Non-hospitalised patients with symptomatic COVID-19 infection


Please direct patient enquiries about COVID treatments to or to NHS Highland single point of contact 0800 085 1558.

nMABs are synthetic monoclonal antibodies that bind to the spike protein of SARS-CoV-2, preventing subsequent entry of the virus into the host cell and its replication. This effectively ‘neutralises’ the virus particle. Antiviral medications inhibit viral replication and prevent progression of infection. Recent evidence suggests that antivirals and neutralising monoclonal antibodies (nMABs) significantly improve clinical outcomes in non-hospitalised patients with COVID-19 who are at high risk of progression to severe disease and/or death. The CMO letter published on 28th November 2022 details the interim clinical commissioning policy, on which this guidance is based.  WHO has produced a document "Therapeutics and COVID-19: Living guideline" which is incorporated in the national guidance.  The following products have been granted a conditional marketing authorisation by MHRA for the treatment of non-hospitalised patients with COVID-19:

Place in therapy


Notes on use

First line

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®)*


Second line


PF-07321332 (nirmatrelvir) plus ritonavir are unsuitable

Third line


Only if PF-07321332 (nirmatrelvir) plus ritonavir OR remdesivir are unsuitable

By exception 


If 1st, 2nd and 3rd line treatments not suitable or contra-indicated AND MDT assessment recommends use.  

The evidence (and references) supporting each therapy can be accessed via the clinical commissioning document.

From the evidence referenced in the national policy document, the reduction in hospitalisation or death for each drug is detailed in the table below. Note that disease progression continued for a small group of patients, despite early therapy.


Risk of hospitalisation/death

Patient cohort notes

Active treatment


PF-07321332 (nirmatrelvir) plus ritonavir *



Included non-hospitalized, high risk adults

(Data not yet published in peer reviewed journal)




Excluded vaccinated patients and cancer/immunocompromised underrepresented




Excluded vaccinated patients but included active cancer (2% of participants)


WHO recommends against using sotrovimab as efficacy against newer circulating variants is diminished



*Note: PF-07321332 (nirmatrelvir) plus ritonavir has a number of significant drug interactions and ALL current medication being taken by the patient (hospital or GP prescribed, purchased over the counter or online, herbal or illicit products) MUST be checked using the following website

Administration of nMAB or antiviral does NOT exempt the patient from existing self-isolation rules.  Administration of nMAB is NOT a substitution for vaccination against SARS-CoV-2.

Eligibility Criteria

Initial Eligibility Criteria (must meet all)

SARS-CoV-2 (COVID-19) infection confirmed by either

  • polymerase chain reaction (PCR) test OR
  • Lateral flow test (registered via or NHS 119)


Symptomatic* with COVID-19 and showing no sign of clinical recovery


A member of a highest risk group as defined in appendix 1 (see also note below **)

*Symptoms include: feverish, chills, sore throat, cough, shortness of breath or difficulty breathing, nausea, vomiting, diarrhoea, headache, red or watery eyes, body aches, loss of taste or smell, fatigue, loss of appetite, confusion, dizziness, pressure or tight chest, chest pain, stomach ache, rash, sneezing, sputum or phlegm, runny nose.

** Patients aged between 12 and 17 years should be assessed by a paediatric multi-disciplinary team with input from infectious diseases to determine clinical capacity to benefit from the treatment.  See section on paediatrics.


Exclusion criteria (must not meet any)

  • Requirement for hospitalisation for COVID-19 infection
  • New requirement for supplemental oxygen for COVID-19 symptom management
  • Known hypersensitivity to the active ingredient or any excipients of the medications as listed in the Summary of Product characteristics


Where patients are ineligible for treatment under this policy, recruitment to the PANORAMIC trial, which is building the evidence for novel oral antivirals in a broader cohort of at risk patients, should be supported.

Drug Specific eligibility and exclusion criteria

Consider ONLY once initial eligibility and exclusion criteria are met

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) (1st line,  5 day oral course)


Clinical judgement deems that an antiviral is the preferred option

AND       Treatment is commenced within 5 days of symptom onset

                       (may be extended to 7 days if clinically indicated but off-label)

AND       The patient does NOT have a history of stage 3 to 5 chronic kidney disease

                      (requires MDT discussion with specialist)

AND       PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) treatment has been deemed safe

                       following guidance from the appropriate specialty team(s) – see

              Full drug history must be taken.


  • Children aged less than 18 years
  • Pregnancy
  • The patient is taking medication which has a clinically significant drug interaction with PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) as listed on
  • Severe renal impairment (eGFR less than 30ml/min)
  • Advanced decompensated liver cirrhosis


Remdesivir (2nd line, 3 day IV infusion course)


Clinical judgement deems that an antiviral is the preferred option and the patient is willing to attend daily for three days for IV infusion

AND       Treatment with PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) is contra-indicated or not possible

AND       Treatment is commenced within 7 days of symptom onset


  • Children weighing 40kg and under

If the patient deteriorates clinically and requires admission for supplemental oxygen, they may be considered for treatment with remdesivir for 5 days according to the guidance for hospitalised patients.

Molnupiravir (3rd line, 5 day oral course)


Treatment with sotrovimab, PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) AND remdesivir are  contra-indicated or not possible

AND         Treatment is commenced within 5 days of symptom onset (may be extended to 7 days if clinically indicated but off-label)


  • Children aged less than 18 years
  • Pregnancy


Sotrovimab (4th line, single IV infusion)
  • Endorsement of treatment has been sought and approved by a relevant MDT
  • AND Treatment is commenced within 5 days of symptom onset
    • (may be extended to 7 days if clinically indicated but off-label)
  • Children aged less than 12 years
  • Adolescents (aged 12 to 17 years) weighing 40kg and under

See also appendix 2 for a flowchart and decision support for therapies plus a summary of treatment advice by speciality for the highest risk patients.

Highest risk group in paediatrics

In children and young people (aged under 18yr), risks of hospitalisation or death from COVID are very low. Current evidence suggests that children and young people in the highest risk groups in the national policy (see table in appendix 1 of this policy) do not have equivalent risk to older adults with the same conditions.

Studies of pre-hospital nMAbs and/or anti-virals have largely been in adults and there are minimal data to assess benefit of nMAbs to those under 18yr, even in symptomatic inpatients. Due to low numbers of severely unwell children and young people, it is challenging to estimate the risks vs benefit, or number needed to treat to prevent hospitalisation, and severe disease. Administration of an intravenous or subcutaneous drug to children and young people in hospital brings its own burden, and requires specialised paediatric teams. Nevertheless, equity of care for those deemed to be at risk is vital.

All children and young people who potentially are eligible through the national policy should therefore be discussed with regional paediatric infectious diseases service to confirm eligibility and to consider the risk / benefit and whether to proceed with offer of treatment.

For NHS Highland patients, please refer paediatric patients to the local paediatric team in Inverness or Glasgow, according to the established specialist input for the patient.

Each case will be considered by a national MDT and the paediatric consultant will liaise with the national team to determine if treatment is required.

Pregnancy and women of child-bearing potential

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®)

There are no human data on the use of PF-07321332 (nirmatrelvir) plus ritonavir during pregnancy to inform the drug-associated risk of adverse developmental outcomes, women of childbearing potential should avoid becoming pregnant during treatment with PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®).  PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) is not recommended during pregnancy and in women of childbearing potential not using effective contraception.  Use of ritonavir may reduce the efficacy of combined hormonal contraceptives.  Patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during treatment and until after one complete menstrual cycle after stopping PF-07321332 (nirmatrelvir) plus ritonavir(Paxlovid®).


There are no or limited amount of data from the use of remdesivir in pregnant women. Remdesivir should be avoided in pregnancy unless clinicians believe the benefits of treatment outweigh the risks to the individual (please see SmPC for further information).


There are no data from the use of molnupiravir in pregnant women. Studies in animals have shown reproductive toxicity. Molnupiravir is not recommended during pregnancy. Individuals of childbearing potential should use effective contraception for the duration of treatment and for 4 days after the last dose of molnupiravir.


There are no data from the use of sotrovimab in pregnant women. The SmPC for sotrovimab states that sotrovimab may be used during pregnancy where the expected benefit to the mother justifies the risk to the foetus.


Please refer to the summary of product characteristics for PF-07321332 (nirmatrelvir) plus ritonavir(Paxlovid®), remdesivir, molnupiravir and sotrovimab as published on website.

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®): there is a risk of serious adverse reactions due to interactions with other medicinal products (see

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) is a CYP3A inhibitor so co-prescription with other drugs metabolised by the same pathway may increase or decrease concentrations of PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) or the co-prescribed drug.

These interactions may lead to:

  • Clinically significant adverse reactions, potentially leading to severe, life-threatening or fatal events from greater exposures of concomitant medicinal products.
  • Clinically significant adverse reactions from greater exposures of PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®).
  • Loss of therapeutic effect of PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) and possible development of viral resistance.

Hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) to patients with pre-existing liver diseases, liver enzyme abnormalities or hepatitis. Patients should be advised of possible gastro-intestinal side-effects of treatment - anti-emetics that are not contra-indicated may be considered.  

Remdesivir: hypersensitivity reactions including infusion-related and anaphylactic reactions have been observed during and following administration of remdesivir. Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnoea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. Patients should be monitored for hypersensitivity reactions during and following administration of remdesivir as clinically appropriate. If signs and symptoms of a clinically significant hypersensitivity reaction occur, administration of remdesivir should be discontinued immediately and appropriate treatment initiated. Patients receiving remdesivir in an outpatient setting should be monitored according to local medical practice.

Molnupiravir: the most common adverse reactions (≥1% of subjects) reported during treatment and during 14 days after the last dose of molnupiravir were diarrhoea (3%), nausea (2%), dizziness (1%) and headache (1%) all of which were Grade 1 (mild) or Grade 2 (moderate).

Sotrovimab: hypersensitivity reactions, including serious and/or life-threatening reactions such as anaphylaxis, have been reported following infusion of sotrovimab. Hypersensitivity reactions typically occur within 24 hours of infusion. Signs and symptoms of these reactions may include nausea, chills, dizziness (or syncope), rash, urticaria and flushing. If signs and symptoms of severe hypersensitivity reactions occur, administration should be discontinued immediately and appropriate treatment and/or supportive care should be initiated. If mild to moderate hypersensitivity reactions occur, slowing or stopping the infusion along with appropriate supportive care should be considered.

COVID-19 vaccines

Please refer to current COVID-19 vaccination guidance in the Green Book, Immunisation Against Infectious Disease (chapter 14a).

Further information is available on the following sites:

Liverpool COVID-19 interactions and

Interactions information for COVID-19 vaccines – SPS - Specialist Pharmacy Service – The first stop for professional medicines advice

Dose and administration and patient information leaflets

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®):

300mg (two x 150mg tablets) PF-07321332 (nirmatrelvir) PLUS 100mg (one x 100mg tablet) ritonavir taken together orally twice daily for 5 days  

In moderate renal impairment (eGFR between 30 and 60 mL/min), dose is 150mg (one x 150mg tablets) PF-07321332 (nirmatrelvir) PLUS 100mg (one x 100mg tablet) ritonavir taken together orally twice daily for 5 days.  If a reduced dose is required, the dispenser should remove the extra PF-07321332 tablets from the blister to ensure the correct dose will be taken and explain the alteration to the patient.  An additional information leaflet should be given to the patient to explain the reduced dose (appendix 3). Clinicians should assure themselves that patients are able to swallow the oral tablets and understand the dosing regimen.   A patient information leaflet from the manufacturer is included with the medicines supplied. 

A missed dose should be taken as soon as possible and within 8 hours of the scheduled time, and the normal dosing schedule should be resumed. If more than 8 hours has elapsed, the missed dose should not be taken and the treatment should resume according to the normal dosing schedule.

If a patient requires hospitalisation due to severe or critical COVID-19 after starting treatment with PF-07321332 (nirmatrelvir) plus ritonavir(Paxlovid®), the patient should complete the full 5-day treatment course at the discretion of the admitting consultant.


200mg by IV infusion on day 1 followed by 100mg by IV infusion on days 2 and 3

Each dose should be diluted in either a 250ml (200mg dose) or 100ml (100mg dose) pre-filled bag of 0.9% sodium chloride solution and infused over a minimum of 30 minutes.  The dose should be given at the same time each day.


800mg (four x 200mg capsules) orally twice a day for 5 days 

No dose alteration is required in renal or hepatic impairment.  The treatment course is supplied as 200mg hard capsules which are each 22mm in length and should be swallowed whole with a glass of water and not crushed, chewed or opened. There is no alternative formulation for patients with swallowing difficulties.  Patients should complete the whole course of treatment to reduce the possibility of emerging resistance, even if their symptoms improve.  Advice for missed doses:

  • It is important that patients do not miss or skip doses of this medicine.
  • If the patient forgets to take a dose within 10 hours of the time it is usually taken, they should take it as soon as possible and take the next one at the usual time.
  • If the patient forgets to take a dose by more than 10 hours, they should not take the missed dose and instead take the next one at the usual time.
  • Do not take a double dose to make up for a missed dose.

The patient should be directed to read the manufacturer’s patient information leaflet provided with the medicines AND given a copy of the MHRA leaflet highlighting the information in relation to pregnancy (appendix 4). 

