LitCovid-sentences  

PMC:7386785 / 59507-68918 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T530 0-10 Sentence denotes Discussion
T531 12-35 Sentence denotes Summary of main results
T532 36-312 Sentence denotes Individual signs and symptoms appear to have very poor diagnostic properties for COVID‐19, although this has to be interpreted in the presence of a limited number of studies, heterogeneity between the studies precluding any firm conclusions and in a context of selection bias.
T533 313-392 Sentence denotes Most features had very low sensitivity, while specificity was moderate to high.
T534 393-639 Sentence denotes We have identified four possible red flags, that is, symptoms that increased the probability of COVID‐19 when present because of a positive likelihood ratio of at least 5 in at least one study: fever, myalgia or arthralgia, fatigue, and headache.
T535 640-847 Sentence denotes When we apply the results of sensitivity and specificity of these systemic features to disease probabilities, we assess their value to rule in and rule out disease as shown in the dumbbell plots (Figure 16).
T536 848-939 Sentence denotes These clearly show the limited effect on disease probability from these signs and symptoms.
T537 940-1057 Sentence denotes Importantly, we did not find any studies investigating the diagnostic accuracy of combinations of signs and symptoms.
T538 1058-1122 Sentence denotes There were also no studies from community primary care settings.
T539 1123-1376 Sentence denotes Some of our findings are counterintuitive, for example that the majority of the studies that investigated cough found that cough decreases the probability of COVID‐19 despite the fact that it is part of the case definition of COVID‐19 in most countries.
T540 1377-1526 Sentence denotes This is also the case for fever in two studies and myalgia in one study ‐ even though these features were also red flags in at least one other study.
T541 1527-1575 Sentence denotes We believe this may be caused by selection bias.
T542 1576-1945 Sentence denotes Selection bias is present when selective and non‐random inclusion and exclusion of participants apply and the resulting association between exposure and outcome (here the accuracy of the test) differs in the selected study population compared to the eligible study population, and it has been shown that this may decrease estimates of diagnostic accuracy (Rutjes 2006).
T543 1946-2105 Sentence denotes For the diagnosis of COVID‐19, rapidly and constantly changing, and widely variable test criteria have influenced who was referred for testing and who was not.
T544 2106-2314 Sentence denotes Inclusion in the study of only a selective fraction of eligible patients can give a biased estimate of the real accuracy of the index test when measured against the reference standard and real disease status.
T545 2315-2435 Sentence denotes Griffith 2020 reported on the problematic presence of collider stratification bias in the published studies on COVID‐19.
T546 2436-2656 Sentence denotes Appropriate sampling strategies need to be applied to avoid conclusions of spurious relationships, more specifically in our case, the biased accuracy estimates of signs and symptoms for the diagnosis of COVID‐19 disease.
T547 2657-2897 Sentence denotes Selection of patients based on the presence of specific pre‐set symptoms, such as fever and cough, lead to biased associations between these symptoms and disease, and sensitivity and specificity estimates that differ from their true values.
T548 2898-2965 Sentence denotes The example of collider bias for cough is illustrated in Figure 17.
T549 2966-3179 Sentence denotes Grouping studies by diagnostic criteria for selection might clarify this issue, but studies do not clearly describe them, with study authors referring to the guidelines in general that were applicable at the time.
T550 3180-3384 Sentence denotes 17 Directed acyclic graph on cough Another form of selection bias is spectrum bias, where the patients included in the studies do not reflect the patient spectrum to which the index test will be applied.
T551 3385-3582 Sentence denotes The inclusion of hospitalised patients can lead to such a bias, when in these patients both the distribution of signs and symptoms differ and assessment with the reference standard is differential.
T552 3583-3752 Sentence denotes In addition, the distribution and severity of alternative diagnoses may be different in hospitalised populations than in patients presenting to ambulatory care settings.
T553 3754-3792 Sentence denotes Strengths and weaknesses of the review
T554 3793-3998 Sentence denotes Strengths of our review are the systematic and broad search performed to include all possible studies, including those prior to peer‐review, to gather the largest number of studies available at this point.
T555 3999-4290 Sentence denotes Exclusion of cases‐only studies, the largest number of the published cohorts of patients with COVID‐19, limits the available data but also improves the quality of the evidence and the possibility to present both sensitivity and specificity (cases only cannot provide both accuracy measures).
T556 4291-4436 Sentence denotes Because this is a living systematic review, future updates may offer the possibility to do a meta‐analysis, which was not possible at this stage.
T557 4437-4608 Sentence denotes In addition, further insights into this novel disease may lead to new evidence on signs and symptoms that are more diagnostic, which we will incorporate in future updates.
T558 4609-4693 Sentence denotes The lack of data on combinations of signs and symptoms is an important evidence gap.
