COVID-19 is a key aim of GenOMICC
Susceptibility to COVID-19 is almost certainly, in part, genetic. GenOMICC can find the genes that cause susceptibility, which may help us to prioritise treatments to respond to the global crisis.
GenOMICCwas designed for this crisis. Since 2016, the open, global GenOMICC collaboration has been recruit patients with emerging infections, including COVID-19. All patients with confirmed COVID-19 in critical care are eligible for GenOMICC; please recruit them as normal, following local infection control precautions.
In particular, we aim to recruit every intubated patient with COVID-19. If you need to prioritise, please start with the youngest.
GenOMICCis prioritised as an NIHR Urgent Public Health Study in the UK
In the UK, recruitment to
GenOMICCwill supplement other studies (e.g. ISARIC 4C, RECOVERY, and REMAP-CAP), enabling better prioritisation of treatments and faster answers. We will co-enrol and combine samples. Telephone consent is allowed, or witnessed consent forms (from outside the PPE area) can be used to record consent.
Who do I recruit?
Please aim to recruit every COVID-19 patient who is invasively ventilated (intubated).
We focus on the youngest and sickest patients first. If you need to prioritise, please start with the youngest patients who are ventilated in your ICU.
If you have time and capacity, we also include a broader range of patients in critical care:
- Our aim is to capture ICU and HDU patients. During the COVID-19 outbreak these patients will be cared for in unusual areas. For this reason, and to enable international comparisons where terms like "ICU" and "HDU" are applied differently, we settled on the catch-all description "requires continuous cardiorespiratory monitoring". Treatment with CPAP or NIV does not always require continuous monitoring so that doesn't meet our criteria on its own.
- We added "or invasive mechanical ventilation" to the criteria because we don't want to miss anyone who is intubated, although of course clinicians will recognise that continuous monitoring is always required in intubated patients.
- Patients not admitted to critical care are not included, even if they are desperately sick
- If a patient meets the inclusion criteria they remain eligible for recruitment for the rest of their lives, even after being transferred out of ICU.
Inclusion / Exclusion decisions
Do we apply exclusion criteria to COVID-19 cases?
No, the exclusion criteria (age/comorbidity) do not apply to COVID-19 cases. Here is a flowchart describing recruitment: The key objective of GenOMICC during COVID-19 is to recruit every intubated COVID-19 case.
requiring continuous monitoring?] -->B B[COVID-19] --> Y A --> C C[Any other eligible diagnosis] --> D D[Free from
pre-existing disease] --> Y Y[Recruit patient to GenOMICC]
Are patients on CPAP or NIV eligible?
Our aim is to capture ICU and HDU patients. During the outbreak these patients will be cared for in unusual areas. For this reason, and to enable international comparisons where terms like "ICU" and "HDU" are applied differently, we settled on the catch-all description "requires continuous cardiorespiratory monitoring". Treatment with CPAP or NIV does not always require continuous monitoring so that doesn't meet our criteria on its own.
We also added "or invasive mechanical ventilation" because we don't want to miss anyone who is intubated, although of course clinicians will recognise that continuous monitoring is always required in intubated patients.
Should I approach the patient/relatives during this time of obvious distress?
The ICU Perspectives Study provides a comprehensive survey of 1400 critically-ill patients/families and staff. They found that people are much happier to be approached about research than staff anticipate.
I have been asked to recruit these patients to another study instead of GenOMICC - what should I do?
We recommend that sites follow the NIHR Urgent Public Health priority list when deciding which patients to include in research studies. According to this process, it has been agreed by the naitonal prioritisation exercise that patients who are critically ill with COVID-19 should be recruited to the GenOMICC study.
The GenOMICC investigators will then share DNA samples and data with other studies as needed to get the fastest possible research studies completed in the best interests of critically ill patients across the country.
Is aspiration pneumonia/hospital-acquired pneumonia included?
No, Hospital acquired pneumonia is also excluded e.g post op pneumonia etc.
If it is not / never sure what the infection is – can they be included?
Yes, diagnoses are always a bit uncertain so we include anyone who, in the best judgement of the treating team, meets the inclusion criteria.
Do pathogens need to be confirmed? Should we wait to recruit until micro is back for suspected flu & RSV patients?
To meet the criteria for flu/RSV, the pathogen needs to be confirmed using routine clincal tests in your hospital (near-patient rapid tests are OK). If the patient presents with primary pneumonia, then they meet the entry criteria even without identifying any pathogen.
