Impact of the COVID-19 pandemic on Molecular Diagnostics

Without question, COVID-19 is the most intensively studied infectious disease in history with >125,000 PubMed citations from January 2020 to April 2021. This contrasts with influenza, about 8,000 citations, and tuberculosis, 10,000 citations in the same time period.

The contributions of molecular diagnostics to COVID-19 assessment toward reduction of morbidity and mortality are widely recognized [1–3]. Still, the inevitable false negative rates have contributed to a substantial increase in cases as did delays in turn around time test reporting [1].

Less appreciated but perhaps even more important has been the impact of COVID-19 on Molecular Diagnostics testing and research for non COVID applications. In the initial phase of the pandemic, the lack of equipment, reagent capacity as well as insufficient lab environmental protection including personal protective equipment, slowed the deployment of COVID-19 molecular diagnostics while contributing to the stress and exhaustion of laboratory professionals faced with coping with sudden huge and urgent testing demands [4]. Adverse effects of the pandemic on mental health have been universal and similar irrespective of occupation but have been quantified in depth for specific groups such as high performance atheletes [5]. A collateral persisting consequence was delay in molecular diagnostic testing for other diseases in part because of redirection of resources and in part from reduction or suspension of other nonurgent care in hospital centers [6,7]. A less recognized adverse consequence has been on non COVID biologic research including molecular diagnostics. Non COVID research has been hampered for the past year by reallocation of equipment and personnel to COVID-19 studies, supply chain disruptions [8], and social distancing protocols, particularly in academic institutions. Amongst the sectors most severely affected has been hospital based clinical research [9].

Novel Molecular Diagnostics tests directed toward COVID-19 detection, identification of virus variants, inflammation mechanisms, immune specific effects on lungs and other organs, and currently, vaccine efficacy, have each played major roles in control of the pandemic.

Through prominent media presence over months, technical issues related to COVID-19 laboratory testing, which under other circumstances would have remained with laboratory professionals, now have become embedded in public discourse, worldwide. Awareness and importance of lab test performance, sensitivity and specificity, lab test capacity, and turn around time are topics that are becoming widely known for all laboratory tests. The role of lab tests in COVID-19 diagnosis, monitoring and susceptibility screening and the varied clinical guidance of test interpretation amongst vulnerable aged and immune compromised populations is becoming better understood. Similarly, the ethical, logistic and economic issues of Covid molecular diagnostics delivery to populations in less developed nations has become a matter of public debate and remedial action. Central to pandemic control and of greatest importance is equitable access throughout the world to COVID molecular diagnostics. As United Nations, Deputy Secretary-General Amina Mohammed eloquently said in July 2020,” No one will ever be truly safe until everyone is safe”[10]. The solution is in part, resides in providing adequate capacity including trained personnel, equipment platforms, reagents, all technically feasible and economically viable. Equally, to ensure that capacity is equitably distributed, is the population awareness provided by moral pressure exerted with timely, complete, and open disclosure of relevant demographic data [11].

COVID-19 has demonstrated both the power and current weaknesses of molecular diagnostics bioinformatics. On the positive side, the bionformatics capacity to determine by modeling, potential antigenic sites on the viruses, has led to successful vaccines and rapid detection of viral variants. However, the COVID-19 pandemic has demonstrated forcefully that lab informatics connectivity, throughout the world, has been woefully insufficient to provide clinical physicians, epidemiologists and public health professionals the molecular diagnostics vital information on infectivity in a sufficiently timely manner to guide pandemic control. Nonetheless, the early evidence such as that from Switzerland that rapid turnaround of molecular diagnostics coupled with rapid contact tracing is effective in control of infectivity, is a powerful stimulus to rectify lab informatics connectivity deficiencies [12].

The COVID-19 pandemic as the proverbial ill wind, has opened many beneficial future opportunities for molecular diagnostics. First, the investment and revenue in molecular diagnostics has generated large corporate funds for future investment in better tests and molecular diagnostics tests for novel applications. Similarly, the pandemic costs experienced by all nations are a huge stimulus to governments to provide incentives for fundamental research in molecular diagnostics science. These investments will have high impact beyond the pandemic as excess capacity can be reallocated to non infectious medical conditions. The challenge will be to maintain this momentum so that diagnostics capacity can be available for the next infectious disease crisis. Amongst the needs being addressed is RT-PCR instrumentation capable of providing molecular tests in larger volumes with decreased turn around time [13]. However, these instruments typically require highly trained personnel and stringent environmental conditions available only in large urban laboratories. To meet public health needs to detect positive cases, expedite isolation of individuals testing positive, and speed up contact tracing, a different delivery model is required, namely decentralized reliable point of care testing with results reporting during the same patient encounter [14]. Although more than 19 different tests have been approved for rapid COVID-19 testing, none yet fully meet requirements for sensitivity and specificity as well as rapid turnaround time [15–17]. COVID-19 has accelerated development of a wide variety of sensor based point of care methods including PCR for infectious disease detection [18]. These advances will facilitate decentralized molecular diagnostic testing not only for infectious disease but many other disorders.

