A Tale of Trial and Triumph: Molecular Diagnostics for Severe Acute Respiratory Coronavirus 2 Over the First Two Years of the Coronavirus Disease 2019 Pandemic

Published:April 05, 2022DOI:
      Without doubt, the coronavirus disease 2019 (COVID-19) pandemic has been the most serious health crisis to impact the world since the 1918 influenza pandemic. At the time of this writing, there are nearly 432 million documented cases, 5.9 million deaths, and an untold number of people suffering from chronic symptoms.
      Johns Hopkins Coronavirus Resource Center. 2020. COVID-19 Map – Johns Hopkins Coronavirus Resource Center.
      COVID-19 is caused by an infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded, positive-sense, enveloped RNA virus of the sarbecovirus subgenus that is transmitted primarily through respiratory droplets.
      Diagnosis of SARS-CoV-2 infection is one of the 4 pillars of COVID-19 pandemic control, alongside nonpharmacologic interventions, vaccination, and genomic surveillance. Despite years of experience with molecular diagnostics for respiratory viruses, laboratories across the world faced an unprecedented challenge in having to rapidly build, scale, and diversify SARS-CoV-2 testing capacity. Some of these challenges were due to the virus itself, including its penchant for transmission from asymptomatic carriers and its ability to evolve under immune selective pressure. However, other equally challenging problems were due to crippling supply chain issues, and a regulatory infrastructure ill equipped to handle a fast-moving emergency.
      In this issue of Clinics in Laboratory Medicine, we have assembled a series of articles that provide a comprehensive overview of the state of SARS-CoV-2 molecular testing two years into the COVID-19 pandemic. Our intention is to provide readers deep insight into the experiences of clinical laboratories around the world, written by leading experts with first-hand experience from the frontlines. We cover a diverse set of topics ranging from detailed looks at the major commercial molecular assays deployed in the United States (articles in this issue, “Analytic and Clinical Performance of Major Commercial SARS-CoV-2 Molecular Assays in the United States” by Campbell and Binnicker and “The Successes and Challenges of SARS-CoV-2 Molecular Testing in the United States” by Bard), Europe (“An Overview of SARS-CoV-2 Molecular Assays in Europe” by Davies and colleagues), and Asia (“SARS-CoV-2 Molecular Diagnostics in China” by Sun and Lu and online article by Heueh), to the benefits and pitfalls of testing at the point of care, in the form of either rapid antigen detection tests (“Rapid Antigen Assays for SARS-CoV-2: Promise and Peril” by Truong and colleagues) or molecular assays (“Point-of-Care Molecular Assays for SARS-CoV-2” by Tolan and Horowitz). We discuss the use of cycle threshold values for clinical decision making, as this is a completely novel use of respiratory viral diagnostics that has now become routine practice at many institutions (“Cycle Threshold Values from SARS-CoV-2 PCR Assays: Interpretation and Potential Use Cases” by McAdam). In addition, a key aspect of pandemic control is the ability to conduct mass testing; thus, we present a pair of articles that discuss the performance of alternative specimen types (“Performance of Nonnasopharyngeal Sample Types for Molecular Detection SARS-CoV-2” by Kukull and colleagues) and strategies used by labs to scale up their capacity (“Strategies for Scaling Up SARS-CoV-2 Molecular Testing Capacity” by Das and Frank). As disparities in access to SARS-CoV-2 testing have been a serious issue throughout the pandemic, we include a review of the many challenges with validating and scaling up testing in underresourced regions of the world (“Approaches to Deployment of Molecular Testing for SARS-CoV-2 in Resource-Limited Settings” by Bandawe). Finally, we present an overview of next-generation diagnostics that seek to overcome the problems of our existing technologies (“Novel Assays for Molecular Detection of SARS-CoV-2” by Pettengill and colleagues), an area of intense research and a silver lining hidden in this crisis.
      SARS-CoV-2 is the third coronavirus to enter circulation in human populations in the past 20 years. With climate change, increasing encroachment into animal reservoirs, and world travel, it is nearly certain that we will experience another global pandemic in our lifetime. Thus, it is incumbent upon us to learn from the innumerable failures and successes of SARS-CoV-2 testing over the past two years, as we will undoubtably rely on this important knowledge base the next time the world faces a global health emergency.


      1. Johns Hopkins Coronavirus Resource Center. 2020. COVID-19 Map – Johns Hopkins Coronavirus Resource Center.
        (Available at:) (Accessed February 24, 2022)