Immunological considerations for laboratory staff and COVID-19 biosafety

Highlights

• •The COVID-19 pandemic has highlighted the exposure of laboratory staff to this infectious disease.
• •As the pandemic progresses towards an endemic phase, COVID-19 should be re-considered as an occupational disease for laboratory staff.
• •Different surveillance strategies can be deployed, taking into consideration biosafety and immunological aspects.

Abstract

The vulnerability of healthcare and laboratory to potential infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has thus far been analyzed through the lens of the acute phase of the pandemic, including remote-based work, as well as emergency settings that are different from routine healthcare operations. However, as lockdowns ease and activities return to an identifiable pre-pandemic routine, the safety considerations also require to shift accordingly. As laboratory workers are likely to continue being exposed to unidentified SARS-CoV-2 positive samples through routine blood collection and processing operations, coronavirus disease 2019 (COVID-19) might have to be re-considered as an occupational disease within this context. Additionally, as per many such occupational diseases, a surveillance system is implemented for the medium- and long-term. This manuscript presents the views on the possible surveillance scenarios for laboratory staff, viewed from an immunological and biosafety perspective.

1. Introduction

The ongoing coronavirus disease 2019 (COVID-19) pandemic has exerted significant pressure on healthcare systems, resulting in an unprecedented global crisis, with millions of lives lost, public health systems in shock, and economic and social disruption. Within three years, COVID-19 challenged local, national, regional, and global capacities to prepare and respond to the immediate needs and recurrent epidemiological waves [1], [2], as well as to plan for the transformation of the healthcare systems in the medium-and long-term [3], [4]. At the same time, the pandemic has acted as a catalyst for the development of innovative microbiological capabilities based on accuracy, flexibility of use, and reporting speed. Characteristic examples are the creation of many different diagnostics methodologies [5], and the evaluation and increase in laboratory capacities [6].

In the post-pandemic phase, it is anticipated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, could develop into an endemic seasonal coronavirus infection, similar to the transition of the 2009 A/H1N1 pandemic influenza into a seasonal influenza virus [7]. This would likely mean the introduction of surveillance mechanisms (nationally and internationally) for the early detection of potential outbreaks at the population level, as well as the introduction of many of the created diagnostic platforms into routine healthcare practice in microbiological laboratories, additional to existing requirements. However, this likely scenario raises biosafety questions relating to the immunological status of healthcare workers (HCWs) in particular of laboratory workers who are likely to be exposed to a highly transmissible pathogen such as SARS-CoV-2, albeit a low-risk one as current vaccines afford adequate immunological protection [8].

Using COVID-19 as an example, this manuscript highlights the immunological considerations for workers in biosafety-level laboratories both within routine healthcare and healthcare research environments. In doing so, the concepts of herd immunity of defined professional population groups are taken into consideration, as well as any potential differences/recommendations to the current biosafety considerations within laboratories. Thus, the aspects presented here, are relate to the immunological considerations for staff in general, both for scientific research and routine healthcare provision, and the associated biological safety aspects.

2. Re-evaluating COVID-19 biosafety as an occupational disease

Healthcare and laboratory workers are known to be at risk of occupational exposure to blood and other infectious bodily fluids [9]. For example, it has been shown that in sub-Saharan Africa almost one-half of the healthcare personnel (including frontline staff and laboratory workers) were occupationally exposed to body fluids annually [10]. This has been no different in the case of COVID-19, where frontline staff was at a higher risk of infection. Laboratory staff was also reported as infected albeit at lower numbers [11], [12]. According to the current international definition, if healthcare personnel are infected while performing their tasks, the condition is then defined as an occupational disease [13]. Laboratory-acquired infections represent an occupational disease unique to laboratory workers, especially in clinical microbiology settings. A risk assessment for infection is an important tool in minimizing potential infections by COVID-19 and other infectious agents. The risk assessment should be based on a number of parameters, such as the host's immune system, mechanism of the exposure, the infectious dose of the exposure, the virulence of the agent, the use of personal protective equipment, and immunization status, though the accurate quantification of such a risk can often be challenging in practice [14], [15]. However, risk assessments are indeed effective even if not all of the previously mentioned parameters are available all of the time.

