Non-hospitalised patients with symptomatic COVID-19 infection (Guidelines)

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.

Consider ONLY once initial eligibility and exclusion criteria are met

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.

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.

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.

Nirmatrelvir plus ritonavir (Paxlovid®)

There are no human data on the use of 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 nirmatrelvir plus ritonavir (Paxlovid®).  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 nirmatrelvir plus ritonavir(Paxlovid®).

Remdesivir

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).

Molnupiravir

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.

Sotrovimab

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 nirmatrelvir plus ritonavir, Paxlovid®), remdesivir, molnupiravir and sotrovimab as published on www.medicines.org.uk/emc website.

Nirmatrelvir plus ritonavir (Paxlovid®)

There is a risk of serious adverse reactions due to interactions with other medicinal products (see https://www.covid19-druginteractions.org/checker).

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 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 nirmatrelvir plus ritonavir (Paxlovid®).
• Loss of therapeutic effect of 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 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.

• Please refer to current COVID-19 vaccination guidance in: the Green Book, Immunisation Against Infectious Disease (chapter 14a).
• Further information is available at: Liverpool COVID-19 interactions 

Nirmatrelvir plus ritonavir (Paxlovid®):

300mg (two x 150mg tablets) 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) 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 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 nirmatrelvir plus ritonavir(Paxlovid®), the patient should complete the full 5-day treatment course at the discretion of the admitting consultant.

Remdesivir:

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.

Molnupiravir:

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.

Sotrovimab:

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.

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 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

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.

No interaction is expected between sotrovimab, 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: https://www.covid19-druginteractions.org/prescribing-resources

Any suspected adverse reactions from treatment with sotrovimab, 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: https://coronavirus-yellowcard.mhra.gov.uk/.

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).

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). This list has been updated by DHSC on 5^th April 2023 and can be found here.

Box 1 Risk factors for progression to severe COVID‑19 in adults

Risk factors for progression to severe COVID‑19 in adults defined by the independent advisory group commissioned by the Department of Health and Social Care (June 2023)

Down’s syndrome and other genetic disorders

All individuals with Down’s Syndrome or other chromosomal disorders known to affect immune competence.

Solid cancer

• metastatic or locally advanced inoperable cancer
• lung cancer (at any stage)
• people receiving any chemotherapy (including antibody-drug conjugates), PI3K inhibitors or radiotherapy within 12 months
• people who have had cancer resected within 3 months and who received no adjuvant chemotherapy or radiotherapy
• people who have had cancer resected within 3 to 12 months and receiving no adjuvant chemotherapy or radiotherapy are expected to be at less risk (and thus less priority) but still at increased risk compared with the non-cancer populations

Haematological diseases and recipients of haematological stem cell transplant (HSCT)

• Allogeneic HSCT recipients in the last 12 months or active graft versus 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 CAR-T cell therapy in the last 24 months, or until the lymphocyte count is within the normal range
• Individuals with haematological malignancies receiving systemic anti‑cancer treatment (SACT) within the last 12 months, or radiotherapy in the last 12 months
• all people who do not fit the criteria above, and are diagnosed with:
  • myeloma (excluding monoclonal gammopathy of undetermined significance (MGUS))
  • AL amyloidosis
  • chronic B-cell lymphoproliferative disorders (chronic lymphocytic leukaemia, follicular lymphoma)
  • myelodysplastic syndrome (MDS)
  • chronic myelomonocytic leukaemia (CMML)
  • myelofibrosis
  • any mature T-cell malignancy
• all people with sickle cell disease
• people with thalassaemia or rare inherited anaemia with any of the following:
  • severe cardiac iron overload (T2 * less than 10ms)
  • severe to moderate iron overload (T2 * greater than or equal to 10ms) plus an additional co-morbidity of concern (for example, diabetes, chronic liver disease or severe hepatic iron load on MRI)
• individuals with non-malignant haematological disorders (for example, aplastic anaemia or paroxysmal nocturnal haemoglobinuria) receiving B-cell depleting systemic treatment (for example, anti-CD20, anti-thymocyte globulin (ATG) and alemtuzumab) within the last 12 months

Renal disease

• renal transplant recipients (including those with failed transplants within the past 12 months), particularly those who have:
  • received B cell depleting therapy within the past 12 months (including alemtuzumab, rituximab [anti-CD20], anti-thymocyte globulin)
  • an additional substantial risk factor which would in isolation make them eligible for monoclonals or oral antivirals
• non-transplant renal patients who have received a comparable level of immunosuppression
• patients with chronic kidney stage (CKD) 4 or 5 (an estimated glomerular filtration rate (eGFR) less than 30ml per min per 1.73m²) without immunosuppression

Liver diseases

• people with cirrhosis Child-Pugh (CP) class A,B and C, whether receiving immune suppressive therapy or not. Those with decompensated liver disease (CP B and C) are at greatest risk
• people with a liver transplant
• people with liver disease on immune suppressive therapy (including people with and without cirrhosis)

Solid organ transplant recipients

Solid organ transplant recipients not in any of the above categories.

