Considerations for diagnostic COVID-19 tests

Abstract

During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, design, development, validation, verification and implementation of diagnostic tests were actively addressed by a large number of diagnostic test manufacturers. Hundreds of molecular tests and immunoassays were rapidly developed, albeit many still await clinical validation and formal approval. In this Review, we summarize the crucial role of diagnostic tests during the first global wave of COVID-19. We explore the technical and implementation problems encountered during this early phase in the pandemic, and try to define future directions for the progressive and better use of (syndromic) diagnostics during a possible resurgence of COVID-19 in future global waves or regional outbreaks. Continuous global improvement in diagnostic test preparedness is essential for more rapid detection of patients, possibly at the point of care, and for optimized prevention and treatment, in both industrialized countries and low-resource settings.

Fig. 1. Advancing translational medicine.

A schematic overview of the key innovation drivers, technologies, institutes and partners needed for the development of new diagnostic tests, drugs and/or vaccines. The boxes on the left identify some of the important medical, scientific and industrial deliverables where an interconnected approach covering each steps from fundamental research to commercialization is needed. Translational medicine relies on the interconnection of multidisciplinary teams of life scientists able to translate basic scientific discoveries into changes in clinical practice supported by expertise from engineering, law and financial sciences. The most important facilitators are indicated in each box. The column on the right lists the innovation drivers. Current innovation drivers combine the ability to process large amounts of data and to facilitate access to biological material through easy access to a biobank. The intense collaboration between academia and industry, with detailed sharing of research goals and directions during the coronavirus disease 2019 (COVID-19) pandemic, through the identification of an optimal collaborative approach capitalizing on the strengths of both made possible the rapid development of new diagnostic tests, drugs and possible vaccines against COVID-19.

Fig. 2. Survey of weekly COVID-19 testing figures.

The graph shows the testing rate per 100,000 population for coronavirus disease 2019 (COVID-19) by week and by member states of the European Union and the European Economic Area, and the United Kingdom. Data provided by the European Centre for Disease Prevention and Control.

Fig. 3. Public health impact and laboratory medicine consequences of COVID-19.

The top panel provides an overview of the national and global dissemination of coronavirus disease 2019 (COVID-19), the declaration of a pandemic state, the implementation of lockdown measures and confinement, the achievement of viral sequencing and clinical assessment, and the concurrent development of diagnostic tools and their progressive implementation on the indicated timescale. The graph shows the number of confirmed COVID-19 cases by date of report and WHO region from 11 January to 31 August 2020 (from WHO Coronavirus Disease (COVID-19) Dashboard). The bottom panel shows the need for quality assessment during the route towards design and development of diagnostic tests, the test quality assessment stage and the stage during which test is formally quality approved and globally available for clinical and epidemiological use. Key ingredients and characteristics of the currently most used test formats are provided, and the continuous need for test refinement based on viral evolution is underscored. The bottom and top boxes are linked by the association between global waves of infection, vaccine development and the production, fine-tuning and degree of availability of large volumes of diagnostic tests needed for appropriate clinical care. EUA Emergency Use Authorization; FDA, US Food and Drug Administration; POC, point of care; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.