The most common acute manifestation of COVID-19 leading to requirement for mechanical ventilation is pneumonia, but this may be of two types, an interstitial pneumonitis and/or a bacterial associated bronchopneumonia [19]. COVID-19 infection is rarely fulminant but early stages may go unrecognized particularly in elderly, debilitated patients. Better lab tests are still needed to assess presence, type, and intensity of lung inflammation where patients have suppressed symptoms and to discriminate between bacterial and nonbacterial inflammation.

While the molecular diagnostics advances have been instrumental in identifying patients and asymptomatic contacts with COVID-19, the tests have not realized their full potential because of inadequacies related to laboratory informatics connectivity and informatics analysis. Typically, 1–2 days pass before individuals present for testing, followed by 2–5 days for testing to be completed in a central laboratory and results returned. This compares with the estimate that each day delay in COVID-19 test results in presence of fully functioning contact tracing, increases cumulative disease incidence by 28% and resource utilization by 33%[1]. It is worthwhile reflecting on this deficiency, its massive costs, and potential solutions. Turnaround times for lab tests have been based on past expectations for health care in hospitals or ambulatory settings, not on population testing needs in a pandemic. Typically, Diagnostic Laboratories are connected electronically to units within hospitals and to particular ambulatory clients but rarely farther afield to public health units or regional governments. While the communications technology is feasible today, barriers to better interconnectivity range from presence of multiple, insufficiently standardized informatics systems in labs, public health units and regions, privacy protection concerns, to debates about which payor should bear connection costs. An option to develop low cost connectivity is to bypass legacy specialized systems and their attendant bureaucracies by using encrypted cell phones directly attached to point of care diagnostics devices and to public health units. Further, the COVID−19 pandemic is a prime example where a vast mountain of molecular diagnostics associated data has been collected, far too much to be analyzed and used most effectively in a timely manner by conventional means. The opportunity presents opportunities, first to revisit this data using artificial intelligence to discern useful patterns for early detection and assessment of Covid−19, and then to embed the algorithms into future public health informatics systems [20].

What are the lessons to be learned from molecular diagnostics experience with COVID−19 ?

It has been demonstrated that sensitive and specific molecular diagnostics tests for applications such as new pathogens can be fabricated within months. However, to be maximally effective the tests must be deployed in systems that facilitate analysis and dissemination of results, rapidly, to a wide range of decision makers. This implies that the information systems must be simplified and integrated; the ‘seams in the system’ must be reduced drastically. The COVID-19 experience has shown clearly what is needed: molecular diagnostics at point of care, with results reporting on the same visit, simultaneous export of anonymized results to public health agencies and governments, and artificial intelligence techniques to assist analysis and interpretation of test results. COVID-19 has shown that more sensitive and specific tests to assess inflammation, immune reactions and response to treatment are needed. Most interestingly, the laboratory and informatics components to meet these needs are now available as is the cost/benefit business case in terms of population health. What is needed is a consensus that lab diagnostic systems must be built now not only to serve individuals but also to support local and distant populations. The dividend from the COVID−19 experience will be future investment in molecular diagnostics. This investment promises to better our knowledge of infectious disease prevalence as well to yield novel molecular technology and specific tests for better diagnosis and control of various conditions extending well beyond infectious diseases.

The SARS epidemic of 2002–2003, which this author experienced first hand, taught many lessons about providing resilient laboratory diagnostics for health systems [21]. However, one lesson, that diagnostics for pandemic preparedness, just like clean water and fire protection, must be supported on a continuing basis, was lost after 17 years.

COVID-19 has demonstrated the need for rapid molecular diagnostics, adequately and equitably distributed and the need for lab informatics connectivity and data analysis capability at least an order of magnitude better than exists today. The response to COVID-19 has increased molecular diagnostics capacity; equitable access to diagnostics and better lab informatics systems are recognized. Remaining needs include the build out of better information systems, ongoing molecular diagnostics research to shorten test development times, shorten analytical test times and make molecular diagnostics tests more reliable.

However, the paramount need is to ensure that locally, nationally, and internationally, molecular diagnostics capacity and momentum for advancement is maintained. The powerful incentive which must be kept in forefront of decision makers is to escape the “Fate of Rome” a civilization which ultimately collapsed following the devastating Justinian pandemic [22].

Declaration of Interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.