key: cord-0859367-x0yvryyu
authors: Morjaria, Sejal; Nouvini, Rosa; Sirintrapun, S Joseph
title: Strategic Thinking in Test Selection for Mass SARS-CoV-2 Testing
date: 2021-06-24
journal: J Appl Lab Med
DOI: 10.1093/jalm/jfab078
sha: 0e3b176a27329b9bf09d417d562518f7daaee7cb
doc_id: 859367
cord_uid: x0yvryyu

nan

Effective mass SARS-CoV-2 testing is critical to mitigating COVID-19 outbreaks and alleviating the 23 economic impact of COVID-19 lockdowns. Although vaccination will stymie severe infection and 24 potentially mitigate spread, the possibility of asymptomatic transmission, logistical issues with 25 vaccinating entire communities in a timely fashion and the questionable duration of immunity 26 jeopardize infection control. The threat of new variants escaping vaccine induced immunity and leading 27 to outbreaks also remains. For this reason, a robust testing and vaccination strategy must be 28 implemented alongside each other. Likewise, robust testing to control transmission helps maintain 29 COVID-19 elimination status once achieved either through post-infection surges or vaccination efforts. It 30 is important to not only test and quarantine individuals who display symptoms of COVID-19 but to also 31 identify individuals who are asymptomatic and pre-symptomatic. These individuals are significant 32 contributors to community SARS-CoV-2 transmission (1) and their identification can help curb outbreaks. 33 This is especially important for vulnerable communities that contain individuals of lower socioeconomic 34 status, who are often essential workers who rely on public transportation. Such communities contain a 35 higher proportion of ethnic minorities and often have higher rates of COVID-19 (2) . 36

Given the variability of COVID-19 susceptibility and prevalence amongst communities, a 37 comprehensive SARS-CoV-2 testing strategy that combines economic, logistic, and public health 38 considerations must be adopted. As a starting point, we show a thought experiment with four 39 commonly encountered scenarios on how strategic thinking in SARS-CoV-2 testing can tailor healthcare 40 policies based on community factors. 41

At the onset of the pandemic, no national testing strategy existed, leaving states and local jurisdictions 43 to develop their own. The testing landscape that emerged varied widely, with more wealthy states and 44 robust medical sectors devising comprehensive plans, while other states lagged behind. Furthermore, 45 3 some testing gaps in local communities required a federal strategy to solidify production and supply 46 chain logistics (3) which has been lagging throughout the pandemic. Even in New York, one of the richest 47 states, communities of lower socioeconomic status and minority groups, where rates of COVID-19 48 positivity and deaths were greatest, had less access to testing (4). 49

Two Imperfect Approaches to Testing 50

Public health experts, such as Mina et al. have advocated for a nationwide rapid testing program using 51 paper-based antigen tests. Such point-of-care tests (POCTs) offer accessibility and operational simplicity 52 for mass SARS-CoV-2 testing. However, POCTs are less sensitive and specific than PCR which can lead to 53 further viral spread for an FN (5). POCTs advocates show that when factoring viral load kinetic patterns, 54 high testing frequency with rapid turnaround times (TATs) and affordability to dispense on a massive 55 scale, POCTs can overcome its lower sensitivity versus PCR testing. They further conclude that POCTs 56 are most effectively used in communities where the transmissibility window is highest (6). 57

In contrast, the Great Barrington Declaration argues for communities to "perform frequent 58 polymerase chain reaction (PCR) testing" (7). Though PCR testing is the most accurate, PCR testing lacks 59 the accessibility and operational simplicity of POCTs. It also is susceptible to false-positive (FP) results 60 given its high sensitivity. FPs also pose individual risks and can undermine confidence in clinical and 61 public health efforts. As an example, FP results can delay asymptomatic patients from undergoing 62 potentially curative cancer surgery and chemotherapy. PCR also depends on strained supply chains and 63 technical expertise for processing. Such dependencies lead to slow turnaround times (TATs) for results 64 and higher testing expenses. Slow TATs can render PCR results obsolete if contagious individuals 65 continue exposing others while awaiting results. Moreover, mass PCR testing requires costly laboratory 66 equipment, expertise and testing supplies that are scarce in under-resourced communities. 67