What if patient has a positive micro result that was taken prior to day zero (critical care admission)?
Samples predating critical care admission (prior to day zero) can be included in the section 'Presumed Primary infection' if they are the primary cause of the patient's illness.
What is classed as a “quantifiable sterile injury”?
This term is used in the protocol to describe the rationale for the study. Perhaps the best example is burns, in which the injury is sterile (that is, not infectious) and the severity of the initial injury can be accurately measured. For decisions about inclusion, the entry criteria should be applied.
What is the criteria for capacity checks?
Capacity checks are in the view of the treating clinician.
What is classed as functionally limited?
Anyone whose day-to-day function is changed by chronic health problems. For example, many asthmatics are functionally unlimited, but carry inhalers. Others are breathless on exertion, and hence have some functinal limitation. This does not apply to COVID-19 cases - all ICU patients with COVID-19 are included.
For survivors of COVID-19 that we could not get consent/assent earlier – can we recruit now?
Yes. We can recruit patients at any time after they meet the criteria - on the ward, in out-patient clinics, even at home if feasible.
There are non-COVID-19 patients in the ICU that are eligible for GenOMICC, are you currently still interested in recruiting these patients?
Yes, thank you.
How do you get samples from patients in isolation areas (e.g. with COVID-19)?
We've been asking sites to follow their own local procedures for blood sampling. The EDTA blood for genetics can be taken with routine bloods, or as a special collection. We suggest labelling and bagging the tubes at the bedside, and then using gloved hands to put this bag into a second bag, which is then placed into the specimen transport box. The specimen transport box should be kept separate from the contamination zone. The samples are handled by our lab staff using gloves at this end.
You mention a unique code in the protocol for blood samples. Is this the trial ID number? How are ID numbers allocated?
The GenOMICC ID numbers are generated by us and sent to you in the sample packs. Each strip of 4 sticky labels represents one patient. Multiple labels are provided in case you provide blood in multiple tubes. Please discard any unused labels. Please enter this number in the RedCAP form exactly as it appears on the sticky label.
How should I affix the barcode to the tube?
Please place the barcode along the tube, not around. This makes it easier for the laboratory staff to scan it.
Can blood & saliva samples be stored over the weekend or do they need to be refrigerated, if so at what temperature?
Both blood and saliva can be stored at room temperature for up to 7 days before arriving in our lab.
Our EDTA tubes fall just short of the 9mls required. Is 8mls acceptable?
Yes, 8mls is fine.
Do we have to use a certain size/type of EDTA blood tubes?
No, any EDTA blood tubes can be used. The total volume of blood sent back to GenOMICC should be as close to 9ml as possible.
Do sites have to do anything now or in the future for repeat sampling?
No. This part of the study is intended to recruit very carefully-selected patients on a small scale, where local infrastructure exists. We will contact you directly about this if necessary.
Is the GP letter just for repeat sampling patients?
RedCAP says: Only record samples taken within the first 3 calendar days from admission to ICU (day 0). What does that mean exactly?
Day zero = day of critical care admission. So if a patient is admitted on Monday, then record samples taken within the first 3 calendar days. e.g. Monday - Tuesday - Wednesday
Do the samples need to be returned via courier?
No. The specimen transport boxes that we provide are UN3373 Biological Substance Category-B approved packaging, and can be used to send the blood samples to us via Royal Mail. This is in line with PHE guidance for transport of COVID-19 patient samples. Samples should be double bagged and dropped into the clean specimen box which is kept separate from the contamination zone. Extra bags (along with an additional biohazard label) are provided within the specimen boxes.
Is there a lab manual?
No – samples are sent to Edinburgh for all processing.
How do I obtain a blood sample and can I use invasive lines?
Yes. An appropriately-trained individual can obtain peripheral venous, central venous, or arterial blood for GenOMICC according to local policies.
Who is considered the patients “consultee”?
This is the patients representative, next of kin, or other appropriate individual who can make a competent assessment of the decision to participate, on behalf of the patient.
Do you have consent forms in languages other than English?
No - Only English at the moment.
Regained capacity consent. If the patient leaves hospital prior to regaining capacity or they are missed prior to discharge, how do we get regained capacity consent?
