Different performance of three point-of-care SARS-CoV-2 antigen detection devices in symptomatic patients and close asymptomatic contacts: a real-life study

ObjectivesPCR on nasopharyngeal exudates, the cornerstone of the detection of SARS-CoV-2, is time-consuming and commonly unavailable at primary health care centres. Detection of viral nucleocapsid antigens using lateral flow point-of-care tests is helpful for the early triage of patients who attend health care facilities.MethodsThis was a prospective study carried out in clinically suspected cases and close asymptomatic contacts who attended a primary care centre (Madrid, Spain) for SARS-CoV-2 detection. Patients were divided into three 300-patient cohorts (n = 200 symptomatic cases and n = 100 close asymptomatic contacts per cohort). Three antigen detection tests (SGTI-Flex COVID-19 Ag, Panbio COVID-19 Ag Rapid Test Device, and GSD NovaGen SARS-CoV-2 Ag Rapid Test) were used and compared. Paired nasopharyngeal exudates were obtained, one swab for PCR and the other for antigen detection. Each antigen detection test was evaluated on one cohort.ResultsAll tests showed invariably 100% specificity. Sensitivity was 68.9% (95% CI: 55.7–80; SGTI-Flex), 71.1% (95% CI: 55.6–83.6; Panbio), and 84.6% (95% CI: 72–93.1; NovaGen) in clinically suspected patients and 84.6% (95% CI: 54.5–98.1), 33.3% (95% CI: 11.8–61.6), and 55.6% (95% CI: 30.7–78.4) in close asymptomatic contacts, respectively. Sensitivity was systematically higher in samples yielding positive PCR results with Ct ≤ 20.DiscussionWe found considerable test-to-test antigen detection variations among patients with clinical suspicion of COVID-19 and close asymptomatic contacts. Negative antigen results, regardless of the test used, should be confirmed by PCR.     

Detection of severe acute respiratory syndrome coronavirus 2 in nasopharynx according to clinical phenotype of affected patients

ObjectivesDuration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the upper respiratory tract is extremely variable, but its relation to disease severity is unknown. We investigated this relation in the 530 000 inhabitants of the northeastern Italian province of Udine.MethodsWe analysed real-time RT-PCR tests for SARS-CoV-2 in upper respiratory specimens conducted at the Virology Laboratory of the University Hospital of Udine, Italy (which serves the whole province) from 1 March to 30 April 2020 Specimens were from positive individuals in four groups characterized by different disease severity (critically ill patients admitted to intensive care units, patients admitted to infectious disease units, symptomatic patients visiting the emergency department and not hospitalized, and asymptomatic individuals tested during contact tracing or screening activities). Duration of viral positivity was assessed from the first positive test to the day of the first of two consecutive negative tests. Univariate and multivariate analyses were conducted to investigate differences in the four groups.ResultsFrom 1 March to 30 April, 39 483 RT-PCR tests for SARS-CoV-2 were conducted on 23 778 individuals, and 974 individuals had a positive test result. Among those with multiple tests (n = 878), mean time to negativity was 23.7 days (standard error 0.3639; median 23, interquartile range 16–30 days). Mean time to negativity was longer in the group admitted to the intensive care unit than in the others, whereas no difference was observed between asymptomatic patients and those with mild disease.ConclusionsDisease control measures should not be adjusted to account for differences in viral shedding according to symptomatic status.     

Evaluation of nested PCR and loop mediated isothermal amplification assay (LAMP) targeting 47 ​kDa gene of Orientia tsutsugamushi for diagnosis of scrub typhus

