Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting

Abstract Background Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation. Methods Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT). Results Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%–60.4%) to 67.9% (95% CI, 59.4%–75.6%), and specificities from 95.6% (95% CI, 89.2%–98.8%) to 100.0% (95% CI, 96.1%–100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%–75.6%), increasing to 93.8% (95% CI, 85.0%–98.3%) for samples >14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%–68.4%), rising to 91.2% (95% CI, 81.8%–96.7%) for samples >14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%–97.5%). Conclusions Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.

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Evaluation of serological tests for SARS-CoV-2: Implications for serology testing in a low-prevalence setting

10.1101/2020.05.31.20118273 ◽

2020 ◽

Cited By ~ 1

Author(s):

Katherine Bond ◽

Suellen Nicholson ◽

Seok Ming Lim ◽

Theo Karapanagiotidis ◽

Eloise Williams ◽

...

Keyword(s):

Symptom Onset ◽

Optimal Algorithm ◽

Point Of Care ◽

Performance Characteristics ◽

Serological Tests ◽

Specimen Collection ◽

Commercial Enzyme Immunoassay ◽

Low Prevalence ◽

Flow Devices

AbstractBackgroundRobust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little pre-market validation.MethodsPerformance characteristics for five PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralisation test (sVNT).ResultsSensitivities for PoCT ranged from 51.8% (95% CI 43.1 to 60.4%) to 67.9% (95% CI 59.4–75.6%), and specificities from 95.6% (95% CI 89.2–98.8%) to 100.0% (95% CI 96.1–100.0%). Overall ELISA sensitivity for either IgA or IgG detection was 67.9% (95% CI 59.4–75.6), increasing to 93.8% (95% CI 85.0–98.3%) for samples > 14 days post symptom onset. Overall, sVNT sensitivity was 60.9% (95% CI 53.2–68.4%), rising to 91.2%% (95% CI 81.8–96.7%) for samples collected > 14 days post-symptom onset, with a specificity 94.4% (95% CI 89.2–97.5%),ConclusionPerformance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in the reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.

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Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

BMJ ◽

10.1136/bmj.m2516 ◽

2020 ◽

pp. m2516 ◽

Cited By ~ 111

Author(s):

Mayara Lisboa Bastos ◽

Gamuchirai Tavaziva ◽

Syed Kunal Abidi ◽

Jonathon R Campbell ◽

Louis-Patrick Haraoui ◽

...

Keyword(s):

Systematic Review ◽

Diagnostic Accuracy ◽

Sensitivity And Specificity ◽

Symptom Onset ◽

Serological Test ◽

Point Of Care ◽

Meta Analysis ◽

Risk Of Bias ◽

Serological Tests ◽

Immunoglobulin Class

AbstractObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).DesignSystematic review and meta-analysis.Data sourcesMedline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.Eligibility criteria and data analysisEligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.Main outcome measuresThe primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.Results5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).ConclusionHigher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.Study registrationPROSPERO CRD42020179452.

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Evaluation of Six Commercial Mid- to High-Volume Antibody and Six Point-of-Care Lateral Flow Assays for Detection of SARS-CoV-2 Antibodies

Journal of Clinical Microbiology ◽

10.1128/jcm.01361-20 ◽

2020 ◽

Vol 58 (10) ◽

Cited By ~ 12

Author(s):

Carmen L. Charlton ◽

Jamil N. Kanji ◽

Kam Johal ◽

Ashley Bailey ◽

Sabrina S. Plitt ◽

...

