sensitivity, a negative result on the Binax-CoV2 assay may warrant additional testing with more sensitive tests, such as the RT-qPCR. This is particularly the case with high clinical suspicion for an active SARS-CoV-2 infection even after a negative Binax-CoV2 result.

Swab the Throat as Well as the Nose? The Debate Over the Best Way to Test for SARS-CoV-2.

This Medical News article discusses whether swabbing both the nose and the throat might improve the sensitivity of rapid antigen COVID-19 tests.

Evaluation of diagnostic performance of a rapid antigen test in diagnosing COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is our time's major global health crisis and the greatest health challenge. Reverse transcription-polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the gold standard technique for diagnosis of symptomatic cases and asymptomatic carriers. By 2020, antigen rapid tests have been approved for use in Covid-19 testing by regulatory bodies all over the world owing to their benefits as they are rapid and cost effective. This work aimed to determine the diagnostic sensitivity and accuracy of the SARS-CoV-2 rapid antigen test in the detection of SARS-CoV-2 infection compared to RT-PCR data. The study included 111 symptomatic COVID-19 patients and 20 control subjects. Of the 111 study patients, 91 patients (81.98%) were positive by RT-PCR and 20 patients negative. The BIOZEK antigen COVID-19 Ag rapid test device was evaluated using sera from the 111 symptomatic COVID-19 patients. Of the 91 RT-PCR positive patients, 81 (90.1%) were positive by the antigen rapid diagnostic test (Ag-RDT). The control subjects were negative by both tests. The overall sensitivity, specificity, PPV, NPV, and accuracy of the Ag-RDT were 91.11%, 100%, 100%, 68.9%, and 91.8%, respectively and these increased as the level of viremia increased. In conclusion, the used Ag-RDT showed high sensitivity and accuracy for detecting of a SARS-CoV-2 infection, especially when the viral load was high. However, the test lacks sensitivity particularly in those with low viral load.

Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform.

OBJECTIVES: To describe a high-sensitivity SARS-CoV-2 antigen test that is based on the fully automated light-initiated chemiluminescent immunoassay (LiCA®), and to validate its analytical characteristics and clinical agreement on detecting SARS-CoV-2 infection against the reference molecular test. METHODS: Analytical performance was validated and detection limits were determined using different types of nucleocapsid protein samples. 798-pair anterior nasal swab specimens were collected from hospitalized patients and asymptomatic screening individuals. Agreement between LiCA® antigen and real-time reverse transcription polymerase chain reaction (rRT-PCR) was evaluated. RESULTS: Repeatability and within-lab precision were 1.6-2.3%. The C5∼C95 interval was -5.1-4.6% away from C50. Detection limits in average (SD) were 325 (±141) U/mL on the national reference panel, 0.07 (±0.04) TCID50/mL on active viral cultures, 0.27 (±0.09) pg/mL on recombinant nucleocapsid proteins and 1.07 (±1.01) TCID50/mL on inactivated viral suspensions, respectively. LiCA detected a median of 374-fold (IQR 137-643) lower levels of the viral antigen than comparative rapid tests. As reference to the rRT-PCR method, overall sensitivity and specificity were determined to be 97.5% (91.4-99.7%) and 99.9% (99.2-100%), respectively. Total agreement between both methods was 99.6% (98.7-99.9%) with Cohen's kappa 0.98 (0.96-1). A positive detection rate of 100% (95.4-100%) was obtained as Ct≤37.8. CONCLUSIONS: The LiCA® system provides an exceptionally high-sensitivity and fully automated platform for the detection of the SARS-CoV-2 antigen in nasal swabs. The assay may have high potential use for large-scale population screening and surveillance of COVID-19 as an alternative to the rRT-PCR test.

An Unusual Retained Choanal Foreign Body: A Possible Complication of COVID-19 Testing With Nasopharyngeal Swab.

Testing for coronavirus disease 2019 is critical in controlling the pandemic all over the world. Diagnosis of severe acute respiratory syndrome coronavirus-2 infection is based on real-time polymerase chain reaction performed on nasopharyngeal swab. If not adequately performed, the viral specimen collection can be painful and lead to complications. We present a complication occurred during a nasopharyngeal swab collection performed in a noncooperative patient where the plastic shaft of the swab fractured during the procedure, resulting in swab tip retention deep into the nasal cavity. The foreign body was found endoscopically, stuck between the nasal septum and the superior turbinate tail at the upper level of the left choana and removed under general anesthesia in a negative pressure operating room with the health care personnel wearing personal protective equipment. Unpleasant complications like the one described can happen when the swab is collected without the necessary knowledge of nasal anatomy or conducted inappropriately, especially in noncooperative patients. Moreover, the design of currently used viral swabs may expose to accidental rupture, with risk of foreign body retention in the nasal cavities. In such cases, diagnosis and treatment are endoscopy-guided procedures performed in an adequate setting to minimize the risk of spreading of the pandemic.