Inclusion Criteria:

1. Aged 18-30 years on proposed date of enrolment.

2. Body Mass Index (BMI) ≥18.5 kg/m2and ≤28 kg/m2.

3. In good health with no history of clinically significant medical conditions (as
described in Exclusion criteria) that would interfere with subject safety, as
defined by medical history, physical examination, routine laboratory tests,
cardiovascular magnetic resonance imaging or echocardiogram, ECG, pulmonary function
tests and Chest X-Ray as determined by the Investigator at a screening evaluation.

4. Volunteer is willing and able to give written informed consent for participation in
the study

5. Willing to allow the investigators to discuss the volunteer's medical history with
their General Practitioner or any relevant health authority

6. Allow the investigator to register volunteer details with a confidential database
(The Over-volunteering Prevention Service) to prevent concurrent entry into clinical
studies/trials

7. Agreement to refrain from blood donation during the course of the study

8. a. For women of child bearing potential (WOCBP), a willingness to practice
continuous effective contraception during the study and, a negative pregnancy test
on the day(s) of screening and challenge b. b. For women of child bearing potential
(WOCBP) taking the combined oral contraceptive pill, a willingness to use barrier
contraception with spermicide during treatment with Paxlovid and for 30 days after
completing Paxlovid treatment (should they receive it).

9. Able and willing (in the investigator's opinion) to comply with all study
requirements

10. No clinically relevant findings in medical history or on physical examination in the
opinion of a clinically qualified investigator, in discussion with the CI if needed

11. For Groups 1 & 2: Previous microbiological confirmation of SARS-CoV-2 infection > 3
months prior to enrolment (Proof of positive PCR or lateral flow antigen test
confirmed via medical notes/ or UK HSA or a history from a volunteer consistent with
SARS-CoV-2 infection with other evidence of this infection such as a photograph of a
positive lateral flow test on the volunteer's phone or similar) OR serological
confirmation such as positive anti-nucleocapsid IgG serology (unless this is
explainable by prior vaccination) with the most recent history of symptoms or
exposure likely to represent SARS-CoV-2 infection having occurred > 3 months prior
to enrolment.

12. For Groups 3 & 4: Written or electronic evidence of at least one vaccination against
SARS- CoV-2 >21 days prior to enrolment (proof required would include written or
electronic evidence from GP/ medical records or electronic NHS COVID pass) where no
history of symptoms or exposure can be identified to determine the timing of
SARS-CoV-2 infection, volunteers may be enrolled >7 weeks from the identification of
anti-nucleocapsid positivity and >3 months from their last negative
anti-nucleocapsid antibody test.

Exclusion Criteria:

1) History or evidence of any clinically significant or currently active
cardiovascular, (including thromboembolic events), respiratory (excluding SARS CoV-2
infection), dermatological, gastrointestinal, endocrine, haematological, hepatic,
immunological, rheumatological, metabolic, urological, renal, neurological or
psychiatric illness. Specifically:

1. Volunteers with any history of physician diagnosed and/or objective test confirmed
asthma, chronic obstructive pulmonary disease, pulmonary hypertension, reactive
airway disease, or chronic lung condition of any aetiology or who have experienced:

i) Significant/severe wheeze in the past ii) Clinically significant respiratory
symptoms including wheeze which has ever resulted in hospitalisation iii) Known
bronchial hyper reactivity to viruses

2. History of thromboembolic, cardiovascular or cerebrovascular disease

3. History or evidence of diabetes mellitus (Type I or Type II)

4. Any concurrent serious illness including history of malignancy that could interfere
with the aims of the study or a subject completing the study. Basal cell carcinoma
within 5 years of treatment or with evidence of recurrence is also an exclusion.

5. Migraine with associated neurological symptoms such as hemiplegia or vision loss.
Cluster headache/migraine or prophylactic treatment for migraine

6. History or evidence of clinically significant autoimmune disease or known
immunodeficiency of any cause (including HIV).

7. History of severe psychiatric illness at any time (e.g. inpatient stay, psychosis)
or current significant active symptoms of anxiety and/or depression or significant
claustrophobia. Consider exclusion in the following cases:

i) Volunteers with history of anxiety related symptoms of any severity within the
last 2 years if the Generalized Anxiety Disorder-7 score is ≥5 ii) Volunteers with a
history of depression of any severity within the last 2 years if the Patient Health
Questionnaire-9 score is ≥4 iii) Significant claustrophobia

8. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or
prior history of significant bleeding or bruising following injections or
venepuncture.