We expect this scenario to be rare. Patients who do not regain capacity before hospital discharge are unlikely to ever regain capacity. If there is a reasonable expectation that a patient may regain capacity after discharge, we would ask that you create a pragmatic arrangement in discussion with the relevant carers and the patient's consultee. This may include occasional contact from the research team. In those circumstances you can decide how often to make contact, based on your clinical expectation of how rapidly it is likely that the patient might recover capacity.
Our patient does not have next of kin only a probation officer. Is there an approach we are allowed to take in these very rare cases?
The local PI should determine if a probation officer is the most appropriate person to obtain consent on behalf of the participant. If no one else is available then this is allowed according to HRA guidelines under the Mental Capacity Act.
The Mental Capacity Act says that consultees for intrusive research other than Clinical Trials of Investigational Medicinal Products (CTIMPs), in England and Wales are:
A personal consultee, i.e. a person who cares for the adult lacking capacity or is interested in that person's welfare, but is not doing so for remuneration or acting in a professional capacity.
A nominated consultee i.e. a professional who is independent of the study, can do so if a personal consultee is not available or is unwilling to give advice.
There is further provision for emergency situations.
How is the GenOMICC patient I.D number generated?
We'll tell you these: you'll find them on the sample labels in the sample postage boxes which each site has been provided with.
RedCAP asks me to enter a GenOMICC ID, where do I find this?
These numbers are generated by us and found on the sticky labels provided in the sample boxes. Please enter the full number code including numbers and letters exactly as it appears on the sticky label.
What is the national database audit number?
ICNARC number in England/Wales or SICSAG number in Scotland. These numbers are assigned to patients upon their admission to intensive care.
Is GenOMICC on the portfolio?
Yes - we have received confirmation that GenOMICC is eligible for NIHR CRN support and is an NIHR Urgent Public Health Priority study.
How many patients in total are being recruited?
What is the start/end date?
GenOMICC is already recruiting. The end date for the study is 31/08/29
Are you using a delegation log or collecting CVs from participating staff
No, GenOMICC is not a regulated study so no delegation log is necessary. We collect the PI's CV at each site, but no other CVs. Each PI is responsible for delegating recruitment activity at their site and can record delegation to whole teams of research staff without specifically recording the name of each team member.
Who is going to be credited/recognised in publications resulting from GenOMICC?
Regarding authorship, we will adhere to the policy here.
Are you only recruiting prospectively?
Any patient who has met our entry criteria at any time in their life is eligible for inclusion in the study. These will require individual consent and sampling, so they will count as accruals. However we are not at the moment able to provide funding to sites to search through clinical/audit databases for patients who met GenOMICC criteria and have now been discharged (retrospective recruitment). We do hope to do this in the future, subject to funding. Our reason for focusing on prospective recruitment is that we can also recruit nonsurvivors if we recruit prospectively.
Recruitment of survivors: are you interested in receiving survivor samples as per the protocol?
We are recruiting in hospitals only at the moment (patients who may or may not survive). We may in the future recruit retrospectively (survivors who were not recruited in hospital) but we are not doing this yet.
Protocol says that repeat sampling will be done from a subset of critical illness survivors - are you as the sponsor letting us know which patients are required to be invited back for repeat sampling?
The sub-study involving repeat sampling will be co-ordinated and run from Roslin.
Is co-enrolment allowed with other studies?
We encourage co-enrolment with other studies, including interventional studies.
How early in a ICU admission would blood samples need to be obtained?
The sample can be obtained at any time, and we don't want to put patients, relatives or research staff under excessive pressure. However, since we're studying immediately life-threatening conditions, earlier recruitment is desirable to maximise the number of very severe cases we can recruit.
Are blood samples processed at the recruiting site?
No processing of any kind is needed. Whole blood is shipped at ambient temperature. We will provide the packaging.
Are blood bottles provided for sample collection?
We are able to provide blood tubes to sites if necessary and we recognise that this is an unfunded component of the study. However most hospitals have been happy to agree to provide a small number of EDTA (full blood count) tubes from their normal clinical stock. Click here for examples of tubes to use.
Is professional consent allowed from medic independent from the research ?
This fits with our protocol as long as the initial approach is made by a member of the clinical team.
What follow up is carried out via telephone and at what time point? How long is this likely to take?
Follow-up is limited to mortality outcomes and late micro results. In our experience so far, it usually takes less than 30mins to complete the whole process.
How is screening done?
We have tried to make this as light as possible - no screening log is needed, and the simple screening criteria for COVID-19 are very easy indeed to apply: recruit every intubated COVID-19 case.