Evaluating a SARS-CoV-2 screening strategy based on serological tests.

BACKGROUND: facing the SARS-CoV-2 epidemic requires intensive testing on the population to early identify and isolate infected subjects. Although RT-PCR is the most reliable technique to detect ongoing infections, serological tests are frequently proposed as tools in heterogeneous screening strategies. OBJECTIVES: to analyse the performance of a screening strategy proposed by the local government of Tuscany (Central Italy), which first uses qualitative rapid tests for antibody detection, and then RT-PCR tests on the positive subjects. METHODS: a simulation study is conducted to investigate the number of RT-PCR tests required by the screening strategy and the undetected ongoing infections in a pseudo-population of 500,000 subjects, under different prevalence scenarios and assuming a sensitivity of the serological test ranging from 0.50 to 0.80 (specificity 0.98). A compartmental model is used to predict the number of new infections generated by the false negatives two months after the screening, under different values of the infection reproduction number. RESULTS: assuming a sensitivity equal to 0.80 and a prevalence of 0.3%, the screening procedure would require on average 11,167 RT-PCR tests and would produce 300 false negatives, responsible after two months of a number of contagions ranging from 526 to 1,132, under the optimistic scenario of a reproduction number between 0.5 to 1. Resources and false negatives increase with the prevalence. CONCLUSIONS: the analysed screening procedure should be avoided unless the prevalence and the rate of contagion are very low. The cost and effectiveness of the screening strategies should be evaluated in the actual context of the epidemic, accounting for the fact that it may change over time.

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial.

BACKGROUND: Low syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China. METHODS AND FINDINGS: An open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing. CONCLUSIONS: Compared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested). TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900022409.

Pooled testing efficiency increases with test frequency.

Pooled testing increases efficiency by grouping individual samples and testing the combined sample, such that many individuals can be cleared with one negative test. This short paper demonstrates that pooled testing is particularly advantageous in the setting of pandemics, given repeated testing, rapid spread, and uncertain risk. Repeated testing mechanically lowers the infection probability at the time of the next test by removing positives from the population. This effect alone means that increasing frequency by x times only increases expected tests by around [Formula: see text] However, this calculation omits a further benefit of frequent testing: Removing infections from the population lowers intragroup transmission, which lowers infection probability and generates further efficiency. For this reason, increasing testing frequency can paradoxically reduce total testing cost. Our calculations are based on the assumption that infection rates are known, but predicting these rates is challenging in a fast-moving pandemic. However, given that frequent testing naturally suppresses the mean and variance of infection rates, we show that our results are very robust to uncertainty and misprediction. Finally, we note that efficiency further increases given natural sampling pools (e.g., workplaces, classrooms) that induce correlated risk via local transmission. We conclude that frequent pooled testing using natural groupings is a cost-effective way to provide consistent testing of a population to suppress infection risk in a pandemic.

Routine, Cost-Effective SARS-CoV-2 Surveillance Testing Using Pooled Saliva Limits Viral Spread on a Residential College Campus.