9. Other major disease that, in the opinion of the Investigator, could interfere with a
subject completing the study and necessary investigations.

2) Clinically significant smoking history. Defined as: Current smoker (any smoking
including e-cigarettes in the last 3 months) or > 2 pack year smoking history at any
time (2 pack years is equivalent to 20 cigarettes daily for 2 years), or use of any
nicotine containing products, on more than one occasion, within the last 3 months.

3) History or presence of alcohol addiction, or excessive use of alcohol (average
weekly intake in excess of 28 units alcohol; one unit being a half glass of beer, a
small glass of wine or a measure of spirits)

4) Clinically significant history of use of drugs of misuse, with evidence of a
negative drugs of misuse urine test required at screening and quarantine admission

5) History of anaphylaxis or any allergy likely to be worsened by any component of the
study agent or proposed treatment regime.

6) Clinically active rhinitis (including hay fever) or history of moderate to severe
rhinitis, or history of seasonal allergic rhinitis likely to be active at time of
inclusion into the study and/or requiring regular nasal corticosteroids on at least
weekly basis, within 30 days of admission to quarantine.

7) Any significant abnormality altering the anatomy of the nose or nasopharynx,
clinically significant history of epistaxis (nose bleeds) or any nasal or sinus
surgery within six months of inoculation

8) Clinical, radiological, or laboratory evidence of current active TB disease or
latent TB infection

9) Previous VZV pneumonia

10) Positive HBsAg, HCV or HIV antibodies

11) Concurrent use of oral, inhaled or systemic steroid medication or use within the
last 6 months (steroids used as a cream or ointment are permissible), or the use of
other immunosuppressive agents concurrently or within the last 6 months.

12) Concurrent use of medication contraindicated for use with Paxlovid rescue therapy

13) Administration of immunoglobulins and/or any blood products within the three months
preceding the planned study challenge date

14) Current use of any medication or other drug taken through the nasal or inhaled route
including cocaine or other recreational drugs

15) Plans to receive a live vaccination 30 days prior to enrolment, or any vaccination
(i.e. non-live, including a SARS-CoV-2 vaccine) 21 days prior to enrolment and/or
plans to take any vaccination 30 days following enrolment

16) Current pregnancy or pregnancy within the last 6 months, lactation or intention to
become pregnant during study period

17) Shares a household with someone with clinically significant immunodeficiency (due to
underlying medical condition, medication or pregnancy); or who is extremely
clinically vulnerable (previously shielding under Public Health England (now
referred to as UK HSA) guidelines)

18) Concurrent participation in another research study involving receipt of an
investigational product in the 30 days preceding enrolment, or planned use during
the study period

19) Laboratory confirmed (PCR or lateral flow antigen test) SARS-Cov-2 infection,
evidence of viral pneumonitis on chest radiograph or a high clinical suspicion of
COVID-19 disease in the 3 months preceding enrolment.

20) Post COVID-19 symptoms that have not resolved by 1 month prior to enrolment

21) Previous hospitalisation with COVID-19 disease or related complications e.g.
pulmonary fibrosis on chest x ray

22) Family history of 1st degree relative aged 50 years or less with sudden cardiac or
unexplained death

23) Family history of severe COVID-19 disease or response to any other viral disease
e.g. Guillain-Barré

24) Family history unavailable or in opinion of investigators not sufficient to assess
criteria 22 and 23.

25) Clinically significant abnormality on screening chest radiograph

26) Clinically significant abnormality of lung function testing

27) Clinically significant structural heart disease detected on CMR or echocardiogram,
such as abnormal ventricular systolic function, evidence of previous myocardial
infarction, previous myocarditis (on CMR) or significant valvular heart disease
(more than mild)

28) Any clinically significant abnormality of screening blood or urine tests

29) Any other significant disease, disorder, or finding, which, in the opinion of the
investigator, may either put the volunteer at risk, affect the volunteer's ability
to participate in the study or impair interpretation of the study data

30) Venous access deemed inadequate for the phlebotomy and cannulation demands of the
study.

For Groups 3 & 4:

31) Previous positive test for SARS CoV-2 infection (PCR or lateral flow antigen test)
or a high clinical suspicion of COVID-19 disease at any time.

32) Positive Anti-nucleocapsid IgG at screening, unless explainable by vaccination