Returning to the laboratory

NB: Official UK Government advice ‘Working safely during COVID-19 in labs and research facilities’  was released on 11 May and should be reviewed by people who work in or run indoor labs and research facilities and similar environments.

Resuming laboratory testing with human participants

This is a brief communication and is in response to a question (Q. 25) posted on The Physiological Society’s website (“Questions from the front line”). In part due to the commitment to produce a response to questions within 24 hours, and in part due to the difficulties associated with becoming too prescriptive, this article is little more than a checklist of some of the things that those returning to a laboratory setting for human testing after the lockdown period for COVID-19, might like to consider.  As such, this document carries no formal requirements or consequences. Depending on circumstance and usage, there may be additional considerations, not presented in this document, that should be implemented. Any “best practice” advice that is written will be quickly overtaken by new data and events. Procedures will evolve as reliable testing becomes more available, as vaccines emerge, and as we gain greater understanding of this disease and the nature and transmissibility of the virus.  It is to be expected that human use ethics committees will expect to see specific attention in research protocols to the protection of human subjects from COVID-19 infection.

This doesn’t stop something being written at this time to help provide guidance on what should be considered (and many groups are in the process of doing this), but it will need to come with a date and version stamp, and the advice amended in the light of new data (i.e. remain a “live” document). With this in mind, it would be helpful if those visiting The Physiological Society website submit any plans in this area as their institutions produce them (dated and referenced please).

General: Technical and maintenance guidance for re-starting a laboratory

• PA testing: does any electrical equipment require a PA test?
• CALIBRATION: do any items of equipment require new calibration certification?
• REAGENTS: are any chemicals or reagents used for testing or other activities, out of date?
• POWER: has the power to any equipment or system been shut down and need to be reinstated?
• REBOOT: does any equipment need to undergo an extended reboot process? This could potentially be done prior to the main workforce returning.
• TEST: are there systems and equipment that require a test procedure to ensure correct operation. Again this could be done prior to the main workforce returning.
• MAINTENANCE: is there general maintenance of equipment/plant that has not been undertaken during lockdown? Could this be performed prior to the main workforce returning? e.g. replacement of filters, servicing of compressors, air conditioning, boilers etc., on-site calibration of equipment. Are there specific risks related to lack of use? e.g. Legionnaire build up in mains hot water tanks.

General COVID-19-related advice

• Research involves a series of interactions with the environment, members of the research team, research participants, and those supporting the research (cleaners, administrators, delivery drivers ). Each of these interactions presents a risk of transmission of SARS-CoV-2, which in turn may result in the disease COVID-19. The UK government has some institutional guidance.
• Follow all the standard national government advice (stay away and isolate if unwell or if anyone in your household is unwell, maintain social distancing ).
• When laboratory use increases, consider the interaction of its users:
  • Consider alternate ways of working e.g. teleconference meeting for design/ planning/ data review/ participant screening etc.
  • Consider testing only one participant at a time, with the minimal required and properly protected research staff.
  • Spread interface/computer terminals apart to meet social distancing requirements.
  • Where possible establish one-way traffic systems within the building and laboratory.
  • Declutter shared workspaces to reduce the number of surfaces the virus can land on.
  • Wipe down workstations when leaving e.g. keyboards, chairs, handled equipment.
  • Reduce communal cutlery, drinks containers, shared food.
  • Encourage regular hand washing on entering and leaving the laboratory.
  • Identify specific loading/unloading delivery areas where social distancing can be maintained but deliveries remain safe and secure.
• Increase ventilation generally in the facility and particularly in confined spaces where possible:
  • Consider ventilation of laboratory/indoor confined spaces where there is either an air conditioning system or chamber environmental system running with the possibility of the presence of an infected person. Published guidance from the European ventilation and heating engineers.
  • Some related advice for airports.