Under the weight of current evidence, and the likely persistence of COVID-19 in the general population, it is appropriate that COVID-19 is viewed through the lens of an occupational disease for laboratory staff. To this end, the relative risk of infection would need to be established, as not every exposure would result in a potential infection, so that occupational exposure limits would be estimated. Conceptually, exposure is calculated according to the E = C × Δt formulation, where C is the concentration of the agent and Δt the duration of exposure. However, defining the parameters influencing the variables of this formula necessitates that the routes of exposure to the virus should be known well – which is not currently the case with COVID-19 [16], as the latter has not been studied extensively within the occupational environment of laboratories for all SARS-CoV-2 variants. Having said that, according to the interim analysis by the United States Occupational Safety and Health Administration (OSHA) laboratory staff, who do not come into contact with patients during their work, would fall under the low-risk category [17]. In the calculation of the latter risk, it was taken into account that laboratory staff would be fully adherent to protective measures at all times, which has not been the case in many settings, as the sharp rise in positive cases and the pressures on local healthcare systems meant that sometimes protective measures, such as personal and collective protective equipment, were not always available in the quantities needed. Thus, it becomes of interest to contemplate if surveillance should be advocated for laboratory staff, and if yes, which models would be considered.

3. Potential surveillance options for laboratory staff

Surveillance of occupational diseases can fall into two broad categories: passive or active. Passive surveillance often relies on the self-monitoring of staff and/or the reporting of infections by local physicians/institutions to relevant authorities. In many countries, such surveillance is legally mandated, aligned with the International Labour Organization convention C155, stating that all countries should maintain a registration system that is capable of providing information to policymakers [18]. However, the exact surveillance mechanism is country-dependent, thus a large diversity of systems exists (e.g., national registries), complemented by additional schemes linked to national financial compensation systems and/or social security systems. Furthermore, definitions, diagnostic guidelines, notification criteria and the local legal context differ significantly [19]. As such, while passive surveillance might derive from a common need caused by the pandemic, the implementation is likely to be equally as fragmented as with other occupational disease surveillance.

On the other hand, active surveillance requires regular, purposive sampling across a pre-defined target population(s). As such, the implemented protocols would need to be well-defined starting by the definition of COVID-19 cases so that such a program may assume a perfect ascertainment of symptomatic cases that develop under active monitoring. Alternatively, immunological surveillance might be easier to achieve, following blueprints that have been set for healthcare workers in general [20]. However, given the many challenges that active surveillance implementation faced across the world so far, doing so for the long-term is likely to amplify those challenges, even if it targets a smaller population [21]. Therefore, it is likely that surveillance of COVID-19 for laboratory staff would follow precedents set for other respiratory viral pathogens, such as influenza, where a passive surveillance system would occur aligned with existing systems, and complemented where and when necessary, by an active preventative campaign, such as vaccination. In particular the latter, can be based on the well-characterised cycles of immunological responses to vaccination at a population level [22], which may eventually become easier to correlate with a potential settling of SARS-CoV-2 infections into a better predictable seasonal cycle [23].

Active surveillance can incorporate a number of actionable constituent parts so that they are best adapted to local needs and pressures. Specifically, these can be vaccination, post-vaccination surveillance, post-infection recommendations, as well as the adaptation of working arrangements – all the above are connected through an eHealth infrastructure so that the nature of the surveillance can be as dynamic and responsive as possible. In the case of influenza, the predictable seasonality of the infections allows vaccination campaigns for healthcare staff to be planned ahead of the anticipated peak of infections. In some cases, the mandatory nature of such vaccination campaigns for HCWs has also been considered [24]. A similar approach may be envisaged for COVID-19, with targeted vaccination campaigns on an iterative basis, and with an aim of 75% coverage as per the Influenza recommendations. The local adaptation and implementation can use the existing guidance by the WHO ‘Tailoring Immunization Programmes for Seasonal Influenza’ as the blueprint [25]. Complementary to the vaccination campaigns, the implementation of personal protective equipment can follow the existing WHO Disease Commodity Package (DCP) for COVID-19, a datasheet that lists critical commodities and technical specifications [26].