Routine testing for SARS-CoV-2 is rare for institutes of higher education due to prohibitive costs and supply chain delays. During spring 2021, we routinely tested all residential students 1 to 2 times per week using pooled, RNA-extraction-free, reverse transcription quantitative PCR (RT-qPCR) testing of saliva at a cost of $0.43/sample with same-day results. The limit of detection was 500 copies/ml on individual samples, and analysis indicates 1,000 and 2,500 copies/ml in pools of 5 and 10, respectively, which is orders of magnitude more sensitive than rapid antigen tests. Importantly, saliva testing flagged 83% of semester positives (43,884 tests administered) and was 95.6% concordant with nasopharyngeal diagnostic results (69.0% concordant on the first test when the nucleocapsid gene (N1) cycle threshold (CT) value was >30). Moreover, testing reduced weekly cases by 59.9% in the spring despite far looser restrictions, allowing for more normalcy while eliminating outbreaks. We also coupled our testing with a survey to clarify symptoms and transmissibility among college-age students. While only 8.5% remained asymptomatic throughout, symptoms were disparate and often cold-like (e.g., only 37.3% developed a fever), highlighting the difficulty with relying on symptom monitoring among this demographic. Based on reported symptom progression, we estimate that we removed 348 days of infectious individuals by routine testing. Interestingly, viral load (CT value) at the time of testing did not affect transmissibility (R2 = 0.0085), though those experiencing noticeable symptoms at the time of testing were more likely to spread the virus to close contacts (31.6% versus 14.3%). Together, our findings support routine testing for reducing the spread of SARS-CoV-2. Implementation of cost- and resource-efficient approaches should receive strong consideration in communities that lack herd immunity. IMPORTANCE This study highlights the utility of routine testing for SARS-CoV-2 using pooled saliva while maintaining high sensitivity of detection (under 2,500 copies/ml) and rapid turnaround of high volume (up to 930 samples in 8 h by two technicians and one quantitative PCR [qPCR] machine). This pooled approach allowed us to test all residential students 1 to 2 times per week on our college campus during the spring of 2021 and flagged 83% of our semester positives. Most students were asymptomatic or presented with symptoms mirroring common colds at the time of testing, allowing for removal of infectious individuals before they otherwise would have sought testing. To our knowledge, the total per-sample consumable cost of $0.43 is the lowest to date. With many communities still lagging in vaccination rates, routine testing that is cost-efficient highlights the capacity of the laboratory's role in controlling the spread of SARS-CoV-2.

Modeling the effectiveness of olfactory testing to limit SARS-CoV-2 transmission.

A central problem in the COVID-19 pandemic is that there is not enough testing to prevent infectious spread of SARS-CoV-2, causing surges and lockdowns with human and economic toll. Molecular tests that detect viral RNAs or antigens will be unable to rise to this challenge unless testing capacity increases by at least an order of magnitude while decreasing turnaround times. Here, we evaluate an alternative strategy based on the monitoring of olfactory dysfunction, a symptom identified in 76-83% of SARS-CoV-2 infections-including those with no other symptoms-when a standardized olfaction test is used. We model how screening for olfactory dysfunction, with reflexive molecular tests, could be beneficial in reducing community spread of SARS-CoV-2 by varying testing frequency and the prevalence, duration, and onset time of olfactory dysfunction. We find that monitoring olfactory dysfunction could reduce spread via regular screening, and could reduce risk when used at point-of-entry for single-day events. In light of these estimated impacts, and because olfactory tests can be mass produced at low cost and self-administered, we suggest that screening for olfactory dysfunction could be a high impact and cost-effective method for broad COVID-19 screening and surveillance.

College Campuses and COVID-19 Mitigation: Clinical and Economic Value.

BACKGROUND: Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses. DESIGN: The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions. DATA SOURCES: Data from published literature were used to obtain parameters related to COVID-19 and contact-hours. TARGET POPULATION: Undergraduate students and faculty at U.S. colleges. TIME HORIZON: One semester (105 days). PERSPECTIVE: Modified societal. INTERVENTION: COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening. OUTCOME MEASURES: Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY). RESULTS OF BASE-CASE ANALYSIS: Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600). RESULTS OF SENSITIVITY ANALYSIS: Results were most sensitive to test costs. LIMITATION: Data are from multiple sources. CONCLUSION: Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive. PRIMARY FUNDING SOURCE: National Institutes of Health.

A Nonadaptive Combinatorial Group Testing Strategy to Facilitate Health Care Worker Screening during the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Outbreak.

Routine testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in health care workers (HCWs) is critical. Group testing strategies to increase capacity facilitate mass population testing but do not prioritize turnaround time, an important consideration for HCW screening. We propose a nonadaptive combinatorial (NAC) group testing strategy to increase throughput while facilitating rapid turnaround. NAC matrices were constructed for sample sizes of 700, 350, and 250. Matrix performance was tested by simulation under different SARS-CoV-2 prevalence scenarios of 0.1% to 10%. NAC matrices were compared versus Dorfman sequential (DS) group testing approaches. NAC matrices performed well at low prevalence levels, with an average of 97% of samples resolved after a single round of testing via the n = 700 matrix at a prevalence of 1%. In simulations of low to medium (0.1% to 3%) prevalence, all NAC matrices were superior to the DS strategy, measured by fewer repeated tests required. At very high prevalence levels (10%), the DS matrix was marginally superior, although both group testing approaches performed poorly at high prevalence levels. This strategy maximizes the proportion of samples resolved after a single round of testing, allowing prompt return of results to HCWs. This methodology may allow laboratories to adapt their testing scheme based on required throughput and the current population prevalence, facilitating a data-driven testing strategy.

