Practical problems and responses for SARS-CoV-2 laboratory testing during the COVID-19 pandemic

Although laboratory issues were considered part of pandemic preparedness in many countries, it was difficult to anticipate the unexpected challenges and unprecedented demands in delivering SARS-CoV-2 testing during the COVID-19 pandemic. As the pandemic evolved, particularly during the first 2 years, significant pressures were placed on laboratories worldwide to provide timely SARS-CoV-2 testing, in addition to the routine tests required for other illnesses.

Rapidly changing government and central laboratory mandates, obscure tendering processes [1,2], requirements for rapid reporting of results to guide individual patient management (in both hospital and community settings), infection control mandates placed additional stress on diagnostic laboratories. The demands for testing targets were not based on strong scientific evidence as the pandemic evolved but more on the numbers of daily cases reported by national surveillance systems and hospital admissions. Early during the pandemic, many questions were asked about the diagnostic performance of SARS-CoV-2 tests.

Evolving, real-time data on asymptomatic and pre-symptomatic SARS-CoV-2 infection and re-infection as well as viral kinetics and shedding of replication-competent viruses made regular communication with clinicians, public health physicians, policymakers, the general public and the media necessary. However, these were often limited by time pressures on laboratory scientists and microbiologists. Shortages due to supply chain issues of reagents, consumables, personal protective equipment, and staff placed additional significant strain on laboratories.

Here, we summarize our shared experiences and suggest solutions to some of the problems which we encountered during the COVID-19 pandemic, with the aim of informing and improving future pandemic preparedness of diagnostic laboratories. This is not intended to be an exhaustive review; however, in presenting our individual laboratory experiences, we hope to demonstrate to stakeholders the key role of diagnostic laboratories in the face of any new pandemic.

Rapidly changing goverment mandates

This was a common theme to varying degrees across our laboratories. Policymakers and government officials, who were unfamiliar with how diagnostic testing worked in public and private sectors, were demanding accurate results of the nucleic acid amplification test (NAAT), with rapid but often unrealistic turnaround times to screen people with suspected SARS-CoV-2 infection.

Initially, diagnostic testing was centralized in many countries, which was understandable as new NAAT assays were developed and optimized. Following this, the timely roll-out to other hospitals (where patients with suspected or confirmed COVID-19 were managed) or non-hospital-based laboratories (serving community-based patients, prisons, elderly care homes, or the general public) was delayed, until central laboratories were overwhelmed.

Although urgent and rapid reporting of results is important during the early stages of any evolving pandemic, expert virology oversight is required to assist with the interpretation of test results and enable appropriate patient management by clinical, infection control and public health teams [3,4].

Practical solutions

Governments should appoint laboratory-trained advisors with relevant diagnostic expertise to engage local diagnostic networks early in the process because they can help guide assay design, interpret results, co-ordinate supplies of testing reagents, work with regulators, and reduce the burden on central diagnostic laboratories.

Staffing shortages, training and burnout

After the roll-out to non-central laboratories, the impact and burden of SARS-CoV-2 testing during the pandemic on local diagnostic laboratories was immediate and severe. Many staff members themselves were absent because of COVID-19 or had to self-quarantine when they were identified as close contacts of cases. This occurred particularly during the early stages of the pandemic, when the incidence of COVID-19 was high in the community, mask wearing was not mandatory, and COVID-19 vaccines were not yet available. Staffing issues took several of the following forms:

• i)Absenteeism because of COVID-19, which led to staff fatigue (including increased repetitive strain injuries from manual sample processing and data entry) and longer working hours to cover for those absent.
• ii)Extended work hours (including night shifts in some laboratories) because of slow recruitment of additional staff, who were often recruited from other laboratory specialties, resulting in knock-on effects on those services.
• iii)Training of new staff by staff involved in SARS-CoV-2 testing. Those who had worked in other laboratories (such as research or non-human) often took longer to be trained because they were unfamiliar with workflows, information systems and quality assurance procedures in clinical diagnostic laboratories.
• iv)In some countries, the inability to use non-clinically trained staff (e.g. academic or research) who could perform SARS-CoV-2 testing but were not registered with or accredited by relevant authorities (or equivalent organizations) for human health diagnostic testing.
• v)The importance of maintaining a minimum number of staff members with expertise in developing, verifying and validating diagnostic assays, separate from those performing routine testing.

