ASSURED-SQVM diagnostics for COVID-19: addressing the why, when, where, who, what and how of testing

Abstract

Introduction: SARS-CoV-2, the new coronavirus that originated in 2019, continues to impact every aspect of society in a profound manner. Testing will remain an important tool to mitigate the effects of this pandemic as early and accurate diagnosis can lead to appropriate countermeasures to reduce mortality and morbidity. However, testing isn't a simple yes/no answer as the target and host are complex, the virus is a moving target, there is a plethora of tests that identify different parts of the virus and have their own limits and range of detection, and when prevalence is low, false positives and negatives can be very high.Areas covered: This article covers all the major questions related to COVID-19 diagnostics, the why, when, where, who, what and how of testing, the different types of tests, interpretation of results and the ideal ASSURED-SQVM diagnostic. A comprehensive literature review using all the publicly available databases and government websites and reports was performed.Expert opinion: Diagnostics that meet the 'ASSURED-SQVM' (Affordable, Selective and Sensitive, User-friendly, Rapid and Robust, Equipment-free, Deliverable to end-users and additionally, allows for Self-testing, Quantifiable, detects if pathogens are Viable and can detect Multiple pathogens) would make a major impact in our fight against the current pandemic. While a significant majority of researchers focus on developing novel diagnostics that are highly selective and sensitive, it is the opinion of these authors that other aspects of the ASSURED-SQVM principles also be considered early in the development process for widespread use.

Keywords: ASSURED-SQVM; Covid-19; PCR; SARS-CoV-2; diagnostics; influenza; pandemic; rapid diagnostics.

Figure 1.

Timeline and concentration of analytes for diagnostic assays after onset of SARS-CoV-2 infection at day zero

Figure 2.

Schematic of some of the tests used to detect SARS-CoV-2. Please note that plaque assays are meant ONLY for research purposes in specialized biosafety laboratories and not for POC diagnostics

Figure 3.

(a) Some of the terms and their derivations used in clinical diagnostics. (b) Situation 1: If 200 tests with excellent clinical selectivity and sensitivity of 99% and 50% disease prevalence are performed, only 2 individuals will be misdiagnosed as false positive or false negative. (c) Situation 2: If 2 million tests with similar parameters as in situation 1 are performed, 20,000 individuals will be misdiagnosed as false positives or false negatives. (d) Situation 3: If the disease prevalence decreases to a more realistic situation observed in the current COVID-19 pandemic, 2,000 individuals will receive a false-negative result and 18,000 individuals will receive a false-positive result. (e) Situation 4: If the test has 95% clinical selectivity and sensitivity with 10% disease prevalence, 10,000 individuals will receive a false-negative result and 90,000 individuals will receive a false-positive result. The last situation is more indicative of most diagnostics in the current COVID-19 pandemic even if a manufacturer claims 99% clinical selectivity and sensitivity, because human errors (e.g. Incorrect sample collection, variability in nasal/throat swabs, etc.) increase when tests are performed in the field

Figure 4.

Examples of decision trees based on excellent diagnostics for stakeholders. A. Clinician/Healthcare professional. B. Policymakers. C. Individual. These decision trees are not exhaustive and doesn’t take other factors specific to a particular situation into consideration