Articles variably specified sampling sites according to anatomical location, or grouped more than one site for analysis, for example as upper RT Additional file 1 : Table S4. Details of sampling method were generally absent. Two studies specified the person taking the samples. One study described how the nasopharynx was identified and the swab technique length of contact time with the nasopharynx and twisting.
Five studies specified sample storage and transport details. Figures 2 and 3 show the number of positive and negative RT-PCR results for 5-day time intervals since symptom onset and time from hospital admission, respectively. Each panel shows a separate site used in participant sampling. Nasopharyngeal, saliva, and sputum were used where clearly reported. Throat included throat and oropharyngeal. Other URT includes samples reported in articles as nasal, mixed nasal and throat, oral, pharyngeal, or upper respiratory tract.
For pharyngeal sampling, it was not clear if this was nasopharyngeal or oropharyngeal. Other LRT includes sampling reported as lower respiratory tract or one article including pleural fluid sampling. Blood included serum, plasma, or blood. Faeces included stool or anal swab. The total number of tests within a particular time period can be read from the x -axis. The sampling sites yielding the greatest proportion of positive tests were nasopharyngeal, throat, sputum, or faeces.
Insufficient data were available to evaluate saliva and semen. Given that analysis across all participants is likely to be influenced by preferential URT sampling of participants with less severe disease, we also analysed participants who underwent both URT and LRT sampling.
Data based on time since hospital admission are consistent with data for time since symptom onset. Comparison of duration of detectable virus from upper and lower respiratory tract sampling. All samples in review.
Restricted to participants with both sampling methods. Scatterplot where each dot represents a single participant, with the time to undetectable virus with both upper and lower respiratory tract sampling shown for each participant. The time to RT-PCR tests becoming undetectable varied greatly by participant, although time to undetectable virus was similar for both sampling sites Fig.
Comparison of days to undetectable virus from respiratory tract and faecal sampling. Time to undetectable virus in faecal compared to any respiratory tract sample in participants who were tested with both sampling. Scatterplot where each dot represents a single participant, with the time to undetectable virus with both faecal and respiratory tract sampling shown for each participant. Thirty percent of participants tested at both sampling sites do not have detectable virus in faecal samples.
Many articles reported intermittent false negative RT-PCR test results for participants within the monitoring time span. Where participant viral loads were reported, several different profiles were distinguished; two examples are shown in Fig.
Intermittent false negative results were reported either where the level of virus is close to the limit of detection, or in participants with high viral load but for unclear reasons. Example participants with intermittent false negative results. The proportion of studies with high, low, or unclear ROB for each domain is shown in Fig.
All studies were judged at high ROB. Studies also frequently selected a subset of the participant cohort for longitudinal RT-PCR testing, and only results for these participants were included in the study. Ten studies were judged at unclear ROB for the index test domain as the schedule of testing was based on clinician choice rather than being pre-specified by the study or clinical guidelines, or because the samples used for PCR testing were not pre-specified.
Eleven studies were judged at high ROB for the flow and timing domain mainly because continued testing was influenced by easy access to participants, such as by continued hospitalisation. For each domain, the percentage of studies by concern for potential risk of bias is shown: low green , unclear yellow , and high red.
Sampling 10 days after symptom onset greatly reduced the chance of a positive test result. There were limited data on new methods of sample collection like saliva in these longitudinal studies. Sputum samples have similar or higher levels of detection to nasopharyngeal sampling, although this may be influenced by preferential sputum sampling in severely ill participants. Viral detection in faecal samples may be useful to establish virus clearance, although as noted, whether RT or faecal samples have longer duration of viral detection varies between participants.
All included studies were judged at high ROB, so results of this review should be interpreted with caution. Table 3 provides an overview of the major methodological limitations and their potential impact on study results. Lack of technical details, for example of how samples are taken and RT-PCR tests performed, limits the applicability of findings to current testing.
Compared to real life, studies were likely to use more invasive sampling methods, use experienced staff to obtain samples, and sample participants in hospital settings where sample handling could be standardised.
Consequently, estimates of test performance are likely to be overestimated compared to real-world clinical use and in community population testing including self-test kits. These limitations have important implications for how testing strategies should be implemented and in particular how a negative RT-PCR test result should be interpreted. The accuracy of RT-PCR testing is limited by sampling sites used, methods, and the need to test as soon as possible from symptom onset in order to detect the virus.
Previous studies have established that in COVID infection, viral loads typically peak just before symptoms and at symptom onset [ 4 ] and estimated false negative test results over time since exposure from upper respiratory tract samples [ 2 ]. To our knowledge, there has been no prior systematic review of RT-PCR using IPD to quantify the percentage of persons tested who are positive and how this varies by time and sampling site.
Understanding the distribution of anatomical sites with detectable virus is clinically relevant, especially given independent viral replication sites in nose and throat using distinct and separate genetic colonies [ 17 ]. Understanding of different patterns of detection and duration of virus detection at different body sites is essential when designing strategies of testing to contain virus spread.