PurposeDiagnostic testing, in particular early detection, is critical for scrub typhus, as most infected individuals have nonspecific symptoms that are easily confused with dengue and malaria. PCR and LAMP offer an alternative DNA amplification method for detection of Orientia tsutsugamushi. Detection of Orientia tsutsugamushi DNA by targeting the 47-kDa gene using nested PCR and LAMP for diagnosis of scrub typhus.MethodsA cross-sectional study in a tertiary care hospital in central India. The present study was done on a total of 274 patients with fever of five days or more and negative for other causes of fever viz. malaria, dengue and enteric fever. From each patient 5 ​ml of blood samples was collected in EDTA vial for molecular tests (PCR and LAMP) and in plain vial for serological tests (IgM IFA).The data was entered in Excel sheet and 2 ​× ​2 tables were created to find sensitivity, specificity, positive and negative likelihood ratios, disease prevalence, positive and negative predictive values and accuracy.ResultsPCR showed a sensitivity of 29.73% while the sensitivity of LAMP was 16.22%. The specificity of nested PCR and LAMP was very high, 99.58% and 99.16% respectively. The diagnostic accuracy of nested PCR (90.15%) was found to be marginally better than LAMP (87.96%).ConclusionsFor the treatment of scrub typhus, a gene-based diagnostic test would enable earlier and more accurate detection of the causative agents of the disease than serology in admission samples of patients with acute febrile illness in endemic areas.     

Prospective population-level validation of the Abbott ID NOW severe acute respiratory syndrome coronavirus 2 device implemented in multiple settings for testing asymptomatic and symptomatic individuals

ObjectiveDiagnostic evaluation of the ID NOW coronavirus disease 2019 (COVID-19) assay in various real-world settings among symptomatic and asymptomatic individuals.MethodsDepending on the setting, the ID NOW testing was performed using oropharyngeal swabs (OPSs) taken from patients with symptoms suggestive of COVID-19, asymptomatic close contacts, or asymptomatic individuals as part of outbreak point prevalence screening. From January to April 2021, a select number of sites switched from using OPS to combined oropharyngeal and nasal swab (O + NS) for ID NOW testing. For every individual tested, two swabs were collected by a health care worker: one swab (OPS or O + NS) for ID NOW testing and a separate swab (OPS or nasopharyngeal swab) for RT-PCR.ResultsA total of 129 112 paired samples were analysed (16 061 RT-PCR positive). Of these, 81 697 samples were from 42 COVID-19 community collection sites, 16 924 samples were from 69 rural hospitals, 1927 samples were from nine emergency shelters and addiction treatment facilities, 23 802 samples were from six mobile units that responded to 356 community outbreaks, and 4762 O + NS swabs were collected from three community collection sites and one emergency shelter. The ID NOW assay sensitivity was the highest among symptomatic individuals presenting to community collection sites (92.5%; 95% CI, 92.0–93.0%) and the lowest for asymptomatic individuals associated with community outbreaks (73.9%; 95% CI, 69.8–77.7%). Specificity was >99% in all populations tested.DiscussionThe sensitivity of ID NOW severe acute respiratory syndrome coronavirus 2 testing is the highest when used in symptomatic community populations not seeking medical care. Sensitivity and positive predictive value drop by approximately 10% when tested on asymptomatic populations. Using combined oropharyngeal and nasal swabs did not improve the performance of ID NOW assay.     

Universal screening for familial hypercholesterolemia in 2 populations

PurposeIn Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation.MethodsWe analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents.ResultsA total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child–parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472).ConclusionUniversal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy.     

Real-life evaluation of a rapid antigen test (DPP SARS-CoV-2 Antigen) for COVID-19 diagnosis of primary healthcare patients,in the context of the Omicron-dominant wave in Brazil

ObjectivesWe aimed to investigate the real-life performance of the rapid antigen test in the context of a primary healthcare setting, including symptomatic and asymptomatic individuals that sought diagnosis during an Omicron infection wave.MethodsWe prospectively accessed the performance of the DPP SARS-CoV-2 Antigen test in the context of an Omicron-dominant real-life setting. We evaluated 347 unselected individuals (all-comers) from a public testing centre in Brazil, performing the rapid antigen test diagnosis at point-of-care with fresh samples. The combinatory result from two distinct real-time quantitative PCR (RT-qPCR) methods was employed as a reference and 13 samples with discordant PCR results were excluded.ResultsThe assessment of the rapid test in 67 PCR-positive and 265 negative samples revealed an overall sensitivity of 80.5% (CI 95% = 69.1%–89.2%), specificity of 99.2% (CI 95% = 97.3%–99.1%) and positive/negative predictive values higher than 95%. However, we observed that the sensitivity was dependent on the viral load (sensitivity in Ct < 31 = 93.7%, CI = 82.8%–98.7%; Ct > 31 = 47.4%, CI = 24.4%–71.1%). The positive samples evaluated in the study were Omicron (BA.1/BA.1.1) by whole-genome sequencing (n = 40) and multiplex RT-qPCR (n = 17).ConclusionsAltogether, the data obtained from a real-life prospective cohort supports that the rapid antigen test sensitivity for Omicron remains high and underscores the reliability of the test for COVID-19 diagnosis in settings with high disease prevalence and limited PCR testing capability.     