Identifying optimal COVID-19 testing strategies for schools and businesses: Balancing testing frequency, individual test technology, and cost.

BACKGROUND: COVID-19 test sensitivity and specificity have been widely examined and discussed, yet optimal use of these tests will depend on the goals of testing, the population or setting, and the anticipated underlying disease prevalence. We model various combinations of key variables to identify and compare a range of effective and practical surveillance strategies for schools and businesses. METHODS: We coupled a simulated data set incorporating actual community prevalence and test performance characteristics to a susceptible, infectious, removed (SIR) compartmental model, modeling the impact of base and tunable variables including test sensitivity, testing frequency, results lag, sample pooling, disease prevalence, externally-acquired infections, symptom checking, and test cost on outcomes including case reduction and false positives. FINDINGS: Increasing testing frequency was associated with a non-linear positive effect on cases averted over 100 days. While precise reductions in cumulative number of infections depended on community disease prevalence, testing every 3 days versus every 14 days (even with a lower sensitivity test) reduces the disease burden substantially. Pooling provided cost savings and made a high-frequency approach practical; one high-performing strategy, testing every 3 days, yielded per person per day costs as low as $1.32. INTERPRETATION: A range of practically viable testing strategies emerged for schools and businesses. Key characteristics of these strategies include high frequency testing with a moderate or high sensitivity test and minimal results delay. Sample pooling allowed for operational efficiency and cost savings with minimal loss of model performance.

Clinical and Economic Effects of Widespread Rapid Testing to Decrease SARS-CoV-2 Transmission.

BACKGROUND: The value of frequent, rapid testing to reduce community transmission of SARS-CoV-2 is poorly understood. OBJECTIVE: To define performance standards and predict the clinical, epidemiologic, and economic outcomes of nationwide, home-based antigen testing. DESIGN: A simple compartmental epidemic model that estimated viral transmission, portrayed disease progression, and forecast resource use, with and without testing. DATA SOURCES: Parameter values and ranges as informed by Centers for Disease Control and Prevention guidance and published literature. TARGET POPULATION: U.S. population. TIME HORIZON: 60 days. PERSPECTIVE: Societal; costs included testing, inpatient care, and lost workdays. INTERVENTION: Home-based SARS-CoV-2 antigen testing. OUTCOME MEASURES: Cumulative infections and deaths, number of persons isolated and hospitalized, and total costs. RESULTS OF BASE-CASE ANALYSIS: Without a testing intervention, the model anticipates 11.6 million infections, 119 000 deaths, and $10.1 billion in costs ($6.5 billion in inpatient care and $3.5 billion in lost productivity) over a 60-day horizon. Weekly availability of testing would avert 2.8 million infections and 15 700 deaths, increasing costs by $22.3 billion. Lower inpatient outlays ($5.9 billion) would partially offset additional testing expenditures ($12.5 billion) and workdays lost ($14.0 billion), yielding incremental cost-effectiveness ratios of $7890 per infection averted and $1 430 000 per death averted. RESULTS OF SENSITIVITY ANALYSIS: Outcome estimates vary widely under different behavioral assumptions and testing frequencies. However, key findings persist across all scenarios, with large reductions in infections, mortality, and hospitalizations. Costs per death averted are roughly an order of magnitude lower than commonly accepted willingness-to-pay values per statistical life saved ($5 to $17 million). LIMITATIONS: Analysis was restricted to at-home testing. There are uncertainties concerning test performance. CONCLUSION: High-frequency home testing for SARS-CoV-2 with an inexpensive, imperfect test could contribute to pandemic control at justifiable cost and warrants consideration as part of a national containment strategy. PRIMARY FUNDING SOURCE: National Institutes of Health.

