When to test for COVID-19 using RT-PCR: a systematic review.
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ABSTRACT: Objectives
The aim of this study was to evaluate the time in days between symptom onset and first positive RT-PCR result for COVID-19.Methods
This systematic review was conducted in the MEDLINE (PubMed), Embase, and Scopus databases using the following descriptors: "COVID-19", "SARS-CoV-2", "coronavirus", "RT-PCR", "real time PCR" and "diagnosis".Results
The included studies were conducted in 31 different countries and reported on a total of 6831 patients. The median age of the participants was 49.95 years. The three most common symptoms were fever, cough, and dyspnea, which affected 4012 (58.68%), 3192 (46.69%), and 2009 patients (29.38%), respectively. Among the 90 included studies, 13 were prospective cohorts, 15 were retrospective cohorts, 36 were case reports, 20 were case series, and 6 were cross-sectional studies. The overall mean time between symptom onset and positive test results was 6.72 days. Fourteen articles were analyzed separately for the temporal profile of RT-PCR tests, and the best performance was on days 22-24, when 98% of tests resulted positive.Conclusions
These findings corroborate the RT-PCR COVID-19 testing practices of some health units. In addition, the most frequently described symptoms of these patients can be considered the initial symptoms of infection and used in decision-making about RT-PCR testing.
SUBMITTER: Dos Santos PG
PROVIDER: S-EPMC9233872 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.MethodsWe searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.ResultsWe included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues.ConclusionsThere is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence).Systematic review registrationProtocol available on the OSF website: https://tinyurl.com/vvbgqya.
| S-EPMC7728293 | biostudies-literature
Project description:The purpose of this systematic review is to evaluate the test accuracy of reverse-transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription-PCR (RT-PCR) for the diagnosis of coronavirus disease 2019 (COVID-19). We comprehensively searched PUBMED, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until September 1, 2021. We included clinical studies assessing the sensitivity and specificity of RT-PCR and RT-LAMP using respiratory samples. Thirty-three studies were included with 9360 suspected cases of SARS-CoV-2 infection. The RT-PCR or other comprehensive diagnostic method was defined as the reference method. The results showed that the overall pooled sensitivity of RT-PCR and RT-LAMP was 0.96 (95 % CI, 0.93-0.98) and 0.92 (95 % CI, 0.85-0.96), respectively. RT-PCR and RT-LAMP had a 0.06 (95 % CI, 0.04-0.08) and 0.12 (95 % CI, 0.06-0.16) false-negative rates (FNR), respectively. Moreover, subgroup analysis showed mixed sampling and multiple target gene diagnosis methods had better diagnostic value than single-site sampling and a single target gene. The sensitivity and FNR were also significantly affected by the reference method. Comparing RT-LAMP with established suboptimal RT-PCR may exaggerate the performance of RT-LAMP. RT-PCR and RT-LAMP showed high values in the diagnosis of COVID-19, but there was still a FNR of about 6%-12%.
| S-EPMC8629515 | biostudies-literature
Project description:BackgroundWith the increased number of patients discharged after having COVID-19, more and more studies have reported cases whose retesting was positive (RP) during the convalescent period, which brings a new public health challenge to the world.MethodsWe searched PubMed, Web of Science, The Cochrane Library, CNKI, WanFang and VIP from December 1, 2019 to December 31, 2020. The included studies were assessed using JBI critical appraisal tools and Newcastle-Ottawa Scale. The RP rate of discharge patients was analyzed by a meta-analysis. We adhered to PRISMA reporting guideline.FindingsWe have included 117 studies with 2669 RP participants after discharge. The methodological quality of 66 case reports were low to high, 42 case series and 3 cohort study were moderate to high, 3 case-control studies were moderate and 3 cross-sectional studies were low to moderate. The clinical manifestations of most RP patients were mild or asymptomatic, and CT imaging and laboratory examinations were usually normal. The existing risk factors suggest that more attention should be paid to sever patients, elderly patients, and patients with co-morbidities. The summary RP rate was 12·2% (95% CI 10·6-13·7) with high heterogeneity (I2 = 85%).InterpretationTo date, the causes and risk factors of RP result in discharged patients are not fully understood. High-quality etiological and clinical studies are needed to investigate these issues to further help us to make strategies to control and prevent its occurrence.