Regarding COVID-19 post-vaccination surveillance, a number of serological-based protocols have been successfully applied to laboratory staff [12], [27]. While there is not yet an emerging consensus on a protocol for post-vaccination surveillance, there have been operative protocols for the vaccination prophylaxis of healthcare workers (including laboratory staff) implemented in recent years [28], and typically the serological test is performed 1 month following vaccination [29]. The WHO International Standard for evaluation of the antibody response to COVID-19 vaccines was recently established [30]. The challenge for 2023 remains to ensure the use of this antibody standard in vaccine clinical trials, assisting in the interpretation of results (by providing the basis for the expression of antibody titres in international units (IU) and allowing comparability of studies), as well as in establishing correlates of protection [31].

Lastly, despite all the above protective measures, laboratory staff remain likely to become infected albeit at a low risk. Therefore, occupational health departments are expected to take a leading role in managing the healthcare workforce. Post-infection recommendations by the USA CDC currently state that COVID-19-positive staff members need to meet all of the following criteria: 1) At least 7 days have passed since symptoms first appeared if a negative viral test (molecular or antigen) is obtained within 48 h prior to returning to work (or 10 days if testing is not performed or if a positive test at day 5–7); 2) at least 24 h have passed since last fever without the use of fever-reducing medications; and 3) symptoms (e.g., cough, shortness of breath) have improved [32]. These are likely to remain in the near future. Thus, managerial measures may need to be taken to allow for greater adaptability at work, such as: restricting workplace access to workers with specific training and skills for protection; ensuring appropriate working hours; rostering and, where possible, avoiding workers being shifted from high to low transmission settings. Additional measures may include the addition of surge personnel to meet work demands; ‘closed-network’ employee carpooling for commuting to work, and others. Interim guidance on health workforce policy has been published by the WHO, though these are high-level recommendations that require further context-driven nuancing [33].

4. Conclusion

As SARS-CoV-2 infections are likely to continue to occur in the community in the short- and medium-term, the quick detection of cases through laboratories would be a critical component in containing future epidemic outbreaks. Additionally, it is likely that increasing numbers of undetected SARS-CoV-2 positive blood samples will be analyzed by laboratory staff as part of routine healthcare services and research activities. Thus, due to the increased exposure of laboratory staff to potentially infected fluids, COVID-19 might have to be reconsidered as an occupational disease. Given the relatively low biosafety level attributed in the latter case by the CDC in the USA and other relevant institutions, a number of immunological requirements for workers in laboratories would need to be considered.

As the natural (through infection) or induced (through vaccination) immunological response to SARS-CoV-2 infection wanes over time, a blanket once-off approach would not be possible to achieve regarding inducing long-term protection for laboratory workers. Furthermore, because of the nature of the immunological response, the concept of herd immunity is also a very difficult aim to achieve and maintain. Therefore, maintaining a surveillance system would be a more likely scenario. In this case, prior experience with another seasonal respiratory pathogen, influenza, points towards a passive surveillance system, complemented seasonally with active campaigns of vaccination to raise the protection levels of potentially exposed staff. It is thus evident, that the joint consideration of immunology and biosafety are the key components in creating an evidence-based long-term policy.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/WHO.

Author contributions

Ambroise Kouame Kintossou: Formal analysis, Writing - original draft. Stephanie Villar: Writing - review & editing, Writing - original draft. Zisis Kozlakidis: Conceptualization, Methodology, Supervision, Writing - review & editing.