Remdesivir

Remdesivir is recommended as an option for treating COVID‑19 pneumonitis in hospital in

• adults if they have a high risk of progression to serious illness – see Appendix

• 16-17 year olds with

  • EITHER high risk of progression to serious illness

  • OR requiring supplemental oxygen for any reason

Should be initiated within 7 days of symptom onset.

Dose

IV 200mg STAT on Day 1, followed by 100mg OD for 4 further days (for a total of 5 days)

Contraindication

Not recommended for use if:

• If eGFR less than 30mL/min/1.73m2

• Pregnancy

Caution

Breast feeding – limited information.

If ALT greater than or equal to 5 times the ULN.

Common side effects: Headache; nausea; rash

Consider corticosteroids in patients with evidence of COVID-19 pneumonitis who require supplemental oxygen to maintain prescribed oxygen saturation levels or have a level of hypoxia that needs supplemental oxygen but who are unable to have or tolerate it. Please be aware that Pneumonitis usually occurs at least 7 days after initial COVID-19 infection and that steroids may cause harm if used inappropriately in the early viraemic phase of infection.

Dexamethasone PO 6mg (base) ONCE a day or IV 6.6mg for 10 days or until no oxygen requirement, whichever is sooner (only use intravenous administration when tablets or oral solutions are inappropriate or unavailable)

Or

In pregnant or breastfeeding women Prednisolone PO 40 mg ONCE a day for 10 days or until discharge, whichever is sooner should be used instead of dexamethasone.

Or

Hydrocortisone: 50 mg intravenously every 8 hours for 10 days, (this may be continued for up to 28 days for people with septic shock)

Consider gastroprotection during corticosteroid treatment.

Common side effects: Anxiety; behaviour abnormal; cataract subcapsular; cognitive impairment; Cushing's syndrome; electrolyte imbalance; fatigue; fluid retention; gastrointestinal discomfort; headache; healing impaired; hirsutism; hypertension; increased risk of infection; menstrual cycle irregularities; mood altered; nausea; osteoporosis; peptic ulcer; psychotic disorder; skin reactions; sleep disorders; weight increased.

Tocilizumab

The decision to initiate treatment with Tocilizumab for COVID-19 pneumonitis MUST only be made after discussion with a Respiratory or Microbiology Consultant.

Tocilizumab is indicated in patients who:

• are already receiving systemic corticosteroids.

• AND require either supplemental oxygen or mechanical ventilation.

• AND have no evidence of a bacterial or viral infection (other than COVID-19) that might be worsened by tocilizumab.

NB The efficacy of tocilizumab has not been established in the treatment of COVID-19 in people who do not have elevated C-reactive protein levels. It can be given in conjunction with Remdesivir if required.

Dose: 8 mg/kg ONCE (rounded to the nearest 20 mg). Maximum dose 800mg.

Dose banding is applied to avoid manipulation of part vials and optimise the available stock.

Caution if ALT or AST more than 1.5 x Upper Limit of Normal (ULN).

Contraindication

Not recommended for use if:

• liver enzymes are 10 or more x ULN.

• Absolute neutrophil count of less than 1 x 10⁹/L

• Platelet count of less than 50 x 10³/µL

Common side effects: Abdominal pain; anxiety; conjunctivitis; constipation; cough; diarrhoea; dizziness; dyslipidaemia; dyspnoea; gastrointestinal disorders; headache; hypersensitivity; hypertension; hypofibrinogenaemia; hypokalaemia; increased risk of infection; insomnia; leucopenia; nausea; neutropenia; oral disorders; peripheral oedema; skin reactions; weight increased.

Baricitinib

The decision to initiate treatment with Baricitinib for COVID-19 pneumonitis MUST only be made after discussion with a Respiratory or Microbiology Consultant

Baricitinib may be considered for people with COVID-19 who:

• Need supplemental oxygen for COVID-19 pneumonitis and

• Are having or have completed a course of corticosteroids, unless they cannot have corticosteroids and

• Have no evidence of infection (other than COVID-19) that might be worsened by baricitinib.

When there is clinical deterioration despite treatment with tocilizumab, it may be appropriate to add Baricitinib.

Baricitinib is contraindicated in:

• Known hypersensitivity to Baricitinib;

• eGFR <15 mL/min/1.73m2

• Receiving dialysis or haemofiltration;

• Absolute neutrophil count (ANC) less than 1 x 10⁹ cells/L

• Absolute Lymphocyte Count (ALC) less than 0.5 x 10⁹ cells/L treatment should not be initiated or should be temporarily interrupted. Use clinical judgement as appropriate.

• Haemoglobin less than 8g/dL

• Active or latent tuberculosis

• pregnancy and breastfeeding.

It is good practice to screen for blood borne viruses including HIV, hepatitis B and C prior to starting baricitinib. Doses can be given whilst result are pending. In case of positive result discuss with microbiology.

Common side effects: Abdominal pain; dyslipidaemia; headache; herpes zoster (interrupt treatment); increased risk of infection; nausea; skin reactions; thrombocytosis.

1. National Institute for Health and Care Excellence COVID-19 rapid guideline: managing COVID-19 Last updated: 08 May 2024. Accessed via: https://www.nice.org.uk/guidance/ng191

As defined by the independent advisory group commissioned by the Department of Health and Social Care (June 2023)

Down syndrome and other genetic disorders

All individuals with Down 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 10 ms)

  • severe to moderate iron overload (T2 * greater than or equal to 10 ms) plus an additional comorbidity 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], ATG)

  • an additional substantial risk factor that would in isolation make them eligible for monoclonals or oral antivirals.

• Non-transplant renal patients who have received a comparable level of immunosuppression

• People with chronic kidney disease (CKD) stage 4 or 5 (an estimated glomerular filtration rate [eGFR] less than 30 ml per min per 1.73 m²) 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, ofatumumab, 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 10 mg 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 or relevant COVID test); 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, nervous system or lung inflammation or significantly impaired renal, liver, nervous system 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 30 mg 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 1 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 mm³ and 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, neurodegenerative and neuroimmune 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 neurological disorders

This guideline has been registered with the Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

This guideline is for use in Frimley Health NHS Foundation Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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