On 12 January 2020, a novel coronavirus was identified as the cause of an outbreak of
unexplained pneumonia in Wuhan City, Hubei Province, China. This coronavirus was later named
SARS-CoV-2, and the disease it causes COVID-19.

SARS-CoV-2 is a non-segmented, positive sense RNA virus and part of the family of
coronaviruses. Similar to the Systemic Acute Respiratory Syndrome (SARS) virus, it binds to
the angiotensin-converting enzyme 2 (ACE2) receptor located on type II alveolar cells and
intestinal epithelia. SARS-CoV-2 can result in a severe Acute Respiratory Distress Syndrome
(ARDS) which is characterised by diffuse alveolar damage and direct viral cytopathic effect
on pneumocytes. Some patients who develop COVID19 may respond with a fulminant "cytokine
storm" reaction.

As of 23 March 2020, a total of 374,921 COVID-19 cases have been reported in 168 countries
with a total of over 16,411 deaths (case fatality amongst confirmed cases of 4.4%) (John
Hopkins's Coronavirus Resource centre). Over 293,425 cases and 13,258 deaths have been
reported from countries outside mainland China. The World Health Organisation (WHO) declared
on the 12th of March the SARS-CoV-2 outbreak a pandemic in the context of a Public Health
Emergency of International Concern (PHEIC) [4]. Europe has rapidly become the epicentre of
the pandemic and in the UK, cases are increasing daily. There have been 6,724 confirmed cases
in the UK as of 23 March 2020, including 190 confirmed inpatients at St George's Hospital NHS
Trust (23 March 2020 , Dr. Breathnach, personal communication).

Because of the lack of a validated serological test, the actual number, and therefore the
proportion, of people that develop asymptomatic infection remains unknown. This means that an
accurate case fatality estimate remains elusive. Due to the rise in the number of diagnostic
samples, tests are taking longer than expected. Among the foremost priorities to facilitate
public health interventions is a reliable laboratory diagnosis. Prompt case ascertainment is
necessary to ensure rapid and effective contact tracing, implementation of infection
prevention and control measures according to WHO recommendations, and collection of relevant
epidemiological and clinical information.

Because of the lack of a validated serological test, the actual number, and therefore the
proportion, of people that develop asymptomatic infections remains unknown. This means that
an accurate case fatality estimate remains elusive. Due to the rise of the number of samples
to diagnose, tests are taking longer than expected. Among the foremost priorities to
facilitate public health interventions is a reliable laboratory diagnosis. Prompt case
confirmation is necessary to ensure rapid and effective contact tracing, implementation of
infection prevention and control measures according to WHO recommendations, and collection of
relevant epidemiological and clinical information.

The experience in China has been that around 15% of patients with confirmed infection develop
severe disease and around 5% become critically ill. In the UK, a modelling analysis by the
Imperial College COVID-19 Response Team suggests that even with the implementation of
self-isolation measures (household quarantine and social distancing) the surge limits for
both general wards and ICU beds will be exceeded 8-fold. Furthermore, a relaxation of these
mitigation measures is likely to lead to a rebound of cases until there is an effective
vaccine - which is not expected for some 12-18 months. We can therefore clearly expect a
significant number of inpatients with COVID-19 infection in the UK in the coming months.

The SARS-CoV-2 antigen and antibody lateral flow assay (LFA) development has been led by
Mologic, a company based in Bedford. We will use prototype LFA and ELISA that are ready for
preliminary evaluation, and subsequently use these tests on-site to evaluate the test at POC.
LFA have been developed for SARS-CoV-2 antigen detection in throat/ nose swabs and detection
of IgG and IgM in blood/serum and SARS-CoV-2 antigen detection, IgG, IgM and IgA in saliva.
Saliva is an exciting sample to use as it is far easier to use than blood or throat / nose
swabs for potential self-testing.

Additionally, it is currently unknown why some patients develop severe COVID-19, while others
affected by the same SARS-CoV-2 infection display only mild symptoms. Co-morbidities such as
hypertension, kidney disease and diabetes have been linked to poorer prognosis and clinical
outcomes. However, a proportion of patients of younger age and without comorbidities also
develop severe disease- and there is a need for greater understanding of the
immunopathogenesis of severe COVID-19 infection is important.

The use of diagnostics developed within this study will improve the management of cases of
COVID-19. The LFA are rapid, easy to use and designed to be affordable globally. The rapid
diagnosis of SARS-CoV-2 with antigen detection will allow patients to be rapidly triaged in
hospital, GP surgeries and other places such as immigration areas. They are sufficiently
cheap to be appropriate for use in low- and middle-income countries. The use of antibody
detection will allow both for diagnosis of immunological response to acute infections as well
as after patients have recovered later . To utilise these tests appropriately an
understanding of dynamic immunopathological changes over time is necessary.

Characterisation of immune response and susceptibility and its association with viral
clearance and disease progression on in large cohorts with varied disease severity is
important to assist clinical risk prediction outcomes and evaluate the potential for novel
immunotherapeutic interventions. Immune response characteristics may have predictive and
prognostic value, with early adaptive immune responses possibly correlated with improved
clinical outcomes.