In order to alleviate some of these pressures, other diagnostic tests, including respiratory virus multiplex NAAT, were rationalized in some laboratories, which led to reduced information on the presence of other important pathogens. Testing of pooled samples during the early stages of the pandemic was helpful in improving the efficiency of testing and conserving testing reagents; however, this was not sustainable once the incidence of infection increased.

Although less skilled staff could be used to register samples and prepare them for testing on more fully automated platforms [5], they needed to be recruited and trained, adding to the burden on administrative and existing staff. In some laboratories, incentives or rewards, such as one-off staff bonuses, were given.

Practical solutions

Learning from and co-ordinating existing diagnostic laboratory networks will help inform decisions on how to manage staff burnout and shortages. Establishment of a register of ‘locum’ staff (including those working in academic institutions) across the country could provide support to local or distant (for those willing to travel) laboratories at short notice. The use of automated processes and platforms (e.g. liquid-handling robots) should be increased once such assays become available. Staff morale should be maintained with team-building activities (in which social distancing is allowed), confidence in leadership should be improved, and, where appropriate, salary bonuses should be provided.

Assay reagents, plastics and swab supply issues

Many laboratories ran out of nucleic acid extraction and amplification reagents, plastic ware (e.g. pipette tips and test tubes), swabs and sample transport media. With a high demand globally, countries became protectionist, with manufacturers refusing or legally unable to supply goods outside of their native countries to prioritize support for local diagnostic testing. It was not always possible to assess reagents sourced from alternative suppliers, and of those which were, some were not ‘fit for purpose’.

Although this might be understandable, on a larger, international scale, this becomes detrimental because undiagnosed or poor surveillance in potential hotspots of infection can lead to delayed identification and control of the spread of novel SARS-CoV-2 variants of concern, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) [6].

Unfortunately, there is no simple solution to supply issues which will benefit all laboratories. If each country utilized their local laboratory network to form a larger customer base to lobby suppliers, other laboratories elsewhere will lose out. Ideally, these supplies should be linked to need; however, during pandemics, the need is global. Suppliers will tend to prioritize laboratories with which they have long, existing and close commercial relationships.

Practical solutions

Individual laboratories may have to rely on personal relationships with existing suppliers to support them when the demand is high. Richer countries could, theoretically, outbid other countries for reagents; so, there may have to be some pre-established or rapidly established global principles which suppliers would need to follow to control this somewhat unethical practice. Jurisdictional laboratories with greater purchasing power because of economies of scale were more successful at leveraging manufacturers for supplies. Some countries urgently considered on-shore manufacturing of consumables, including the use of novel technologies such as three-dimensional-printed swabs [7]. The use of multiple testing platforms in each laboratory will help to mitigate reagent shortages. Stockpile options need to be considered.

Diagnostic testing for SARS-CoV-2 during the early phases of the COVID-19 pandemic reflected a chaotic and disorganized scramble for the development and roll-out of assays to meet urgent government and public health demands. This led to many errors, even by experienced laboratories [8], and bottlenecks in testing hampered effective community surveillance and public health control of the virus [9].

With this experience and hindsight, we highlight potential mitigation strategies for future pandemics and suggest more co-ordinated responses from relevant stakeholders and governments. Governments should consult their national public health laboratory networks (where such networks exist) and work with them to deliver optimal testing strategies for novel pathogens with pandemic potential [3]. Such laboratory networks can also utilize their collective existing industry contacts and ‘buy power’ to secure supplies of reagents, plastics and test kits. Finally, these networks can establish a register of laboratory staff who can be rapidly trained and deployed where needed to assist with any required laboratory workforce surge.

Author contributions

JWT initially conceived the idea for the article and proposed this to all authors. All authors (MD, PWB, JK, CKL, HN, LO, GA, DED, CWH, LCJ) were supportive of the idea and sent accounts of their own experiences of virology diagnostic testing during the COVID-19 pandemic. JWT summarized each account in an initial draft and returned it to all authors for checking or verification. JWT then drafted the final version, and all authors critically reviewed the manuscript before submission.

Transparency declaration

The authors declare that they have no conflicts of interest.

Editor: J. Hübschen