Testing

• First and foremost, you should be guided by government guidance on socialising. This is evolving rapidly and should be monitored.
• Establish the position regarding the specific cover offered by your institutional insurance/compensation schemes for researchers and participants. In the UK, research staff are employees of their respective institutions and are therefore covered by the employer’s and employee’s statute responsibilities under Health & Safety at Work Act. One aspect is the protection of staff who may have underlying health problems or disability that may put them at increased risk. Seek your institution’s Occupational Health Department advice where there is doubt or concern.
• In general, testing should not restart until people are all able to move freely, and the government has allowed segments of the population to go back to work.
• Consider the ethics of performing research that utilises PPE, Coronavirus testing kits, or poses additional risk to participants of contracting COVID-19, against the outcome of studies. This will be an ongoing, context sensitive, dynamic risk assessment, balancing “benefit” against “cost” for each study in terms of the impact on society of the results, and resource use associated with conducting the study. Simply, does the benefit of the proposed research outweigh the associated risks of COVID-19 (infection, critical resource use) in society?
• Additional precautions and consent should be considered with regard to rescue and first aid/ resuscitation procedures. These may pose additional risks to rescuers with consequent alteration to protocols. The result of which may be reduced capability to resuscitate in the context of a problem, e.g. avoidance of airway manoeuvers during resuscitation as they are an Aerosol Generating Procedure.
• The requirements associated with testing with a risk of COVID-19 infection (e.g. single participant testing, PPE use) will add significantly to both the costs of studies and the time taken to complete them.
• Stratify the risk related to the testing you intend in terms of the tests to be undertaken, populations to be tested and those undertaking the testing e.g. i. Co-morbidities, age etc. of researchers and participants ii. Anything aerosol-generating will require greater distancing, unless the participant is wearing a sealed/filtered mask.
• Try to have preliminaries (recruitment, initial consenting, health history, questionnaires) moved online. This approach requires additional consideration to ensure participant confidentiality (e.g. privacy of internet connection, notification, privacy and storage of any conversations/data recorded).
• Consider testing for infection as part of remote screening pre and post experimentation. In repeat measures experiment (over several days) ask the participant to report daily symptoms (look out for fever, cough, changes in respiratory parameters) and follow-up on post experiment health.
• If allowed to move freely, but with an element of social distancing, then you could consider testing provided:
  • You work on the assumption of contamination (as with precautions for blood sampling).
  • The researchers, participant and both their households are asymptomatic.
  • You can maintain appropriate distances (e.g. participants could be instructed to wire themselves up).
• Minimise the number of individuals using specific pieces of equipment and minimise the size of the research teams/people entering the lab, test one participant at a time.
• Putting researchers on alternate air supplies – will require filters/completely separate closed system and associated PPE (to avoid contamination of clothes).
• Consider “symptom-free” washout periods between participants.
• PPE: all of those entering the laboratory may spread virus whilst asymptomatic.
  • The level of PPE required for participant interaction should be based on a risk assessment of the intervention. At all times consider whether an alternate approach is possible that would reduce the risk to researcher and participant.
  • Normally, you should not breach social distancing rules to collect samples. To do so safely would require, at minimum: an apron, gloves and fluid resistant surgical mask (while these are in short supply clinically, you should consider not using them for research), hand washing before and after the intervention.
  • Wearing goggles stops you passing the virus from work surface to hand to eye, and a mask into the mouth. It also limits spread through coughing.
  • Where there is a risk of an Aerosol Generating Procedure. UK guidance suggests an FFP3 mask or equivalent, eye protection, gloves and fluid resistant suit or surgical gown.
  • Face Mask equivalence.
  • A statement on the reusability of masks can be found here.
  • Filtration within breathing systems. HMEF filters remove particles <5micrometres 99.5 % of the time which is sufficient for in-hospital use. The additional benefit of viral filters is to remove 99.9 % of particles <5micrometres. More information here and here.
  • PPE requires a little training and practice to be used effectively, along with designated spaces for donning/doffing. A lot of PPE may be required each day, hence the need to be exacting with its indications for use and to budget for this in research costings.
  • Don and Doff PPE in a way which reduces viral exposure to the researcher and those around them. Guidance here and here.
• Testing of participants for the presence of virus or antibodies to SARS-CoV-2 prior to testing can be considered, but remains controversial, and recovery from infection may not guarantee protection from reinfection or from infecting others. At the time of writing, serological testing cannot be relied upon. More information here.
• Testing of research participants for COVID-19: experience from elsewhere suggests that such testing can only be effectively used for risk stratification rather than a definitive inclusion/ exclusion. As always, the test is only valid at the moment it was taken and not when results are available (which may be up to 2 days later).
• The limitations of the current testing technology are important to consider in the context of using them for risk stratifying participants.
• Some have considered temperature assessments (e.g. IR forehead temperature) of those entering the laboratory. These are not reliable indicators of infection, can result in a lot of false positives, and are unlikely to identify those with asymptomatic or pre-symptomatic disease.
• Have an action plan in place for what to do in the event of a positive test or post-experiment report of infection. In the UK, COVID-19 is a notifiable disease. Hence only certain facilities are allowed to test using the RT-PCR technique. If there is a positive result, there is a large amount of administration. There will also be an element of counselling and signposting that will need to occur, as you now have a formal test result that has implications for the individual, those that have been in close proximity and potential vulnerable people they share a household with. As with other testing/screening protocols information governance processes will need to be adhered too. Particularly as information will be flowing between participant-researcher-testing lab-GP