T559 4694-4837 Sentence denotes Consequently, there is no evidence on syndromic presentation and the value of composite signs and symptoms on the diagnostic accuracy measures.
T560 4838-4941 Sentence denotes In addition, subgroup analyses by the pre‐defined variables were not feasible due to lack of reporting.
T561 4942-5042 Sentence denotes We need to assess multiple variables for their possible confounding effect on the summary estimates.
T562 5043-5290 Sentence denotes Possible confounders include the presence of other respiratory pathogens (seasonality), the phase of the epidemic, exposure to high versus low prevalence setting, high or low exposure risk, comorbidity of the participants, or time since infection.
T563 5291-5542 Sentence denotes Seasonality may influence specificity, because alternative diagnoses such as influenza or other respiratory viruses are more prevalent in winter, leading to more non‐COVID‐19 patients displaying symptoms such as cough or fever, decreasing specificity.
T564 5543-5672 Sentence denotes In this version of the review, all studies were conducted in Winter or early Spring, suggesting this may still have been at play.
T565 5673-5952 Sentence denotes However, social distancing policies have shortened this year's influenza season in several countries (www.who.int/influenza/surveillance_monitoring/updates/en/), which may have led to higher specificity for signs and symptoms than what we may expect in the next influenza season.
T566 5953-6036 Sentence denotes In future updates of the review, we will explore seasonality effects if data allow.
T567 6037-6218 Sentence denotes As for time since onset, given that the moment of infection is more likely than not an unrecognisable and unmeasurable variable, time since onset of symptoms can be used as a proxy.
T568 6219-6454 Sentence denotes Reporting of studies, with presentation of the 2x2 table stratified by time since onset of disease, is informative and might have the potential to increase accuracy of the signs and symptoms and their diagnostic differential potential.
T569 6456-6504 Sentence denotes Applicability of findings to the review question
T570 6505-6896 Sentence denotes The high risk of selection bias, with many studies including patients who had already been admitted to hospital or who presented to hospital settings with the intent to hospitalise, leads to findings that are less applicable to people presenting in primary care, who on average experience a shorter illness duration, less severe symptoms and have a lower probability of the target condition.
T571 6897-6961 Sentence denotes Our search did not find any articles providing data on children.
T572 6962-7048 Sentence denotes Children have been underrepresented in the studies on diagnosing SARS‐CoV‐2 infection.
T573 7049-7226 Sentence denotes Their absence seems related to the general mild presentation of the disease in the paediatric population, and the even more frequent asymptomatic course of COVID‐19 in children.
T574 7227-7301 Sentence denotes The full scope of disease presentation in children is therefore not known.
T575 7302-7622 Sentence denotes It is important to identify signs and symptoms that can be used to clinically assess children with suspected COVID‐19, especially because aspecific presentations and fever without a source are already common in this age group, and acute infection in children is a common cause for families to self‐isolate or get tested.
T576 7623-7870 Sentence denotes Misclassification of children, where children will be asked to remain in quarantine when they present with predefined, but not yet evidence‐based symptoms needs to be avoided to decrease the possible damage done to children's health and education.
T577 7871-7990 Sentence denotes Having separate data for neonates, young infants, toddlers, school‐aged children and adolescents is therefore of value.
T578 7991-8039 Sentence denotes Another important patient group is older adults.
T579 8040-8209 Sentence denotes They are most at risk of an adverse outcome of SARS‐CoV‐2 infection, including an increased risk of requiring intensive care support and and increased risk of mortality.
T580 8210-8294 Sentence denotes In this version of the review, only one study focused on adults aged 55 to 75 years.
T581 8295-8401 Sentence denotes All other studies included adults of all ages and did not present results separately for older age groups.
T582 8402-8676 Sentence denotes The lack of a solid evidence base for the diagnosis of COVID‐19 in older adults adds to the difficulty in diagnosing serious infections in this age group, as other serious infections such as bacterial pneumonia or urinary sepsis also tend to lead to aspecific presentations.
T583 8677-8818 Sentence denotes The association of a single sign or symptom with COVID‐19 is highly uncertain, and we do not have data on combinations of signs and symptoms.
T584 8819-8985 Sentence denotes Additionally, potentially more diagnostic symptoms such as loss of sense of smell have not yet been studied widely and remain to be assessed in well designed studies.
T585 8986-9215 Sentence denotes Moreover, the nature of the signs and symptoms that are used to guide self‐isolation decisions are such that people may end up being quarantined on a regular basis, leading to missed days at school or work, isolation and anxiety.
T586 9216-9411 Sentence denotes In future updates of this review, we intend to organise findings by age group, settings (in particular primary care settings versus hospital settings), and target condition, when evidence allows.