Rapid Large-Scale COVID-19 Testing during Shortages

Abstract

<jats:p>The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in economic and social lockdowns in most countries all over the globe. Early identification of infected individuals is regarded as one of the most important prerequisites for fighting the pandemic and for returning to a ‘New Normal’. Large-scale testing is therefore crucial, but is facing several challenges including shortage of sample collection tools and of molecular biological reagents, and the need for safe electronic communication of medical reports. We present the successful establishment of a holistic SARS-CoV-2 testing platform that covers proband registration, sample collection and shipment, sample testing, and report issuing. The RT-PCR-based virus detection, being central to the platform, was extensively validated: sensitivity and specificity were defined as 96.8% and 100%, respectively; intra-run and inter-run precision were &lt;3%. A novel type of sample swab and an in-house-developed RNA extraction system were shown to perform as good as commercially available products. The resulting flexibility guarantees independence from the current bottlenecks in SARS-CoV-2 testing. Based on our technology, we offered testing at local, national, and global levels. In the present study, we report the results from approx. 18,000 SARS-CoV-2 tests in almost 10,000 individuals from a low-frequency SARS-CoV-2 pandemic area in a homogenous geographical region in north-eastern Germany for a period of 10 weeks (21 March to 31 May 2020). Among the probands, five SARS-CoV-2 positive cases were identified. Comparative analysis of corresponding virus genomes revealed a diverse origin from three of the five currently recognized SARS-CoV-2 phylogenetic clades. Our study exemplifies how preventive SARS-CoV-2 testing can be set up in a rapid and flexible manner. The application of our test has enabled a safe maintenance/resume of critical local infrastructure, e.g., nursing homes where more than 5000 elderlies and caretakers got tested. The strategy outlined by the present study may serve as a blueprint for the implementation of large-scale preventive SARS-CoV-2 testing elsewhere.</jats:p>

Considerations for diagnostic COVID-19 tests

“…Therefore, a dual bottleneck emerged early on in the pandemic in terms of sourcing the biological materials as well as sourcing the primary sources for manufacturing. The shortage of reagents and disposables is one of the most obvious later-stage problems once an outbreak becomes more widespread and ultimately pandemic 80 , 81 . In such instances it may become mandatory for manufacturers to start sharing production processes and recipes for reagents 82 .…”

COVID-19 Impact on Diagnostic Innovations: Emerging Trends and Implications

“…Whilst Asia dominated the diagnostic landscape, the role of companies in Europe and North America (namely the United States) became more evident as the pandemic reached these regions and the need to increase testing capacity became more urgent [ 17 , 25 , 71 , 72 , 73 , 74 , 75 ]. As the pandemic progressed [ 76 ], the rate of diagnostic development activity gradually slowed down between May and July (Decline Deceleration Phase) ( Figure 6 ).…”

“…The focus on MDx solutions in the first wave of the pandemic is linked to the prevalence of the disease and the urgency of early detection and rapid response. Shortages of PCR consumables [ 14 , 15 , 16 , 17 , 18 ] coupled with laboratory testing capacity issues (i.e., sample processing time) [ 4 , 6 , 25 , 28 ] caused a surge in the technological advancements of a variety of molecular-based techniques including clustered regularly interspaced short palindromic repeats (CRISPR), chemiluminescent assays (CLIA) and lateral flow immunoassay (LFIA) [ 5 , 6 , 14 , 15 , 16 , 17 , 18 , 27 , 68 ]. Furthermore, the availability and distribution of these tests was accelerated by regulatory agencies issuing interim approval mechanisms to address this large-scale public health emergency [ 48 , 70 ].…”

“…Quantitative reverse transcription polymerase chain reaction (RT-qPCR) is the most widely used molecular technique for the diagnosis of SARS-CoV-2 in hospitals, laboratories and other health care facilities [ 2 , 9 , 12 , 13 ], and requires sophisticated equipment and trained laboratory staff [ 2 ]. The severity of the crisis and increasing capacity and logistical issues associated with this method (including shortages in PCR reagents [ 14 , 15 , 16 , 17 , 18 ] and the time taken to process samples [ 14 , 15 ]), led to an increase in the development and adoption of alternative diagnostic solutions (e.g., molecular [ 14 , 19 ] and immunological-based solutions [ 20 , 21 ]) to supplement PCR-based detection [ 16 , 22 , 23 , 24 , 25 ].…”

Machine learning is the key to diagnose COVID-19: a proof of concept study.

“…The gold standard for diagnosing COVID-19 is currently represented by the combination of RT-PCR and chest-CT (10). However, it is a challenge to perform these two tests on each suspected COVID-19 patient for many reasons, including reagent shortages (11), device unavailability, lack of human resources, and high costs. In addition, the time required to perform the two tests increases the risk of ED overcrowding due to numerous patients awaiting their results.…”