Relevance of cutoff on a 4th generation ELISA performance in the false positive rate during HIV diagnostic in a low HIV prevalence setting

BackgroundDespite the high specificity of fourth-generation enzyme immunoassays (4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value is low in populations with low HIV prevalence. Thus, screening should be optimized to reduce false positive results.ObjectivesThe influence of sample cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the routine HIV diagnosis in a low HIV prevalence population was evaluated.Study designA total of 30,201 sera were tested for HIV diagnosis using Abbott Architect^® HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months. Architect S/CO values were recorded, comparing the HIV-1 positive results following Architect interpretation (S/CO ≥ 1) with the final HIV-1 diagnosis by confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC curve was also performed.ResultsAmong the 30,201 HIV performed tests, 256 (0.85%) were positive according to Architect interpretation (S/CO ≥ 1) but only 229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27 (10.5%) of 256 samples with S/CO ≥ 1 by Architect were false positive diagnose. The false positive rate decreased when the S/CO ratio increased. All 19 samples with S/CO ≤10 were false positives and all 220 with S/CO > 50 true HIV-positives. The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative results were found.ConclusionsWe show that very low S/CO values during HIV-1 screening using Architect can result HIV negative after confirmation by LIA and NAT. The false positive rate is reduced when S/CO increases.     

Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-19) in a Fangcang Hospital

ObjectivesTo describe the clinical characteristics of patients in a Fangcang Hospital.MethodsNon-critically ill individuals with positive SARS-CoV-2 RT-PCR tests admitted between 7 February and 12 February 2020 to Dongxihu Fangcang Hospital, which was promptly constructed because of the rapid, exponential increase in COVID-19 patients in Wuhan, China, were included; clinical course through to 22 February was recorded.ResultsA total of 1012 non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests were included in the study. Thirty (of 1012, 3.0%) individuals were asymptomatic on admission. During hospitalization, 16 of 30 (53.3%) asymptomatic individuals developed different symptoms. Fourteen of 1012 patients (1.4%) remained asymptomatic from exposure to the end of follow up, with a median duration of 24 days (interquartile range 22–27). Fever (761 of 1012, 75.2%) and cough (531 of 1012, 52.4%) were the most common symptoms. Small patchy opacities (355 of 917, 38.7%) and ground-glass opacities (508 of 917, 55.4%) were common imaging manifestations in chest CT scans. One hundred patients (9.9%) were transferred to designated hospitals due to aggravation of illness. Diarrhoea emerged in 152 of 1012 patients (15.0%). Male, older age, diabetes, cardiovascular diseases, chills, dyspnoea, So₂ value of ≤93%, white blood cell counts of >10 × 10⁹/L and large consolidated opacities on CT images were all risk factors for aggravation of illness.ConclusionsNon-critically ill individuals had different clinical characteristics from critically ill individuals. Asymptomatic infections only accounted for a small proportion of COVID-19. Although with a low incidence, diarrhoea was observed in patients with COVID-19, indicating the possibility of faecal–oral transmission.     

Evaluation of a rapid antigen test (Panbio™ COVID-19 Ag rapid test device) for SARS-CoV-2 detection in asymptomatic close contacts of COVID-19 patients

ObjectivesThere is limited information on the performance of rapid antigen detection (RAD) tests to identify SARS-CoV-2-infected asymptomatic individuals. In this field study, we evaluated the Panbio? COVID-19 Ag Rapid Test Device (Abbott Diagnostics, Jena, Germany) for this purpose.MethodsA total of 634 individuals (355 female; median age, 37 years; range, 9–87) were enrolled. Two nasopharyngeal swabs were collected from household (n = 338) and non-household contacts (n = 296) of COVID-19 cases. RAD testing was carried out at the point of care. The RT-PCR test used was the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MA, USA).ResultsHousehold contacts were tested at a median of 2 days (range, 1–7) after diagnosis of the index case, whereas non-household contacts (n = 296) were tested at a median of 6 days (range, 1–7) after exposure. In total, 79 individuals (12.4%) tested positive by RT-PCR, of whom 38 (48.1%) yielded positive RAD results. The overall sensitivity and specificity of the RAD test was 48.1% (95% CI 37.4–58.9) and 100% (95% CI 99.3–100), respectively. Sensitivity was higher in household (50.8%; 95% CI 38.9–62.5) than in non-household (35.7%; 95% CI 16.3–61.2%) contacts. Individuals testing positive by RAD test were more likely (p < 0.001) to become symptomatic than their negative counterparts.DiscussionThe Panbio test displays low sensitivity in asymptomatic close contacts of COVID-19 patients, particularly in non-household contacts. Nonetheless, establishing the optimal timing for upper respiratory tract collection in this group seems imperative to pinpoint test sensitivity.     

The importance of anosmia,ageusia and age in community presentation of symptomatic and asymptomatic SARS-CoV-2 infection in Louisiana,USA; a cross-sectional prevalence study

ObjectiveWhile many seroprevalence studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed, few are demographically representative. This investigation focused on defining the nature and frequency of symptomatic and asymptomatic SARS-CoV-2 infection in a representative, cross-sectional sample of communities in Louisiana, USA.MethodsA sample of 4778 adults from New Orleans and Baton Rouge, Louisiana were given a survey of symptoms and co-morbidities, nasopharyngeal swab to test for active infection (PCR), and blood draw to test for past infection (IgG). Odds ratios, cluster analysis, quantification of virus and antibody, and linear modelling were used to understand whether certain symptoms were associated with a positive test, how symptoms grouped together, whether virus or antibody varied by symptom status, and whether being symptomatic was different across the age span.ResultsReported anosmia/ageusia was strongly associated with a positive test; 40.6% (93/229) tested positive versus 4.8% (218/4549) positivity in those who did not report anosmia/ageusia (OR 13.6, 95% CI 10.1–18.3). Of the people who tested positive, 47.3% (147/311) were completely asymptomatic. Symptom presentation clustered into three groups; low/no symptoms (0.4 ± 0.9, mean ± SD), highly symptomatic (7.5 ± 1.9) or moderately symptomatic (4.0 ± 1.5). Quantity of virus was lower in the asymptomatic versus symptomatic group (cycle number 23.3 ± 8.3 versus 17.3 ± 9.0; p < 0.001). Modelling the probability of symptoms showed changes with age; the highest probability of reporting symptoms was 64.6% (95% CI 50.4–76.5) at age 29 years, which decreased to a probability of 49.3% (95% CI 36.6–62.0) at age 60 years and only 25.1% (95% CI 5.0–68.1) at age 80 years.ConclusionAnosmia/ageusia can be used to differentiate SARS-CoV-2 infection from other illnesses, and, given the high ratio of asymptomatic individuals, contact tracing should include those without symptoms. Regular testing in congregant settings of those over age 60 years may help mitigate asymptomatic spread.     

Asymptomatic Clostridium difficile carriage rate post-fecal microbiota transplant is low: a prospective clinical and stool assessment

ObjectivesWe aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT).MethodsAll patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8 weeks post FMT. Assessments occurred at 1 week and 4 weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well.Results167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C. difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129).ConclusionsAsymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary.     

Evolving strategy for HCV testing in an Italian tertiary care hospital

BackgroundDiagnostic tests for hepatitis C virus (HCV) infection should be adapted according to the clinical status of the patient.ObjectivesWe exploited the application of different HCV diagnostic algorithms in a tertiary care hospital practice.Study designThe laboratory clinical reports to the medical orders for HCV testing during three years were clustered by different combinations of assays for anti-HCV antibodies (HCV Ab) (screening and confirmatory), HCV nucleic acid (HCV-RNA), HCV core antigen (HCV Ag). The latter was the first-line assay in acute HCV infections requiring a rapid assessment of the infectious state.ResultsThe majority (91.9%) of the 2726 subjects whose samples were analyzed were inpatients. Most of the patients/subjects were tested for clinical suspicion of viral hepatitis (49.2%), or occupational accident to health care professionals (20.0%). On 66% of samples HCV Ag test alone was performed and resulted positive in 116 cases (6%), while it was detected in 50.3% of anti-HCV positive samples. The agreement between HCV Ag and HCV-RNA was very high (k = 0.97); HCV Ag positivity rates increased according to the signal of the HCV Ab screening test.ConclusionsThe use of different testing strategies according to the patients’ history and clinical status allowed a significant reduction of the number of tests performed and the time needed to provide a diagnostic response useful for patients’ management without compromising the overall diagnostic accuracy for HCV infection.     

