Routine laboratory testing to determine if a patient has COVID-19.

BACKGROUND: Specific diagnostic tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting COVID-19 disease are not always available and take time to obtain results. Routine laboratory markers such as white blood cell count, measures of anticoagulation, C-reactive protein (CRP) and procalcitonin, are used to assess the clinical status of a patient. These laboratory tests may be useful for the triage of people with potential COVID-19 to prioritize them for different levels of treatment, especially in situations where time and resources are limited. OBJECTIVES: To assess the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. SEARCH METHODS: On 4 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: We included both case-control designs and consecutive series of patients that assessed the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. The reference standard could be reverse transcriptase polymerase chain reaction (RT-PCR) alone; RT-PCR plus clinical expertise or and imaging; repeated RT-PCR several days apart or from different samples; WHO and other case definitions; and any other reference standard used by the study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each included study. They also assessed the methodological quality of the studies, using QUADAS-2. We used the 'NLMIXED' procedure in SAS 9.4 for the hierarchical summary receiver operating characteristic (HSROC) meta-analyses of tests for which we included four or more studies. To facilitate interpretation of results, for each meta-analysis we estimated summary sensitivity at the points on the SROC curve that corresponded to the median and interquartile range boundaries of specificities in the included studies. MAIN RESULTS: We included 21 studies in this review, including 14,126 COVID-19 patients and 56,585 non-COVID-19 patients in total. Studies evaluated a total of 67 different laboratory tests. Although we were interested in the diagnotic accuracy of routine tests for COVID-19, the included studies used detection of SARS-CoV-2 infection through RT-PCR as reference standard. There was considerable heterogeneity between tests, threshold values and the settings in which they were applied. For some tests a positive result was defined as a decrease compared to normal vaues, for other tests a positive result was defined as an increase, and for some tests both increase and decrease may have indicated test positivity. None of the studies had either low risk of bias on all domains or low concerns for applicability for all domains. Only three of the tests evaluated had a summary sensitivity and specificity over 50%. These were: increase in interleukin-6, increase in C-reactive protein and lymphocyte count decrease. Blood count Eleven studies evaluated a decrease in white blood cell count, with a median specificity of 93% and a summary sensitivity of 25% (95% CI 8.0% to 27%; very low-certainty evidence). The 15 studies that evaluated an increase in white blood cell count had a lower median specificity and a lower corresponding sensitivity. Four studies evaluated a decrease in neutrophil count. Their median specificity was 93%, corresponding to a summary sensitivity of 10% (95% CI 1.0% to 56%; low-certainty evidence). The 11 studies that evaluated an increase in neutrophil count had a lower median specificity and a lower corresponding sensitivity. The summary sensitivity of an increase in neutrophil percentage (4 studies) was 59% (95% CI 1.0% to 100%) at median specificity (38%; very low-certainty evidence). The summary sensitivity of an increase in monocyte count (4 studies) was 13% (95% CI 6.0% to 26%) at median specificity (73%; very low-certainty evidence). The summary sensitivity of a decrease in lymphocyte count (13 studies) was 64% (95% CI 28% to 89%) at median specificity (53%; low-certainty evidence). Four studies that evaluated a decrease in lymphocyte percentage showed a lower median specificity and lower corresponding sensitivity. The summary sensitivity of a decrease in platelets (4 studies) was 19% (95% CI 10% to 32%) at median specificity (88%; low-certainty evidence). Liver function tests The summary sensitivity of an increase in alanine aminotransferase (9 studies) was 12% (95% CI 3% to 34%) at median specificity (92%; low-certainty evidence). The summary sensitivity of an increase in aspartate aminotransferase (7 studies) was 29% (95% CI 17% to 45%) at median specificity (81%) (low-certainty evidence). The summary sensitivity of a decrease in albumin (4 studies) was 21% (95% CI 3% to 67%) at median specificity (66%; low-certainty evidence). The summary sensitivity of an increase in total bilirubin (4 studies) was 12% (95% CI 3.0% to 34%) at median specificity (92%; very low-certainty evidence). Markers of inflammation The summary sensitivity of an increase in CRP (14 studies) was 66% (95% CI 55% to 75%) at median specificity (44%; very low-certainty evidence). The summary sensitivity of an increase in procalcitonin (6 studies) was 3% (95% CI 1% to 19%) at median specificity (86%; very low-certainty evidence). The summary sensitivity of an increase in IL-6 (four studies) was 73% (95% CI 36% to 93%) at median specificity (58%) (very low-certainty evidence). Other biomarkers The summary sensitivity of an increase in creatine kinase (5 studies) was 11% (95% CI 6% to 19%) at median specificity (94%) (low-certainty evidence). The summary sensitivity of an increase in serum creatinine (four studies) was 7% (95% CI 1% to 37%) at median specificity (91%; low-certainty evidence). The summary sensitivity of an increase in lactate dehydrogenase (4 studies) was 25% (95% CI 15% to 38%) at median specificity (72%; very low-certainty evidence). AUTHORS' CONCLUSIONS: Although these tests give an indication about the general health status of patients and some tests may be specific indicators for inflammatory processes, none of the tests we investigated are useful for accurately ruling in or ruling out COVID-19 on their own. Studies were done in specific hospitalized populations, and future studies should consider non-hospital settings to evaluate how these tests would perform in people with milder symptoms.