Immune mediated inflammatory disorders

(diseases in which autoimmune or autoinflammation-based pathways are implicated in disease, for example, inflammatory arthritis, connective tissue diseases, inflammatory skin diseases, inflammatory gastrointestinal disease)

• people who have received a B-cell depleting therapy (anti-CD20 drug for example, rituximab, ocrelizumab, ofatumab, obinutuzumab) in the last 12 months.
• people who have been treated with cyclophosphamide (IV or oral) in the 6 months prior to positive PCR or relevant COVID test
• people who are on corticosteroids (equivalent to 10mg or more per day of prednisolone) for at least the 28 days prior to positive PCR or relevant COVID test
• People who are on biologics or small molecule JAK inhibitors
• people who are on current treatment with mycophenolate mofetil, oral tacrolimus, azathioprine, mercaptopurine, or similar agents (for major organ involvement such as kidney, gastro-intestinal tract, liver, lung, brain), methotrexate (for interstitial lung disease or asthma only) and/or ciclosporin. No minimum dose threshold is suggested
• People who are on current treatment (or within the last 6 months) with S1P modulators (fingolimod, ponesimod or siponimod), or alemtuzumab or cladribine within the last 12 months
• people who exhibit at least one of: (a) uncontrolled or clinically active disease (that is, required recent increase in dose or initiation of new immunosuppressive drug or IM steroid injection or course of oral steroids within the 3 months prior to positive PCR); and/or (b) other high risk comorbidities (for example, body mass index (BMI) greater than 30, diabetes mellitus, hypertension, major organ involvement such as significant kidney, liver or lung inflammation or significantly impaired renal, liver and/or lung function)

Respiratory

• asthma in people on oral corticosteroids (defined above). Any asthma patient taking immunosuppressants for their asthma including but not exclusively methotrexate, ciclosporin. Frequent exacerbations requiring 4 or more courses of prednisolone per year, usually 40 mg per day for 5 days or more
• COPD on long term home non-invasive ventilation (NIV). Patients on long term oxygen therapy. People with moderate or severe disease (FEV1 less than or equal to 50% predicted) who have required 4 or more courses of prednisolone 30mg for 5 days or greater in last 12 months
• interstitial lung disease (ILD) - all patients with idiopathic pulmonary fibrosis
• sub-types of ILD - for example, connective tissue disease related, sarcoidosis, hypersensitivity pneumonitis, NSIP (non specific interstitial pneumonia) who have received a B-cell depleting therapy in last 12 months, or IV or oral cyclophosphamide in the 6 months prior to testing positive for COVID-19. Any ILD patient on current treatment with corticosteroids, mycophenolate mofetil, azathioprine, tacrolimus, cyclosporin or methotrexate. No minimum dose criteria
• any people with any type of ILD who may not be on treatment due to intolerance but has severe disease with an FVC predicted less than 60%
• NIV and tracheostomy ventilated - all patients requiring this type of support regardless of the underlying disorder (which might include COPD, obesity hypoventilation syndrome, scoliosis, bronchiectasis, neurodisability and genetic muscular diseases [refer to neurology section])
• lung cancer patients, refer to ‘Solid cancer’ section above
• lung transplant patients (refer to solid organ transplant section)
• pulmonary hypertension (PH): groups 1 and 4 from PH classification

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 or autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED syndrome)
• primary immunodeficiency associated with impaired type I interferon signalling
• x-linked agammaglobulinaemia (and other primary agammaglobulinaemias)
• any person with secondary immunodeficiency receiving, or eligible for, immunoglobulin replacement therapy

HIV/AIDS

• people with high levels of immune suppression, have uncontrolled or untreated HIV (high viral load) or present acutely with an AIDS defining diagnosis
• people on treatment for HIV with CD4 less than 350 cells per mm³and stable on HIV treatment or CD4 greater than 350 cells per mm³ and additional risk factors (for example, age, diabetes, obesity, cardiovascular, liver or renal disease, homeless, alcoholic dependency)

Neurological disorders

• Conditions associated with neuromuscular respiratory failure requiring chronic ventilatory support:
  • motor neurone disease
  • Duchenne muscular dystrophy
  • Conditions that require use of specific immunotherapies:
    • multiple sclerosis (MS)
    • myasthenia gravis (MG)
    • other immune mediated disorders
• Dementia and neurodegenerative disorders when associated with severe frailty (for example, levels 7 or 8 on Clinical Frailty Scale, as part of a personalised care plan):
  • Alzheimer’s disease, vascular disease, Lewy body disease, or frontotemporal atrophy
  • Parkinson’s Disease
  • Huntington’s disease
  • progressive supranuclear palsy and multiple system atrophy
  • motor neurone disease
  • multiple sclerosis and other immune-mediated nerological disorders

Box 2: Risk factors for progression to severe COVID‑19 in young people aged 12 to 17 years

Pathway for PCR (or relevant COVID test) positive symptomatic cases aged older than 12 and younger than 18 years, greater than 40 kg weight, and clinical concern: defined by the independent advisory group commissioned by the Department of Health and Social Care (March 2023)

Children and young people (CYP) at substantial risk

• Complex life-limiting neurodisability with recurrent respiratory infections or compromise.