Prenatal reflex DNA screening for trisomies 21, 18, and 13

PurposeThe purpose of the study was to determine the screening performance of prenatal reflex DNA screening for trisomies 21 (T21), 18 (T18), and 13 (T13) as part of a routine service at five hospitals.MethodsWomen who accepted screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age). Those with a risk of having an affected pregnancy ≥1 in 800 were reflexed to a DNA sequencing test using stored plasma from the original blood sample, thereby avoiding the need to recall them.ResultsOf 22,812 women screened (including 106 with affected pregnancies), 2,480 (10.9%) were reflexed to DNA testing; 101/106 were detected (69/73 T21, 24/25 T18, and 8/8 T13), a 95% detection rate (95% confidence interval 89–98%) with four false positives (0.02%, 95% confidence interval 0.00–0.05%). The odds of being affected given a positive result were 25:1. Of the 105 screen-positive pregnancies, 91 (87%) had an invasive diagnostic test. Reflex DNA screening avoided up to 530 invasive diagnostic tests compared with using the combined test.ConclusionReflex DNA screening was successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of screening.     

Head-to-head comparison of the diagnostic accuracies of BD Veritor™ System RSV and Quidel® Sofia® RSV FIA systems for respiratory syncytial virus (RSV) diagnosis

BackgroundRespiratory syncytial virus (RSV) is one of the most common causes of severe lower respiratory tract disease among infants and young children. BD Veritor™ System RSV (BD) and Quidel^® Sofia^® RSV FIA (QD) are the new generation lateral flow digital immunoassay (DIA) tests with an instrumented read for the qualitative detection of RSV viral antigens.ObjectiveTo compare the diagnostic accuracies of BD and QD for RSV detection using fresh nasopharyngeal aspirates and nasopharyngeal swab specimens collected in universal transport media during 2013–2014 respiratory season.Study designThe two DIA tests were performed simultaneously on randomly selected specimens on a weekly basis during the RSV season until 200 fresh remnant specimens were enrolled. Real-time RT-PCR assay results were used to compare and evaluate the performance of both RSV DIA assays.ResultsAmong 200 specimens tested, RSV real-time RT-PCR assay detected RSV in 104 samples, while QD detected 84 samples and BD detected 74 samples as positive. The overall sensitivity for detection of RSV in comparison to PCR was 71.15% (61.3–79.4) for BD and 80.77% (71.6–87.6) for QD system (P = 0.36). The specificity was 100% (95.2–100) for both systems. The work flow analysis revealed that the overall specimen processing time was significantly lower for BD as compared with the QD assay.ConclusionsIn comparison with the real-time PCR, the QD system showed a higher sensitivity than that of the BD system, but the difference did not reach statistical significance (P = 0.36). Both BD and QD systems were found comparable in terms of specificity.     

A diversified approach for PKU treatment: Routine screening yields high incidence of psychiatric distress in phenylketonuria clinics

