Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.
TL;DR: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed, as available evidence does not support the continued use of existing point-of-care serological Tests for coronavirus disease-2019.
Abstract: Objective To determine the diagnostic accuracy of
serological tests for coronavirus disease-2019
(covid-19). Design Systematic review and meta-analysis. Data sources Medline, 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
analysis Eligible 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 measures The 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. Results 5016 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%). Conclusion Higher 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 registration PROSPERO CRD42020179452.
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TL;DR: The results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza.
Abstract: Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
571 citations
Cites background from "Diagnostic accuracy of serological ..."
...Indeed, a recent systematic review and meta-analysis found very substantial divergences in sensitivity and specificity of COVID-19 serological tests.[8]...
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TL;DR: In this paper, a prospective study of the first 100 consecutive patients (50 SARS-CoV-2 laboratory-positive and 50 laboratory-negative) presenting to our Neuro-Covid-19 clinic between May and November 2020 was conducted.
Abstract: OBJECTIVE: Most SARS-CoV-2-infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non-hospitalized Covid-19 "long haulers". METHODS: This is a prospective study of the first 100 consecutive patients (50 SARS-CoV-2 laboratory-positive (SARS-CoV-2+ ) and 50 laboratory-negative (SARS-CoV-2- ) individuals) presenting to our Neuro-Covid-19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid-19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient-reported quality of life measures and standardized cognitive assessments. RESULTS: Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: "brain fog" (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS-CoV-2+ than SARS-CoV-2- patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS-CoV-2+ patients performed worse in attention and working memory cognitive tasks compared to a demographic-matched US population (T-score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01). INTERPRETATION: Non-hospitalized Covid-19 "long haulers" experience prominent and persistent "brain fog" and fatigue that affect their cognition and quality of life.
345 citations
TL;DR: Based on a systematic review and meta-analysis of published evidence on COVID-19 until July, 2020, the IFR of the disease across populations is 0.68% (0.53-0.82%).
336 citations
02 Dec 2020
TL;DR: A multiplexed, portable, wireless electrochemical platform for ultra-rapid detection of COVID-19: the SARS-CoV-2 RapidPlex, which detects viral antigen nucleocapsid protein, IgM and IgG antibodies, as well as the inflammatory biomarker C-reactive protein, based on the mass-producible laser-engraved graphene electrodes.
Abstract: The COVID-19 pandemic is an ongoing global challenge for public health systems. Ultrasensitive and early identification of infection is critical in preventing widespread COVID-19 infection by presymptomatic and asymptomatic individuals, especially in the community and in-home settings. We demonstrate a multiplexed, portable, wireless electrochemical platform for ultra-rapid detection of COVID-19: the SARS-CoV-2 RapidPlex. It detects viral antigen nucleocapsid protein, IgM and IgG antibodies, as well as the inflammatory biomarker C-reactive protein, based on our mass-producible laser-engraved graphene electrodes. We demonstrate ultrasensitive, highly selective, and rapid electrochemical detection in the physiologically relevant ranges. We successfully evaluated the applicability of our SARS-CoV-2 RapidPlex platform with COVID-19-positive and COVID-19-negative blood and saliva samples. Based on this pilot study, our multiplexed immunosensor platform may allow for high-frequency at-home testing for COVID-19 telemedicine diagnosis and monitoring.
302 citations
Additional excerpts
...Serologic assays detect circulating antibodies specific to SARS-CoV-2 antigens, including the nucleocapsid protein and the outer spike protein.(9,18) However, it is not possible to differentiate between asymptomatic carriers and immune persons using antibody detection....
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TL;DR: A meta-analysis to estimate the global and regional SARS-CoV-2 seroprevalence rates in humans, and to assess whether serop revalence associates with geographical, climatic and socio-demographic factors, suggested an association with income, human development and climate change.
267 citations
Cites result from "Diagnostic accuracy of serological ..."
...Two recent meta-analyses [50, 51] showed that sensitivities were consistently lower for the LFIA (66-80%) assay compared with ELISA (84Jo urn al Pr e-p roo f...
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TL;DR: Copyright (©) 1999–2012 R Foundation for Statistical Computing; permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and permission notice are preserved on all copies.
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.
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TL;DR: In this article, a model is described in an lmer call by a formula, in this case including both fixed-and random-effects terms, and the formula and data together determine a numerical representation of the model from which the profiled deviance or the profeatured REML criterion can be evaluated as a function of some of model parameters.
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"Diagnostic accuracy of serological ..." refers background in this paper
...†Cassaniti et al15 includes two distinct populations, patients who were triaged or admitted to hospital, with different study design (cohort and case-control)....
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TL;DR: An Explanation and Elaboration of the PRISMA Statement is presented and updated guidelines for the reporting of systematic reviews and meta-analyses are presented.
Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.
Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.
The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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TL;DR: The meaning and rationale for each checklist item is explained, and an example of good reporting is included and, where possible, references to relevant empirical studies and methodological literature are included.
Abstract: Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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TL;DR: The QUADAS-2 tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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8,370 citations