| S-EPMC8052132 | biostudies-literature
Project description:ObjectivesTo compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) as the reference standard in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients.DesignA systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A search of electronic information was conducted using the following databases: MEDLINE, EMBASE, EMCARE, CINAHL and the Cochrane Central Register of Controlled Trials.SettingStudies that compared the diagnostic performance within the same patient cohort of chest CT scan versus RT-PCR in COVID-19 suspected patients.ParticipantsThirteen non-randomised studies enrolling 4092 patients were identified.Main outcome measuresSensitivity, specificity and accuracy were primary outcome measures. Secondary outcomes included other test performance characteristics and discrepant findings between both investigations.ResultsChest CT had a median sensitivity, specificity and accuracy of 0.91 (range 0.82-0.98), 0.775 (0.25-1.00) and 0.87 (0.68-0.99), respectively, with RT-PCR as the reference. Importantly, early small, China-based studies tended to favour chest CT versus later larger, non-China studies.ConclusionsA relatively high false positive rate can be expected with chest CT. It is possible it may still be useful to provide circumstantial evidence, however, in some patients with a suspicious clinical presentation of COVID-19 and negative initial Severe Acute Respiratory Syndrome Coronavirus 2 RT-PCR tests, but more evidence is required in this context. In acute cardiorespiratory presentations, negative CT scan and RT-PCR tests is likely to be reassuring.
| S-EPMC8127597 | biostudies-literature
Project description:BackgroundManagement of large numbers of reverse transcriptase-polymerase chain reactions (RT-PCR) for diagnosis of coronavirus 2019 disease (COVID-19) requires robust infrastructures, located in dedicated premises with a high standard of biosafety procedures, and well-trained personnel. The handling of a "run-of-river sample" to obtain rapid reporting of results is challenging.MethodsWe studied the clinical performance of the Idylla™ SARS-CoV-2 Test (index test) on a platform capable of fully automated nucleic acid testing including extraction, amplification, and detection in a single-use cartridge to establish the diagnosis of COVID-19. The study was conducted on a prospective cohort of 112 volunteers with recent symptoms and an unknown SARS-CoV-2 status who came to free screening centers of the Nice metropolitan area. All subjects underwent bilateral nasopharyngeal sampling. One sample was processed using the index test, the other using the standard of care RT-PCR. Samples were treated blind.ResultsMost of the participants (70%) were sampled within 4 days of symptom onset. Forty-five (40.2%) were positive for COVID-19. No clinical symptoms were distinguished between SARS-CoV-2 RT-PCR positive and negative subjects except anosmia and dysgeusia. Positive and negative agreement between the index and the standard of care test was 100%.ConclusionsThe Idylla™ SARS-CoV-2 Test is very sensitive, specific, rapid and easy to use in a near-patient RT-PCR approach to distinguish between symptomatic SARS-CoV-2 positive and negative patients in selected settings.
| S-EPMC8263856 | biostudies-literature
Project description:ObjectiveDuring the follow-up of patients recovered from coronavirus disease 2019 (COVID-19) in the quarantine and observation period, some of the cured patients showed positive results again. The recurrent positive RT-PCR test results drew widespread concern. We observed a certain number of cured COVID-19 patients with positive RT-PCR test results and try to analyze the factors that caused the phenomenon.MethodsWe conducted an observational study in COVID-19 patients discharged from 6 rehabilitation stations in Wuhan, China. All observed subjects met the criteria for hospital discharge and were in quarantine. Data regarding age, sex, body mass index (BMI), course of disease, comorbidity, smoking status and alcohol consumption, symptoms in and out of quarantine, and intervention were collected from the subjects' medical records and descriptively analyzed. The main outcome of this study was the RT-PCR test result of the observed subjects at the end of quarantine (negative or positive). Logistic regression analysis was used to identify the influencing factors related to recurrent positive RT-PCR test results.ResultsIn this observational study, 420 observed subjects recovered from COVID-19 were included. The median age was 56 years, 63.6% of the subjects were above 50 years old, and 50.7% (213/420) were female. The most common comorbidities were hypertension [26.4% (111/420)], hyperlipidemia [10.7% (45/420)], and diabetes [10.5% (44/420)]. 54.8% (230/420) manifested one or more symptoms at the beginning of the observation period, the most common symptoms were cough [27.6% (116/420)], shortness of breath 23.8% (100/420)], and fatigue [16.2% (68/420)], with fever rare [2.6% (11/420)]. A total of 325 subjects were exposed to comprehensive intervention; 95 subjects were absence of intervention. The recurrence rate of positive RT-PCR test results with comprehensive intervention was 2.8% (9/325), and that with no intervention was 15.8% (15/95). The results of logistic regression analysis showed that after adjusted for factors such as age, sex, and comorbidity and found out that comprehensive intervention was correlated with the recurrent positive RT-PCR test results. There was appreciably less recurrence in the comprehensive intervention group.ConclusionsThe factors related to positive RT-PCR test results in observed subjects recovered from COVID-19 were age, comorbidity, and comprehensive intervention, among which comprehensive intervention might be a protective factor.Clinical trial registrationChictr.org.cn, identifier ChiCTR2000030747.