CYP at significant risk if 2 or more or these risk factors are present:

Primary immunodeficiency:

• common variable immunodeficiency (CVID)
• primary antibody deficiency on immunoglobulin (or eligible for immunoglobulin replacement)
• hyper-IgM syndromes
• Good’s syndrome (thymoma plus B-cell deficiency)
• severe combined immunodeficiency (SCID)
• autoimmune polyglandular syndromes or autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED syndrome)
• primary immunodeficiency associated with impaired type I interferon signalling
• x-linked agammaglobulinaemia (and other primary agammaglobulinaemias)

Secondary immunodeficiency:

• HIV CD4 count less than 200 cells per mm³
• solid organ transplant
• HSCT within 12 months, or with GVHD
• CAR-T therapy in last 24 months
• induction chemotherapy for acute lymphoblastic leukaemia (ALL), non-Hodgkin’s lymphoma, chemotherapy for acute myeloid leukaemia (AML), relapsed and/or refractory leukaemia or lymphoma

Immunosuppressive treatment:

• chemotherapy within the last 3 months
• cyclophosphamide within the last 3 months
• corticosteroids greater than 2mg per kg per day for 28 days in last 4 weeks
• B cell depleting treatment in the last 12 months

Other conditions:

• high BMI (greater than 95th Centile)
• severe respiratory disease (for example, cystic fibrosis or bronchiectasis with FEV1 less than 60%)
• tracheostomy or long-term ventilation
• severe asthma (PICU admission in 12 months)
• neurodisability and/or neurodevelopmental disorders
• severe cardiac disease
• severe chronic kidney disease
• severe liver disease
• sickle cell disease or other severe haemoglobinopathy
• trisomy 21
• complex or chromosomal genetic or metabolic conditions associated with significant comorbidity
• multiple congenital anomalies associated with significant comorbidity
• bronchopulmonary dysplasia - decisions should be made taking in to account degree of prematurity at birth and chronological age

Footnotes:

1. This advice is gathered from evidence in people over 18 years - risks for those under 18 years are summarised in Box 2.
2. Physician discretion is advised for each of the conditions provided and decision to treat should follow evaluation of individual circumstances.
3. Please refer also to IMID section.
4. IMIDs comprise diseases in which auto-immune or auto-inflammation based pathways are implicated in disease for example, inflammatory arthritis, connective tissue diseases, inflammatory skin diseases, inflammatory gastrointestinal disease.
5. Please cross refer to the ‘Respiratory’ section in Box 1.
6. The IAG gave detailed consideration to the risks posed by TNF inhibitors and other cytokine inhibitors, including JAK inhibitors, used in rheumatology, dermatology and gastroenterology practice. As detailed in the appendix, there is consistent evidence of reduced serology responses in a variety of IMIDs to some these medications, but little consistent evidence as yet of increased severity of outcomes upon infection.
7. Please cross reference to advice in the sections on in Box 1 on IMIDs, solid cancer and neurology. Note also advice regarding glucocorticoids in evaluation in IMID section.
8. Note, exceptionally, that frequent exacerbations requiring 4 or more courses of prednisolone per year, usually 40mg per day for 5 days or more, may render an asthma patient eligible.
9. Patients using continuous positive airway pressure (CPAP) only for treatment of obstructive sleep apnoea (OSA) are not deemed to be particularly high risk and do not require prioritised access to treatments for COVID-19 disease.
10. Refer to respiratory section for details.
11. The use of CD4 counts to assess eligibility for treatment applies only to those patients for whom CD4 counts are used to monitor for treatment compliance and/or levels of immune compromise. Where CD4 counts are not known, but concerns remain around potential immune compromise, discussion with the patient’s HIV team is advised.
12. These should be managed according to the recommendations contained in the broader section on immune-mediate inflammatory disorders with the individual drugs - for example, rituximab, ocrelizumab, used as the ‘gatekeeper’, rather than the specific diagnosis.
13. For example, levels 7 or 8 on Clinical Frailty Scale, as part of a personalised care plan.
14. Complex congenital heart disease and severe bronchopulmonary dysplasia are rare and as such do not offer a readily available dataset upon which to base advice. As such, we propose a practical approach to adopt clinical criteria similar to those used to administer palivizumab for respiratory syncytial virus (RSV) prevention in the same groups of very young infants. Where clinical judgement of other individual patient circumstances not covered above strongly suggests that prophylaxis would prevent serious outcome upon SARS-CoV-2 infection in infants who are at particular risk of complications from this virus, use of appropriate antiviral approaches should be considered by an MDT.

• additional prescribing resources on University of Liverpool COVID-19 Drug Interactions website
• Includes evaluating the interaction risk, assessing a patient for treatment with nirmatrelvir plus ritonavir (Paxlovid®) and guidance for resuming paused or dose-adjusted co-medications.