Keyword(s):

Symptom Onset ◽

Point Of Care ◽

Acute Infection ◽

High Volume ◽

Respiratory Viruses ◽

Cross Reactivity ◽

Lateral Flow ◽

Serological Tests ◽

Deep Blue ◽

Lateral Flow Assays

ABSTRACT Coronavirus disease (COVID) serological tests are essential to determine the overall seroprevalence of a population and to facilitate exposure estimates within that population. We performed a head-to-head assessment of enzyme immunoassays (EIAs) and point-of-care lateral flow assays (POCTs) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Demographics, symptoms, comorbidities, treatment, and mortality of patients whose sera were used were also reviewed. Six EIAs (Abbott, Affinity, Bio-Rad, DiaSorin, Euroimmun, and Roche) and six POCTs (BTNX, Biolidics, Deep Blue, Genrui, Getein BioTech, and Innovita) were evaluated for the detection of SARS-CoV-2 antibodies in known COVID-19-infected individuals. Sensitivity of EIAs ranged from 50 to 100%, with only four assays having overall sensitivities of >95% after 21 days after symptom onset. Notably, cross-reactivity with other respiratory viruses (parainfluenza virus [PIV-4] [n = 5], human metapneumovirus [hMPV] [n = 3], rhinovirus/enterovirus [n = 1], CoV-229E [n = 2], CoV-NL63 [n = 2], and CoV-OC43 [n = 2]) was observed; however, overall specificity of EIAs was good (92 to 100%; all but one assay had specificity above 95%). POCTs were 0 to 100% sensitive >21 days after onset, with specificity ranging from 96 to 100%. However, many POCTs had faint banding and were often difficult to interpret. Serology assays can detect SARS-CoV-2 antibodies as early as 10 days after symptom onset. Serology assays vary in their sensitivity based on the marker (IgA/IgM versus IgG versus total) and by manufacturer; however, overall only 4 EIAs and 4 POCTs had sensitivities of >95% >21 days after symptom onset. Cross-reactivity with other seasonal coronaviruses is of concern. Serology assays should not be used for the diagnosis of acute infection but rather in carefully designed serosurveys to facilitate understanding of seroprevalence in a population and to identify previous exposure to SARS-CoV-2.

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Point of Care Neurosonogram in Neonates - Utility and Prognostic Value

American Journal of Sonography ◽

10.25259/ajs-41-2018 ◽

2019 ◽

Vol 2 ◽

pp. 1

Author(s):

Bhushita Lakhkar ◽

M. M. Patil ◽

Bhavana Lakhkar ◽

Bhushan Lakhkar

Keyword(s):

Neonatal Intensive Care ◽

Point Of Care ◽

Color Doppler ◽

Periventricular Leukomalacia ◽

Birth Asphyxia ◽

Common Finding ◽

Term Outcome ◽

Long Term Outcome ◽

Doppler Study

Objective The study aimed to utilize the neurosonographic findings in neonates in early diagnosis, prediction of their long-term outcome, parental counseling, and early intervention. Methods The study was carried out in neonatal intensive care unit (NICU) of Shri BM Patil Medical College and Hospital. All preterms and term babies with neurological clinical findings were included in the study. Neurosonogram was done within first 7 days in preterms and when indicated in terms. Philips HD11XE ultrasound and color Doppler unit were used with a small footprint probe. Color Doppler images for vessels were performed for screening of vascular changes. Results A total of 215 babies were included, of which 80 (32%) were term and the rest were preterm. Mean weight of term babies was 2.8 kg and that of preterm was 1.2 kg.Among term babies, 78% showed ultrasound abnormality, and among preterm, 42%showed abnormalities. Among term babies, 60% and, among preterms, 30% had birth asphyxia. Periventricular leukomalacia was the most common and earliest finding followed by thalamic hyperechogenicity and intracranial hemorrhage. Intraventricular hemorrhage was more common in preterm babies. Other common finding in NICU was meningitis which was more common in pretrms. Among congenital anomalies, corpus callosal agenesis was more common. Conclusions Point of care ultrasonography along with Doppler study is very useful and safe to use in NICUs. It helps in diagnosis, patient management as well as prediction of many short- and long-term outcomes.