Evaluation of sample pooling for screening of SARS CoV-2.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. OBJECTIVES: To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. METHODS: We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200µL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. RESULTS: We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. CONCLUSIONS: The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don't advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large.

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost-benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.

Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for Adults Experiencing Sheltered Homelessness During the COVID-19 Pandemic.

Importance: Approximately 356 000 people stay in homeless shelters nightly in the United States. They have high risk of contracting coronavirus disease 2019 (COVID-19). Objective: To assess the estimated clinical outcomes, costs, and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness. Design, Setting, and Participants: This decision analytic model used a simulated cohort of 2258 adults residing in homeless shelters in Boston, Massachusetts. Cohort characteristics and costs were adapted from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were taken from published literature and national databases. Surging, growing, and slowing epidemics (effective reproduction numbers [Re], 2.6, 1.3, and 0.9, respectively) were examined. Costs were from a health care sector perspective, and the time horizon was 4 months, from April to August 2020. Exposures: Daily symptom screening with polymerase chain reaction (PCR) testing of individuals with positive symptom screening results, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternative care sites (ACSs) for mild or moderate COVID-19, and temporary housing were each compared with no intervention. Main Outcomes and Measures: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case of COVID-19 prevented. Results: The simulated population of 2258 sheltered homeless adults had a mean (SD) age of 42.6 (9.04) years. Compared with no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild or moderate disease was associated with 37% fewer infections (1954 vs 1239) and 46% lower costs ($6.10 million vs $3.27 million) at an Re of 2.6, 75% fewer infections (538 vs 137) and 72% lower costs ($1.46 million vs $0.41 million) at an Re of 1.3, and 51% fewer infections (174 vs 85) and 51% lower costs ($0.54 million vs $0.26 million) at an Re of 0.9. Adding PCR testing every 2 weeks was associated with a further decrease in infections; incremental cost per case prevented was $1000 at an Re of 2.6, $27 000 at an Re of 1.3, and $71 000 at an Re of 0.9. Temporary housing with PCR every 2 weeks was most effective but substantially more expensive than other options. Compared with no intervention, temporary housing with PCR every 2 weeks was associated with 81% fewer infections (376) and 542% higher costs ($39.12 million) at an Re of 2.6, 82% fewer infections (95) and 2568% higher costs ($38.97 million) at an Re of 1.3, and 59% fewer infections (71) and 7114% higher costs ($38.94 million) at an Re of 0.9. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission. Conclusions and Relevance: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in SARS-CoV-2 infections at modest incremental cost and should be considered during future surges.

Pay to skip the line: The political economy of digital testing services for HIV and other sexually transmitted infections.

The value of digital healthcare has been lauded in Canada at local, provincial, and national levels. Digital medicine is purported to enhance patient access to care while promising cost savings. Using institutional ethnography, we examined the potential for publicly funded digital testing for HIV and other sexually transmitted infections (STI) in Ontario, Canada. Our analyses draw from 23 stakeholder interviews with healthcare professionals conducted between 2019 and 2020, and textual analyses of government documents and private, for-profit digital healthcare websites. We uncovered a "two-tiered" system whereby private digital STI testing services enable people with economic resources to "pay to skip the line" queuing at public clinics and proceed directly to provide samples for diagnostics at local private medical labs. In Ontario, private lab corporations compete for fee-for-service contracts with government, which in turn organises opportunities for market growth when more patient samples are collected vis-à-vis digital testing. However, we also found that some infectious disease specimens (e.g., HIV) are re-routed for analysis at government public health laboratories, who may be unable to manage the increase in testing volume associated with digital STI testing due to state budget constraints. Our findings on public-private laboratory funding disparities thus discredit the claims that digital healthcare necessarily generates cost savings, or that it enhances patients' access to care. We conclude that divergent state funding relations together with the creeping privatisation of healthcare within this "universal" system coordinate the conditions through which private corporations capitalise from digital STI testing, compounding patient access inequities. We also stress that our findings bring forth large scale implications given the context of the global COVID-19 pandemic, the rapid diffusion of digital healthcare, together with significant novel coronavirus testing activities initiated by private industry.