Notably, it is unclear if detection of virus in faeces is important in disease transmission, although faecal infection was shown in SARS and MERS [ 41 ]. This review uses robust systematic review methods to synthesise published literature and identifies overall patterns not possible from individual articles.
Using IPD, we examined data across studies and avoided study-level ecological biases present when using overall study estimates. IPD regarding sample site at different time points during infection is vital because it provides an overview of test performance impossible from individual studies alone.
Synthesised IPD can also substantiate or reject patterns appearing within individual studies. Within-participant paired comparisons of sampling sites also become possible with sufficient data. The main limitation is the risk of bias in the included studies. Although constraints were understandable given the circumstances in which the studies were done, the consequences for validity need to be highlighted.
Poor reporting of sampling methods and sites impaired our ability to distinguish between and report on variability between them. Limitations: Analysis based on heterogenous studies. Authors assumed date of infection was 5 days before symptoms began; possible this estimate was inaccurate for some patients. Sample collection techniques varied across studies. It was not possible to separate false-negative rates by sample type oropharyngeal vs. Nasopharyngeal and endotracheal samples obtained from persons tested between days after symptom onset and incubated on Vero cells.
Key findings: Twenty-six samples Ct was found to be statistically associated with positive culture OR 0. STT was associated with positive culture OR 0. Limitations: Relatively small sample size; not clear how many samples were available by day. No patients were asymptomatic; these results may not be generalizable to this population. Patient recollection was used to determine symptom onset; recall bias is possible.
Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease a cross-sectional study Pasomsub, May Study population: individuals under investigation who attended an acute respiratory infection clinic in Thailand. Individuals were included if they had a travel history from an endemic area of COVID within 14 days or had a history of contact with an individual who was confirmed to have or suspected of having COVID Individuals provided nasopharyngeal swabs, throat swabs, and saliva samples Primary endpoint: To determine the feasibility of saliva specimens to detect SARS-CoV The sensitivity and specificity of the saliva samples were Positive predictive value and negative predictive value were An analysis of the agreement between nasopharyngeal and throat compared to saliva showed a Limitations: Only patients with respiratory symptoms were enrolled; therefore, these results cannot be applied to asymptomatic patients.
Samples taken after day 5 had an average viral load of 3. Limitations: Small sample size. All patients had mild COVID, which may limit the generalizability of findings to patients with moderate-severe disease.
Residents were categorized as symptomatic if they had had at least one new or worsened typical or atypical symptom of COVID in the preceding 14 days. Asymptomatic residents were those who had no symptoms or only stable chronic symptoms e. Presymptomatic residents were those who were asymptomatic at the time of testing but developed symptoms within 7 days after testing. Limitations: This analysis was conducted in skilled nursing residents, which may limit the generalizability of the findings.
Symptom ascertainment in population was difficult, which could have lead to misclassification of patients. Modeled COVID infectiousness profiles from a separate sample of 77 infector—infectee transmission pairs. Primary endpoint: Temporal patterns of viral shedding. Key findings: High viral loads were detected soon after symptom onset, then gradually decreased towards the detection limit by about day There was no difference in viral loads across sex, age groups and disease severity.
Limitations: Patient recollection was used to determine symptom onset; recall bias is possible. Most patients had moderate COVID, which may limit the generalizability of these findings to patients with severe disease. Study population: Retrospective study of 96 hospitalized patients with COVID in China; 22 with mild disease and 74 with severe disease.
In patients with mild disease, viral loads peaked in respiratory samples in the second week from disease onset; in patients with severe disease, viral load continued to be high during the third week of disease. Limitations: Single-center study. Data collected retrospectively, which may have allowed for confounding. Molecular assays can detect influenza viral RNA positive results for a longer duration than other influenza tests e.
Although molecular assays have high sensitivity, negative results can occur in patients with influenza for multiple reasons, so negative molecular assay RT-PCR results may not always exclude a diagnosis of influenza. If clinical suspicion of influenza is high, antiviral treatment should continue in patients with severe illness or at high risk for complications while additional respiratory specimens are collected and further influenza testing is performed.
Factors that can influence influenza testing results are:. However, even with RT-PCR, false negative results can occur due to improper or poor clinical specimen collection or from poor handling of a specimen after collection and before testing. A negative result can also occur by testing a specimen that was collected when the patient is no longer shedding detectable influenza virus. False positive results, although rare, can occur e. Detection of influenza antigen with rapid antibody-based tests after intranasal influenza vaccination FluMist.
Clin Infect Dis. J Clin Virol. J Clin Microbiol. Shedding and immunogenicity of live attenuated influenza vaccine virus in subjects years of age. Pediatr Infect Dis J. Diagn Microbiol Infect Dis.
J Med Microbiol. Performance of rapid influenza H1N1 diagnostic tests: a meta-analysis. Influenza Other Respir Viruses.
Influenza and Other Respiratory Viruses ;9 3
0コメント