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A long-term survey on Mycobacterium tuberculosis complex in wild mammals from a bovine tuberculosis low prevalence area

European Journal of Wildlife Research ◽

10.1007/s10344-021-01489-z ◽

2021 ◽

Vol 67 (3) ◽

Author(s):

Lucía Varela-Castro ◽

Xeider Gerrikagoitia ◽

Vega Alvarez ◽

María V. Geijo ◽

Marta Barral ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Bovine Tuberculosis ◽

Mycobacterium Tuberculosis Complex ◽

Tuberculosis Complex ◽

Wild Mammals ◽

Low Prevalence ◽

Long Term Survey

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Converging Robotic Technologies in Targeted Neural Rehabilitation: A Review of Emerging Solutions and Challenges

Sensors ◽

10.3390/s21062084 ◽

2021 ◽

Vol 21 (6) ◽

pp. 2084

Author(s):

Kostas Nizamis ◽

Alkinoos Athanasiou ◽

Sofia Almpani ◽

Christos Dimitrousis ◽

Alexander Astaras

Keyword(s):

Point Of Care ◽

Brain Activity ◽

Technological Evolution ◽

Future Directions ◽

Specific Patient ◽

Cord Injury ◽

Hybrid Solutions ◽

New Research ◽

Rehabilitation Robotic

Recent advances in the field of neural rehabilitation, facilitated through technological innovation and improved neurophysiological knowledge of impaired motor control, have opened up new research directions. Such advances increase the relevance of existing interventions, as well as allow novel methodologies and technological synergies. New approaches attempt to partially overcome long-term disability caused by spinal cord injury, using either invasive bridging technologies or noninvasive human–machine interfaces. Muscular dystrophies benefit from electromyography and novel sensors that shed light on underlying neuromotor mechanisms in people with Duchenne. Novel wearable robotics devices are being tailored to specific patient populations, such as traumatic brain injury, stroke, and amputated individuals. In addition, developments in robot-assisted rehabilitation may enhance motor learning and generate movement repetitions by decoding the brain activity of patients during therapy. This is further facilitated by artificial intelligence algorithms coupled with faster electronics. The practical impact of integrating such technologies with neural rehabilitation treatment can be substantial. They can potentially empower nontechnically trained individuals—namely, family members and professional carers—to alter the programming of neural rehabilitation robotic setups, to actively get involved and intervene promptly at the point of care. This narrative review considers existing and emerging neural rehabilitation technologies through the perspective of replacing or restoring functions, enhancing, or improving natural neural output, as well as promoting or recruiting dormant neuroplasticity. Upon conclusion, we discuss the future directions for neural rehabilitation research, diagnosis, and treatment based on the discussed technologies and their major roadblocks. This future may eventually become possible through technological evolution and convergence of mutually beneficial technologies to create hybrid solutions.

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COVID-19 Seroprevalence among Healthcare Workers of a Large COVID-19 Hospital in Rome Reveals Strengths and Limits of Two Different Serological Tests

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052650 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2650

Author(s):

Giuseppe Vetrugno ◽

Daniele Ignazio La Milia ◽

Floriana D’Ambrosio ◽

Marcello Di Pumpo ◽

Roberta Pastorino ◽

...

Keyword(s):

Blood Test ◽

Healthcare Workers ◽

Point Of Care ◽

Venous Blood ◽

Administrative Staff ◽

Serological Tests ◽

Predictive Values ◽

Work From Home ◽

Significant Difference ◽

Sensitivity Specificity

Healthcare workers are at the forefront against COVID-19, worldwide. Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS was enlisted as a COVID-19 hospital, the healthcare workers deployed to COVID-19 wards were separated from those with limited/no exposure, whereas the administrative staff were designated to work from home. Between 4 June and 3 July 2020, an investigation was conducted to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies among the employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity, and predictive values were determined with reverse-transcription polymerase chain reaction on nasal/oropharyngeal swabs as the diagnostic gold standard. The participants enrolled amounted to 4777. Seroprevalence was 3.66% using the POC test and 1.19% using the venous blood test, with a significant difference (p < 0.05). The POC test sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among the low-risk populations, the POC test’s predictive values were 58.33% (positive) and 98.23% (negative), whereas those of the venous blood test were 92.86% (positive) and 98.53% (negative). According to our study, these serological tests cannot be a valid alternative to diagnose COVID-19 infection in progress.

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