ObjectivesIndividuals with phenylketonuria (PKU) treated early and continuously are reported to have psychiatric and executive function impairments. The feasibility of screening for psychiatric distress and executive function impairment in individuals with PKU was tested in 3 separate clinics in North America.MethodsIndividuals were offered screening for psychiatric distress using the Pediatric Symptom Checklist, the PSC–Youth Report or the Brief Symptom Inventory and executive function impairment using the Behavior Rating Inventory of Executive Function. Gender, age and blood phenylalanine (Phe) concentrations obtained most recently and during the 2 years prior to screening were assessed.ResultsMore than 90% of patients with PKU accepted the screening for psychiatric distress during their routine clinic visit. The screening took 15–20 min. 32% of patients screened positive for psychiatric distress and 19% for executive function impairment. More individuals > 18 years screened positive for psychiatric distress while a similar number screened positive for executive function impairment across age groups. Lower blood Phe levels correlated with negative screening for psychiatric distress. Patients positive for psychiatric distress had higher (p = 0.009) median and most recent blood Phe values (p = 0.05).Discussion/conclusionsRoutine screening for psychiatric distress of patients with phenylketonuria could be easily implemented in current clinic structures. High incidences of positive screens reinforce the need for regular psychiatric assessments of individuals with PKU. Identification and referral to local mental health providers might help to improve the standard of care for individuals with PKU.     

Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review

BackgroundAcute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment.ObjectiveTo assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology.Data sourcesMEDLINE, Embase and Web of Science databases were searched to February 2021.Study eligibility criteriaDiagnostic accuracy studies comparing accuracy of point-of-care and rapid diagnostic tests in primary or secondary care, consisting of biomarker combinations, to identify bacterial or viral aetiology of RTI.MethodsRisk of bias was assessed using the QUADAS-2 tool. Sensitivity and specificity of tests reported by more than one study were meta-analysed using a random effects model.ResultsTwenty observational studies (3514 patients) were identified. Eighteen were judged at high risk of bias. For bacterial aetiologies, sensitivity ranged from 61% to 100% and specificity from 18% to 96%. For viral aetiologies, sensitivity ranged from 59% to 97% and specificity from 74% to 100%. Studies evaluating two commercial tests were meta-analysed. For ImmunoXpert, the summary sensitivity and specificity were 85% (95% CI 75%–91%, k = 4) and 86% (95% CI 73%–93%, k = 4) for bacterial infections, and 90% (95% CI 79%–96%, k = 3) and 92% (95% CI 83%–96%, k = 3) for viral infections, respectively. FebriDx had pooled sensitivity and specificity of 84% (95% CI 75%–90%, k = 4) and 93% (95% CI 90%–95%, k = 4) for bacterial infections, and 87% (95% CI 72%–95%; k = 4) and 82% (95% CI 66%–86%, k = 4) for viral infections, respectively.ConclusionCombinations of biomarkers show potential clinical utility in discriminating the aetiology of RTIs. However, the limitations in the evidence base, due to a high proportion of studies with high risk of bias, preclude firm conclusions. Future research should be in primary care and evaluate patient outcomes and cost-effectiveness with experimental study designs.Clinical trialPROSPERO registration number: CRD42020178973.     

Impact of rapid influenza diagnostic test on physician estimation of viral infection probability in paediatric emergency department during epidemic period

BackgroundThe clinical diagnosis of influenza is difficult in the younger children.ObjectivesEvaluate the impact of rapid influenza diagnostic test (RIDT) on clinicians’ estimation of the clinical probability of influenza in children.Study designThis prospective study included children aged from 1 month to 5 years who were admitted in a university paediatric emergency department during an influenza epidemic period and presented with fever without source. The RIDT Quickvue^® was performed on nasopharyngeal aspiration and results were confirmed with immunofluorescence and/or PCR. The clinical probability of influenza and serious bacterial infection (SBI) was evaluated for each child before and after the physician(s) was informed of the RIDT results.Results170 children were included from January 15th through March 18th, 2013. After the only clinical examination, the overall clinical probability of influenza was 66.0% [CI 95%: 63.04–68.4], and was significantly increased at 92.4% [CI 95%: 89.5–95.3] in case of positive RIDT and significantly decreased at 30.8% [CI 95%: 29.0–32.5] in case of negative RIDT without knowing the results of laboratory tests. Whereas the initial clinical probability of influenza were appropriate regarding the prevalence (66.0% vs. 57.0%), the probability of SBI was overestimated (30.2% vs. 8.8%). The RIDT result positive enabled a significant decrease in orders for chest X-rays (64,4% vs. 45.8%, p < 0,05) and laboratory tests (71,1% vs. 41.1%, p < 0,05).ConclusionsThe RIDT seems to be a useful diagnostic tool for ED clinicians in epidemic conditions. Improving clinician estimation of flu probability would reduce orders for imaging and testing.