A pilot randomized trial of incentive strategies to promote HIV retesting in rural Uganda.

BACKGROUND: Retesting for HIV is critical to identifying newly-infected persons and reinforcing prevention efforts among at-risk adults. Incentives can increase one-time HIV testing, but their role in promoting retesting is unknown. We sought to test feasibility and acceptability of incentive strategies, including commitment contracts, to promote HIV retesting among at-risk adults in rural Uganda. METHODS: At-risk HIV-negative adults were enrolled in a pilot trial assessing feasibility and acceptability of incentive strategies to promote HIV retesting three months after enrollment. Participants were randomized (1:1:3) to: 1) no incentive; 2) standard cash incentive (~US$4); and 3) commitment contract: participants could voluntarily make a low- or high-value deposit that would be returned with added interest (totaling ~US$4 including the deposit) upon retesting or lost if participants failed to retest. Contracts sought to promote retesting by leveraging loss aversion and addressing present bias via pre-commitment. Outcomes included acceptability of trial enrollment, contract feasibility (proportion of participants making deposits), and HIV retesting uptake. RESULTS: Of 130 HIV-negative eligible adults, 123 (95%) enrolled and were randomized: 74 (60%) to commitment contracts, 25 (20%) to standard incentives, and 24 (20%) to no incentive. Of contract participants, 69 (93%) made deposits. Overall, 93 (76%) participants retested for HIV: uptake was highest in the standard incentive group (22/25 [88%]) and lowest in high-value contract (26/36 [72%]) and no incentive (17/24 [71%]) groups. CONCLUSION: In a randomized trial of strategies to promote HIV retesting among at-risk adults in Uganda, incentive strategies, including commitment contracts, were feasible and had high acceptability. Our findings suggest use of incentives for HIV retesting merits further comparison in a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT:02890459.

Leveraging incentives to increase HIV testing uptake among men: qualitative insights from rural Uganda.

BACKGROUND: Few studies have explored how economic incentives influence behavioral outcomes. This study aimed to identify pathways of action of an incentives-based intervention to increase men's participation in HIV testing. METHODS: The qualitative study was embedded in a randomized-controlled trial that compared effectiveness of gain-framed, loss-framed and lottery-based incentives to increase HIV testing among men. Following testing at a community health campaign, 60 in-depth interviews were conducted with men systematically sampled on the basis of age, incentive group, and campaign attendance. Data were coded deductively and inductively for thematic content analysis. RESULTS: Incentives addressed men's structural, interpersonal and individual-level barriers to testing: offered at convenient locations, incentives offset costs of testing, in lost wages, which are exacerbated when livelihoods required mobility. Interpersonal barriers included anticipated stigma/fear of disclosure, social obligations, and negative peer influences. Providing incentives in public settings provided "social proof" that prizes could be won, and facilitated social support and positive norms by promoting testing with trusted others. Incentives had little influence when men appraised prize values to be low, disbelieved they would win a prize, or were already intrinsically motivated to test. Yet, incentives provided a behavioral 'cue to action' for many men who perceived themselves to be susceptible to HIV and perceived HIV disease to be severe, acting as secondary motivator for testing that "sweetened the deal". CONCLUSION: Incentives can be an important 'lever' to promote men's healthy behaviors in resource-poor settings. HIV testing in convenient, public settings, when paired with incentives, provides multiple pathways to stimulate men's testing uptake. TRIAL REGISTRATION: Registered with ClinicalTrials.gov on 08/10/2016, ID: NCT02890459. The first participant was enrolled on 11th April 2016.

Comparative effectiveness of novel nonmonetary incentives to promote HIV testing.

OBJECTIVE: To assess the comparative effectiveness of alternative incentive-based interventions to promote HIV testing among men. DESIGN: Randomized clinical trial. METHODS: We enumerated four Ugandan parishes and enrolled men at least 18 years. Participants were randomized to six groups that received incentives of varying type and amount for HIV testing at a 13-day community health campaign. Incentive types were: gain-framed (control): participants were told they would receive a prize for testing; loss-framed: participants were told they had won a prize, shown several prizes, asked to select one, then told they would lose the prize if they did not test; lotteries: those who tested had a chance to win larger prizes. Each incentive type had a low and high amount (∼US$1 and US$5/participant). The primary outcome was HIV-testing uptake at the community health campaign. RESULTS: Of 2532 participants, 1924 (76%) tested for HIV; 7.6% of those tested were HIV-positive. There was no significant difference in testing uptake in the two lottery groups (78%; P = 0.076) or two loss-framed groups (77%; P = 0.235) vs. two gain-framed groups (74%). Across incentive types, testing did not differ significantly in high-cost (76%) vs. low-cost (75%; P = 0.416) groups. Within low-cost groups, testing uptake was significantly higher in the lottery (80%) vs. gain-framed (72%; P = 0.009) group. CONCLUSION: Overall, neither offering incentives via lotteries nor framing incentives as losses resulted in significant increases in HIV testing compared with standard gain-framed incentives. However, when offering low-cost incentives to promote HIV testing, providing lottery-based rewards may be a better strategy than gain-framed incentives.