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Project description: Not available
| S-EPMC7328320 | biostudies-literature
Project description:BackgroundSome COVID-19 cases test positive again for SARS-CoV-2 RNA following negative test results and discharge, raising questions about the meaning of virus detection. Better characterization of re-positive cases is urgently needed.MethodsClinical data were obtained through Guangdong's COVID-19 surveillance network. Neutralization antibody titre was determined using microneutralization assays. Potential infectivity of clinical samples was evaluated by cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing.FindingsAmong 619 discharged COVID-19 cases, 87 re-tested as SARS-CoV-2 positive in circumstances of social isolation. All re-positive cases had mild or moderate symptoms at initial diagnosis and were younger on average (median, 28). Re-positive cases (n = 59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n = 218) tested here. No infectious strain could be obtained by culture and no full-length viral genomes could be sequenced from re-positive cases.InterpretationRe-positive SARS-CoV-2 cases do not appear to be caused by active reinfection and were identified in ~14% of discharged cases. A robust NAb response and potential virus genome degradation were detected in almost all re-positive cases, suggesting a substantially lower transmission risk, especially through respiratory routes.
| S-EPMC7444471 | biostudies-literature
Project description:The final months of 2019 witnessed the emergence of a novel coronavirus in the human population. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has since spread across the globe and is posing a major burden on society. Measures taken to reduce its spread critically depend on timely and accurate identification of virus-infected individuals by the most sensitive and specific method available, i.e. real-time reverse transcriptase PCR (RT-PCR). Many commercial kits have recently become available, but their performance has not yet been independently assessed. The aim of this study was to compare basic analytical and clinical performance of selected RT-PCR kits from seven different manufacturers (Altona Diagnostics, BGI, CerTest Biotec, KH Medical, PrimerDesign, R-Biopharm AG, and Seegene). We used serial dilutions of viral RNA to establish PCR efficiency and estimate the 95 % limit of detection (LOD95). Furthermore, we ran a panel of SARS-CoV-2-positive clinical samples (n = 13) for a preliminary evaluation of clinical sensitivity. Finally, we used clinical samples positive for non-coronavirus respiratory viral infections (n = 6) and a panel of RNA from related human coronaviruses to evaluate assay specificity. PCR efficiency was ≥96 % for all assays and the estimated LOD95 varied within a 6-fold range. Using clinical samples, we observed some variations in detection rate between kits. Importantly, none of the assays showed cross-reactivity with other respiratory (corona)viruses, except as expected for the SARS-CoV-1 E-gene. We conclude that all RT-PCR kits assessed in this study may be used for routine diagnostics of COVID-19 in patients by experienced molecular diagnostic laboratories.
| S-EPMC7206434 | biostudies-literature
Project description:Asymptomatic individuals with coronavirus disease (COVID-19) have been identified via nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the epidemiologic characteristics and viral shedding pattern of asymptomatic patients remain largely unknown. In this study, serological testing was applied when identifying nine asymptomatic cases of COVID-19 who showed persistent negative RT-PCR test results for SARS-CoV-2 nucleic acid and no symptoms of COVID-19. Two asymptomatic cases were presumed to be index patients who had cleared the virus when their close contacts developed symptoms of COVID-19. Three of the asymptomatic cases were local individuals who spontaneously recovered before their presumed index patients developed symptoms of COVID-19. This report presents the epidemiologic and clinical characteristics of asymptomatic individuals with SARS-CoV-2 infection that were undetected on RT-PCR tests in previous epidemiologic investigations probably due to the transient viral shedding duration.
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