If a patient requires hospitalisation due to severe or critical COVID-19 after starting treatment with molnupiravir, the patient should complete the full 5-day treatment course at the discretion of the admitting consultant.


500mg single dose by IV infusion over 30 minutes
No dose alteration is required for renal or hepatic impairment although the drug has not been studied in patients with severe renal or hepatic impairment. Please see appendix 8 3 for a clinical worksheet detailing the preparation and administration information. Patients should be monitored for 30 minutes after the infusion is complete. The patient should be given the paper information leaflet supplied with the drug (appendix 9 4). Administration should be under taken in areas where management of severe hypersensitivity reactions, such as anaphylaxis, is possible.

Patient Assessment, Supply Information and Stock Holding

Patients who test PCR or lateral flow device (LFD) positive will be directed to the NHS Highland single point of contact phone number as detailed on NHS Inform.  An initial review will take place to check eligibility for treatment, patient location and need for immediate medical assistance.  If the eligibility criteria are met, details will be phoned and emailed to the Flow Navigation Team who will phone the patient to discuss and agree the most appropriate therapy using clinical triage and sent form (appendix 5).   Prescriptions for an oral antiviral (PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) or molnupiravir) will be completed electronically and emailed to the most appropriate stock holding location.  This will be a  hospital prescription form for Raigmore or Lorn and Islands (appendices 6, and 7) plus a screen shot of the ADASTRA episode of care.   A phone call to alert that area will be required, including arrangements for delivery of the oral antiviral to the patient.  Contact information for locations in Argyll and Bute has been shared with the Flow Navigation Team.  

For future reference, the completed ADASTRA episode of care will automatically be uploaded to SCi Store and a copy sent to the patient’s GP practice once it is closed.

Sotrovimab: currently, sotrovimab is available for administration in Raigmore Hospital and Lorn and Islands Hospital only.  This will be reviewed regularly for consideration of adding other centres in the future. Although this remains part of the national recommendations, it is not being recommended for use locally, in accordance with WHO recommendations. Please see the note at the top of this TAM entry

PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®) stocks are held in a number of locations across NHS Highland to facilitate timely access to treatment. This will also be reviewed in light of improved understanding of the demand for these treatments throughout NHS Highland.

Remdesivir: stocks are held in the same hospital locations as sotrovimab and reviewed regularly as above.

Molnupiravir: stocks are held in a number of locations across NHS Highland to facilitate timely access to treatment. This will also be reviewed in light of improved understanding of the demand for these treatments throughout NHS Highland.

Co-administration with other therapies for COVID-19

No interaction is expected between sotrovimab, PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®), remdesivir or molnupiravir and corticosteroids, tocilizumab/sarilumab (IL-6 inhibitors) or remdesivir.  For further information please refer to the University of Liverpool COVID-19 Drug Interactions website

A flow chart to aid assessing a patient for treatment with Paxlovid is available as a prescribing resource on this website:

Safety reporting

Any suspected adverse reactions from treatment with sotrovimab, PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®), remdesivir or molnupiravir should be reported directly to the MHRA via the new dedicated COVID-19 Yellow Card reporting site at:

Outcome reporting

The Deputy Chief Medical Officer recommends that data on all patients with COVID-19 should be captured through the ISARIC 4C Clinical Characterisation Protocol (CCP) case report forms (CRFs), as coordinated by the COVID-19 Clinical Information Network (CO-CIN) (link to forms).

Appendix 1: Patient prioritisation cohorts

Patient cohorts considered at highest risk from COVID-19 and to be prioritised for treatment with nMABs.  The following patient cohorts were determined by an independent advisory group commissioned by the Department of Health and Social Care (DHSC).



Down’s syndrome

Patients with Down’s syndrome

Patients with a solid cancer

  • Active metastatic cancer and active solid cancers (at any stage)
  • Patients receiving chemotherapy within the last 3 months
  • Patients receiving group B or C chemotherapy 3 to 12 month prior
  • Patients receiving radiotherapy within the last 6 months