Decontamination

• Rigorous handwashing and/or use of alcohol gel should be enforced. Hands that are sterile can pick up virus from work surface, the mouth and can immediately be spread – so clean hands at every opportunity. Wipe down all surfaces with viricidal solutions/alcohol wipes when used (e.g. handles on kit, keyboards) and fully clean all surfaces at the end of each testing session and day.
• All equipment should be carefully reviewed to ensure that it can be thoroughly and comprehensively sterilised after use (e.g. check sample lines, turbines, internal gas pathways, Velcro straps etc. can be sterilised).
• Consider using disposable equipment where possible. Dispose of appropriately.
• Use appropriate filters as necessary on all equipment that carries a risk of cross infection.
• Treat anything worn in the laboratory as “infected” and dispose of it carefully before washing hands. Likewise, protective masks should be cleaned (alcohol wipes or soap and water) on removal.
• Decontamination: chlorine-based cleaning solutions have demonstrable ability to clear the virus from surfaces. Soap and water is also effective due to its action disrupting the lipid layer that encases the virus. Current WHO disinfection recommendations include the use of:
  • 70 % Ethyl alcohol to disinfect reusable dedicated equipment (e.g., thermometers) between uses.
  • Sodium hypochlorite at 0.5 % (equivalent 5000 ppm) for disinfection of frequently touched surfaces in homes or healthcare facilities
• Where possible, consider introducing a daily period of high temperature in the climatic chambers to help inactivate the viral load (probably requires at least 45 minutes at 56 °C). More information here.
• More useful guidance here and here.
• Useful guidance on cleaning in non-hospital areas can be found here.

Current recommendations from different laboratories

(NB this includes resources from Slack “Human Research COVID-19” Discussion forum, established by Caroline Rickards)

University of Illinois at Chicago’s current COVID-19 & research statements.

Guidance from Aubun University compliance.docx (posted by Austin Robinson)
What methods may be used to reduce the risk of exposure to COVID-19 if we are unable to maintain a distance, at all times, of at least 6 feet between all persons?
When a distance of 6 feet or more cannot be maintained between the participant and other individuals that may be present, the research team will need to wear appropriate personal protective equipment (PPE):

• N-95 respirator
  • surgical masks or other alternatives are not acceptable for personal protection
  • must be used and maintained in accordance with Risk Management and Safety Guidance
  • fit testing can be provided by Risk Management and Safety (844-4870)

• Eye protection
  • face shield or goggles are appropriate
  • must be cleaned with EPA approved disinfectant after each session

• Gloves
  • disposable type nitrile or natural rubber
  • must be discarded after each session

• Lab coat
  • disposable type
  • must be discarded after each session

Any physical item that participants need to make contact with for the purposes of the research should be decontaminated BEFORE and AFTER each participant. An EPA approved disinfectant must be used

The American Thoracic Society