The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19
Condition: SARS-CoV-2 Infection
MeSH terms: COVID-19
Study type: Interventional

Summary: 
      The Lateral Flow Antigen Validity and Applicability (LAVA) 2 study aims to determine the
      validity of lateral flow antigen devices (LFDs) used to perform point of care testing for
      COVID-19, compared to the current gold standard test of RTPCR in children. In a pilot study
      we have shown that the anterior nose swabs used to perform a LFD test are associated with
      significantly lower pain scores than the nose and throat swabs used to perform RT-PCR tests
      and that the results are available significantly more quickly. RT-PCR is an excellent
      diagnostic test but one drawback includes remaining positive for a prolonged period,
      potentially when the person is no longer infective, as it can pick up viral particulate
      rather than live virus. LFDs are more likely to be positive at the point that a person has a
      high viral load and is therefore infectious to others, but this has not been studied in
      non-laboratory settings in children. The study aims to determine the correlation between LFD
      and viral load detected on RT-PCR in children to enable the utility of the test in different
      clinical and non-clinical settings to be better determined.
    

Detailed description: 
      Purpose and Design This study aims to answer key questions about testing for COVID-19 in
      children. COVID-19 in children is very different from adults: COVID-19 infection is less
      prevalent in children compared to adults and the disease course is very much milder, with
      children being more likely to be asymptomatic than adults. Currently, all children admitted
      to hospital or undergoing a procedure under general anaesthetic are routinely tested for
      SARS-CoV-2 using RT-PCR performed on a nose and throat swab. Whilst this is an excellent
      diagnostic test for someone who is symptomatic with COVID-19, it can remain positive for a
      significant period after a person has been infected with COVID-19 and is no longer a risk to
      others. In a clinical setting this can result in elective operations being cancelled,
      potentially unnecessarily. Additionally, it means that children who may be infective with
      COVID-19 are less likely to be symptomatic with the infection, indeed many patients who have
      been diagnosed with COVID-19 have been admitted to hospital for an unrelated cause, making
      differentiation on the basis of symptoms difficult. We have chosen to look primarily at the
      relationship between lateral flow device tests performed on anterior nasal swabs, which are a
      less painful swab and give a rapid result, compared to the viral load detected using RT-PCR
      performed on a nose and throat swab. This will complement ongoing work which is being
      performed outside of the group proposing this study, which is examining the relationship
      between viral load and infectivity. This study will be able to determine the performance of
      the LFD at different viral loads and therefore the utility of the LFD within clinical
      settings to predict which patients are infective with SARS-CoV-2.

      The study has been designed by a multidisciplinary team, described in the steering group.
      Unfortunately due to the need to deliver this study rapidly, patient and parental input has
      not been specifically sought but the pain scores described in the pilot study work display
      the acceptability of this test to parents.

      Recruitment and consent In order to recruit a sufficient number of patients to answer the
      study question in a timely way, as is required, we have built into the protocol the option to
      take deferred consent to participate in the study. The acceptability of the swabs is clear
      within the pilot study and the test is being widely used in community settings already.
      Deferred consent is not felt to be appropriate for children in the peri-operative period due
      to the impact that it may have on their clinical care and therefore patients and families
      will be approached about the study before the swab is performed. In all other settings, a
      routine swab for SARS-CoV-2 is being performed anyway which is more painful for the child
      than the study swab.

      The specificity of the LFD has been shown to be very good (99.6%) in laboratory and clinical
      settings and therefore employing the use of the LFD within the study may also enable
      hospitals to detect asymptomatic infective children with COVID-19 earlier in their admission.
      A recording of the patients who are approached before a routine swab is performed but who
      decline the test will be kept to ensure that a swab is not performed anyway with the
      assumption that they will be approached for deferred consent. The record will include the
      child's hospital number and the parent's email address. No additional details will be held.
      Patients will be approached for consent by being emailed a small amount of information about
      the study with a link to the PIS followed by a link to the consent form, with the option to
      record refusal of consent if they do not wish to participate. The appropriate PISC will be
      sent according to whether they are approached before or after the anterior nose swab has been
      taken. The person emailing the patients the PISC does not have to be GMP trained, but should
      a patient or their family wish to ask questions they will have the details of the study
      team's telephone number and email address. Inclusion/exclusion This study is intended to
      include all children under 18 years of age who are undergoing routine swabbing or who are
      having a procedure performed under general anaesthetic. Risks, burdens and benefits Having
      undertaken the pilot study we have had opportunity to understand the impact on patients and
      their families.

      Many patients and parents were positive about participating in the study, appreciating the
      opportunity to have an additional test prior to an operation and getting the results of the
      LFD test back more quickly. As shown in the pilot study, the pain scores given by children
      and parents were significantly lower using anterior nasal swabs compared to nose and throat
      swabs suggesting that there is much higher acceptability of the test. Some participants did
      refuse to participate because they were concerned that their child may find an additional
      swab distressing or because they did not want to run the risk of a long-awaited elective
      procedure being cancelled. During the pilot study we found no adverse events associated with
      the anterior nasal swabs and given the lower pain scores seen, can reassure parents that the
      swab required for the LFD is significantly less painful for a child. Confidentiality We are
      collecting the hospital number of each patient to enable accurate tracking of patients within
      the study. These will be visible to the central study team but each site's patients will only
      be visible to patients within that site. The first half of the postcode is being collected
      because subsequent analysis of the positive predictive value of the test requires the
      prevalence of COVID-19 to be known. The DOB and sex of the child is being collected so that
      the demographics of the patients included in the study are known, enabling appropriate
      conclusions to be drawn. CAG approval has not been sought as the COPI notice issued by the
      Secretary of State allows the appropriate collection of data within studies focussed on
      COVID-19 to be collected and can include people who do not sit within the direct care team to
      contribute to the recruitment and running of the study. Conflict of interest None of the
      study group have any declared conflict of interest in the study. The results will be given to
      Public Health England and will be submitted for peer review and subsequent publication.
    

Intervention name(s): Innova Lateral Flow Test
Intervention type(s): Diagnostic Test
Intervention description(s): Lateral flow test performed on anterior nasal or buccal swabs
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic