**Laboratory workshop** This workshop was designed to highlight changes that have occurred from a laboratory perspective, as a result of the COVID-19 pandemic. This session covers three main areas of interest, including the safe handling and processing of clinical samples, new assay requirements during and post COVID-19 and the impact of COVID-19 on ECMC lab organisation. **Panel** - Debora Joseph-Pietras – Southampton - ECMC senior research fellow - Tony Price -Manchester- Head of QA for CRUK NI of cancer biomarker centre - Ultan Power – Belfast- Prof of molecular virology - Bill Greenhalf – Liverpool - Director of GCP facility - David Jamieson – Newcastle- Head of pharmacogenomics/biomarker assays - Fiona Thompson – Glasgow- Head of ECMC lab - Ingunn Holen – Sheffield- ECMC science lead - Kienan Savage – Belfast- ECMC science lead **Safe handling and processing of samples** - In May 2020 Public Health England (PHE) released guidelines regarding the safe handling and processing of samples. SARS-CoV-2 is classed as a Hazard Group 3 pathogen and under normal circumstances would require laboratory work to be conducted at containment level 3 (CL3). However, working at this level could result in severe disruptions for the diagnostic sector. Therefore, a risk-based proportionate approach has been adopted, allowing certain laboratory activities to be undertaken at CL2, so long as samples are processed in a microbiology safety cabinet (MSC) and the sample processing does not generate aerosols. Laboratory staff should be familiar with these PHE guidelines (https://www.gov.uk/government/publications/wuhan-novel-coronavirus-guidance-for-clinical-diagnostic-laboratories/wuhan-novel-coronavirus-handling-and-processing-of-laboratory-specimens). - Any propagation, culturing or deliberate work on SARS-CoV-2 for diagnostic/research purposes must be carried out at CL3. - Although samples can be processed in a MSC it may not be feasible to do certain procedures such as microscopy or use specific equipment, which cannot be held within a CL2 cabinet. Under these circumstances, providing that samples are processed/inactivated in a MSC then it is acceptable to do certain procedures on the bench e.g. blood cell counts. - SARS-CoV-2 RNA has been found in a wide range of clinical samples including blood, faeces, cerebrospinal fluid and tissue samples. Viral RNA can be detected in saliva and faecal samples after respiratory swabs are no longer positive for the virus, with detection in faeces up to 47 days following the onset of symptoms. Although the infectious potential of these samples has not been established, it is best practice to treat these samples as infectious. - It has been shown that SARS-CoV-2 can be cultured from paper. Therefore, the paperwork accompanying samples from COVID-19 patients should be treated as infectious. Several ECMC labs have biological handling processes in place for paperwork, quarantining the physical pieces of paper from COVID-19 ‘hot’ wards for 48 hours, before they are handled by the lab staff. - Sharing of best practice regarding handling of SARS-CoV-2 samples between academic labs and NHS clinical sites within ECMC North has been conducted during the pandemic. However, it is important that these practices are only used as guidelines, as each site must work within their local risk assessments and regulations. What is appropriate for one site, may not be appropriate for another. - If a patient is subsequently found to be COVID-19 positive after the samples have been taken, it is best practice to inform the relevant lab. However, there are no formal guidelines in place. **New assay requirements during and post covid:** - Viral infection can initiate an immune response, subsequently signalling for the recruitment of different immune cells and the release of cytokines. In a dysfunctional immune response, this can lead to a cytokine storm. Asymptomatic (COVID-19) patients have shown to have higher levels of inflammatory markers than control (COVID-19 negative) patients. Asymptomatic patients may have a higher/more active innate immune response early in the infection, resulting in a localised infection to the respiratory system. - It is important to understand to what extent COVID-19 infection can impact the results of immunological assays such as neutrophil to lymphocyte ratios, immunotherapy response assays and cytokine assays. These assays are routinely conducted on samples from cancer patients, therefore if COVID-19 infection does influence these assays it may contribute to an artificially higher immune response not related to cancer/cancer treatment. - It is unknown to what extent the viral load contributes to the severity of an immune response. Studies have shown that adults and children have a similar viral load, but there is high inter-individual variability in immune response. The viral load that a patient is initially exposed to may impact the severity of the COVID-19 infection. However, the relationship between viral load and infectivity is currently unknown. Therefore, regardless of the sample viral load (low, medium or high), samples should be treated as infectious. - This inflammatory response principle is likely to be similar for a variety of respiratory viruses, but there will be specific elements attributed to COVID-19 infection. This highlights the requirement to investigate other respiratory viruses such as influenza, as they may have a similar impact on immunological assays. **Impact of COVID-19 on ECMC lab organisation:** - The rapid lockdown during the first wave of the COVID-19 pandemic in the UK resulted in many labs closing promptly in March 2020, before a gradual reopening in June 2020. This had a negative impact on cancer studies in the UK, resulting in the suspension of sample analysis and many clinical trials. Re-opening of the labs was not without its challenges, as many groups have faced budget cuts and reduced staffing due to shielding, re-deployment and furlough. - Labs have had to adapt in order to safely facilitate sample processing/analysis under new restrictions. This includes having well ventilated labs, wearing appropriate PPE and reducing the number of social interactions in the workplace (e.g. tea/coffee breaks in communal space). - One of the key adaptions groups have made is having staff trained on multiple techniques so that there is suitable cross-cover. In addition, many ECMC labs have reduced capacity (50% or less) and adopted ‘shift work’ or ‘bubbles’ to minimise the number of staff required to isolate should a staff member test positive. Together these processes are required to ensure that the essential lab work can be carried out with minimal disruption. - A blended working environment (i.e. home and the lab) has been implemented for many teams, conducting tasks at home not require physical presence in laboratories, such as emails, paper work and meetings. However, one of the main initial challenges associated with home working was finding the appropriate infrastructure to support home working for entire labs. This demonstrates the requirement to invest in suitable IT infrastructure to support home working during this pandemic and for potential future pandemics. - The NHS contact-tracing app has created issues regarding isolation notifications, particularly for clinical labs. In many Trusts, when PPE is worn then the contact tracing app is often ‘switched off’ to reduce the incidences of false notifications (‘Mask on, App off policy’). The app should be used when PPE is not worn and the device that app is on should be with you. There have been incidences where devices have been left in lockers/drawers during a shift, resulting in the notification of isolation even though there was no direct contact between individuals.