Patients with haematological diseases and stem cell transplant recipients

  • Allogeneic haematopoietic stem cell transplant (HSCT) recipients in the last 12 months or active graft vs host disease (GVHD) regardless of time from transplant (including HSCT for non-malignant diseases) 
  • Autologous HSCT recipients in the last 12 months (including HSCT for non-malignant diseases)
  • Individuals with haematological malignancies who have
    • received chimaeric antigen receptor (CAR)-T cell therapy in the last 24 months, or
    • radiotherapy in the last 6 months 
  • Individuals with haematological malignancies receiving systemic anti-cancer treatment (SACT) within the last 12 months except patients with chronic phase chronic myeloid leukaemia (CML) in molecular response or first or second line tyrosine kinase inhibitors (TKI).
  • All patients with myeloma (excluding MGUS) or chronic B-cell lymphoproliferative disorders (e.g. chronic lymphocytic leukaemia, follicular lymphoma) or myelodysplastic syndrome (MDS) who do not fit the criteria above.
  • All patients with sickle cell disease.
  • Individuals with non-malignant haematological disorder (e.g. aplastic anaemia or paroxysmal nocturnal haemoglobinuria) receiving B-cell depleting systemic treatment (e.g. anti-CD20, antithymocyte globulin [ATG] and alemtuzumab) within the last 12 months.

Patients with renal disease

  • Renal transplant recipients (including those with failed transplants within the past 12 months), particularly those who:
    • Received B cell depleting therapy within the past 12 months (including alemtuzumab, rituximab [anti-CD20], anti-thymocyte globulin)
    • Have an additional substantial risk factor which would, in isolation, make them eligible for nMABs or oral antivirals
    • Not been vaccinated prior to transplantation
  • Non-transplant patients who have received a comparable level of immunosuppression
  • Patients with chronic kidney stage (CKD) 4 or 5 (an eGFR less than 30 ml/min/1.73m2) without immunosuppression

Patients with liver disease                                                            

  • Patients with cirrhosis Child’s-Pugh class B and C (decompensated liver disease).
  • Patients with a liver transplant
  • Liver patients on immune suppressive therapy (including patients with and without liver cirrhosis)
  • Patients with cirrhosis Child’s-Pugh class A who are not on immune suppressive therapy (compensated liver disease)

Patients with immune-mediated inflammatory disorders (IMID)

  • IMID treated with rituximab or other B cell depleting therapy in the last 12 months
  • IMID with active/unstable disease on corticosteroids, cyclophosphamide, tacrolimus, ciclosporin or mycophenolate.
  • IMID with stable disease on either corticosteroids, cyclophosphamide, tacrolimus, ciclosporin or mycophenolate.
  • IMID patients with active/unstable disease including those on biological monotherapy and on combination biologicals with thiopurine or methotrexate

Primary immune deficiencies

  • Common variable immunodeficiency (CVID)
  • Undefined primary antibody deficiency on immunoglobulin (or eligible for Ig)
  • Hyper-IgM syndromes
  • Good’s syndrome (thymoma plus B-cell deficiency)
  • Severe Combined Immunodeficiency (SCID)
  • Autoimmune polyglandular syndromes/autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED syndrome)
  • Primary immunodeficiency associated with impaired type I interferon signalling
  • X-linked agammaglobulinaemia (and other primary agammaglobulinaemias)
  • Any patient with a secondary immunodeficiency receiving, or eligible for, immunoglobulin replacement therapy


  • Patients with high levels of immune suppression, have uncontrolled/untreated HIV (high viral load) or present acutely with an AIDS defining diagnosis
  • On treatment for HIV with CD4 <350 cells/mm3 and stable on HIV treatment or CD4>350 cells/mm3 and additional risk factors (e.g. age, diabetes, obesity, cardiovascular, liver or renal disease, homeless, those with alcohol-dependence)

Solid organ transplant recipients

All recipients of solid organ transplants not otherwise specified above

Rare neurological conditions

  • Multiple sclerosis
  • Motor neurone disease
  • Myasthenia gravis
  • Huntington’s disease

Appendix 2: Therapy flow chart with decision support and treatment advice by speciality for highest-risk patients

Appendix 3: Patient information leaflet for Paxlovid® reduced dose in renal impairment

Appendix 4: MHRA Additional Patient Information Leaflet oral molnupiravir

Appendix 5: Clinical triage and consent form

Appendix 6: Hospital prescription form for PF-07321332 (nirmatrelvir) plus ritonavir (Paxlovid®)

Appendix 7: Hospital prescription form for molnupiravir

Appendix 8: Clinical worksheet for preparation and administration of sotrovimab

Appendix 9: Sotrovimab patient information leaflet

Further resources

Last reviewed: 15 February 2023

Next review: 31 January 2024

Author(s): COVID-19 Working Group

Version: 3

Approved By: TAM subgroup of the ADTC

Reviewer Name(s): Alison MacDonald, Area Antimicrobial Pharmacist

Document Id: COVID111

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