In this paper, we do not incorporate a specimen pooling strategy for simplicity in our quest to 68 illustrate strategic thinking in the COVID-19 domain. Although specimen pooling has advantages in 69 4 conserving lab reagents and resources, reducing TATs, and lowering costs (8), it is riddled with flaws. 70

Specimen pooling is prone to FN results due to sample dilution, making it applicable only in low COVID-71 19 prevalence communities. Moreover, this testing strategy is mostly unregulated, requiring laboratory 72 expertise, not often accessible in under-resourced communities. Lastly, guidelines are absent on the 73 optimal number of individual samples pooled before FN results arise (8). 74

Our strategic framework for SARS-CoV-2 test selection accounts for three factors: 1) whether a 76 community is a "cold spot" (low COVID-19 prevalence) or "hot spot" (high COVID-19 prevalence), 2) 77 whether a community has a limited testing capacity, and 3) whether the specific scenario warrants the 78 aforementioned desirable testing features (accessibility, fast TATs, high test accuracy). By evaluating 79 these factors and making a public health risk assessment, we provide an optimal testing strategy with 80 testing logistics and performance along with policy recommendations. 81 Important measurements of test performance include sensitivity, specificity, positive predictive 82 value (PPV) and negative predictive value (NPV). PPV and NPV are meaningful in a clinical setting, but 83 these values depend on the COVID-19 prevalence. Take a cold spot community, for example, which can 84 either be one not affected by COVID-19, post-surge, or with a high level of population immunity via 85 vaccination or natural infection. The NPV for such a community is higher given the low amount of 86 circulating virus. In hot spot communities, on the other hand, PPV is higher given the higher amount of 87 circulating virus (9) . 88

Of import, people of color and low socioeconomic status often reside in hot spot communities 89 with limited testing capacities (4). There is an urgency to create better testing strategies for them as 90 such populations have more COVID-19 cases and suffer more morbidity and mortality. According to the 91 CDC, when compared to non-Hispanic White persons, Black, Hispanic and American Indian/Alaska Native 92 persons are 2.8, 2.8 and 2.6 times more likely to die from COVID-19, respectively (10). Part of these 93 5 disproportionate effects arises from existing healthcare and structural disparities that have led to a 94 higher prevalence of severe COVID-19 risk comorbidities such as respiratory illnesses and hypertension 95 (C11). Furthermore, structural disparities such as living in multigenerational homes and employment as 96 essential workers makes social distancing and quarantine/isolation much more difficult thereby 97 increasing the risk of contracting COVID-19. Despite these known risks, these communities often have 98 less access to testing than their wealthier neighboring communities as was seen in New York City during 99 the surge (4). This argues for increasing the availability of POCTs given their higher accuracy in such 100 higher prevalence settings as well as their lower cost and resource utilization. 101

Taking all of this into consideration, we introduce thought experiments for four frequently encountered 103 community scenarios (Figure 1) . 104 Overall, our testing strategy will increase the accessibility and therefore the frequency of 150 testing. This in turn will allow for transmission control, infection rate monitoring and mitigating the 151 impact of COVID-19 in healthcare and social care settings (Table 1) . 152 153

Mass SARS-CoV-2 testing and other proven strategies (social distancing, mask-wearing, etc.) 155 help mitigate COVID-19 and its community impacts. We address the most significant gap in the COVID-156 19 public policy conversation: a one-size-fits-all mass testing edict. By leveraging testing resources 157 strategically, our framework applies risk assessments for frequently encountered community scenarios. 158

Our thought experiments show logical reasoning, based on community variables, in selecting, 159 prioritizing, and allocating testing resources to communities affected by the COVID-19 pandemic. We 160 intend for our thought experiments to stimulate consensus among expert groups, presumably consisting 161 of physicians, health policymakers, epidemiologists, economists, and politicians. Such groups are more 162 apt to build testing strategies with logistics and policy for more complicated community scenarios, like 163 8 "back to school/college" and "return to work" situations, that optimize individual health, public health, 164 

Guidance for expanded screening testing to reduce silent 181 spread of sars-cov-2

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