The Belgium Task Force released updated interim clinical guidance for adult Belgian patients with suspected or confirmed coronavirus disease 2019 (COVID-19) on March 31, 2020.[1] This summary covers its recommendations for adjunctive antiviral/immunologic treatment and supportive care.
Hospitalized Patients With Suspected COVID-19
Mild-to-moderate symptoms (no dyspnea), not in a risk group
Supportive care: Symptomatic treatment without additional antiviral therapy.
Use acetaminophen as first-line therapy (usual dosage), and cautiously use nonsteroidal anti-inflammatory agents (NSAIDs) (if required).
Mild-to-moderate symptoms (no dyspnea), in a risk group (ie, age > 65 y AND/OR underlying end-organ dysfunction [lung, heart, liver, etc], diabetes, coronaropathy, chronic obstructive pulmonary disease, arterial hypertension); or alarming symptoms (dyspnea)
If possible, discuss case-by-case with an infectious disease specialist to initiate empiric antiviral therapy, based on the potential delay to obtain results (antiviral therapy is expected to be more efficient if started early in the disease course), or on other considerations (high risk of secondary complications).
If the decision is made to treat in-hospital patients empirically, follow the treatment options as described for confirmed cases, below.
Hospitalized Patients With Confirmed COVID-19
Mild-to-moderate disease (no oxygen [O2] requirements/no evidence of pneumonia), in a risk group
Supportive care: symptomatic treatment
Consider starting hydroxychloroquine (Plaquenil), IF NO CONTRAINDICATION, using a regimen of 400 mg at suspicion/diagnosis and 400 mg 12 hours later, followed by 200 mg twice daily (BID) up to day 5.
Note: When patients improve on hydroxychloroquine, delayed hospital discharge is unnecessary; the 5-day course can be completed at home. The hospital should provide the necessary tablets upon discharge.
If no hydroxychloroquine is available: Consider a chloroquine base dose of 600 mg (10 mg/kg) at diagnosis and 300 mg (5 mg/kg) 12 hours later, followed by 300 mg (5 mg/kg) BID up to day 5; or chloroquine phosphate 1,000 mg at diagnosis and 500 mg 12 hours later, followed by 300 mg BID up to day 5.
Contraindications to hydroxychloroquine include a known allergy to the drug.
Note: Pregnancy is not a contraindication as such (large safety experience with chloroquine); assess the risk versus benefit.
Note: Use with caution if renal impairment is present, taking into account the scarcity of pharmacokinetic data. Keep the same loading dose (D1) but decrease the D2-D5 dose to 50% if the glomerular filtration rate (GFR) is between 10 and 30 mL/min, and to 25% if the GFR is <10 mL/min or dialysis.
Perform daily electrocardiography (ECG) if the initial QTc is 450-500 msec, and obtain biochemistry (including potassium level) according to the underlying disease.
Note: Sanofi requests that hydroxychloroquine-related adverse events are reported to Pharmacovigilance.Belgium@sanofi.com.
Note: No sufficient evidence exists about azithromycin activity; therefore, there is currently no reason to associate this antibiotic to hydroxychloroquine treatment.
Precautions: Use caution with hydroxychloroquine in the presence of:
A QTc interval >500 msec
Hypokalemia
Drug interaction(s) (check at https://www.covid19-druginteractions.org/ [University of Liverpool]): The interaction potential of hydroxychloroquine is likely the same as that of chloroquine.
Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
Myasthenia gravis
Porphyria
Retinal pathology
Epilepsy
Uncontrolled diabetes
Severe disease (≥1 of the following: respiratory rate ≥ 30/min [adults] or ≥40/min [children aged <5 y]; blood O2 saturation ≤93%; ratio of partial pressure of arterial O2 to percentage of inspired O2 [PaO2/FiO2] <300; lung infiltrates >50% of the lung field within 24-48 hours]
Supportive care includes the following:
Optimal supportive care in the hospital ward (or intensive care unit [ICU])
Provide O2
Carefully consider administering antibiotics/antifungals, based on the local epidemiology.
Start hydroxychloroquine (Plaquenil), IF NO CONTRAINDICATION, using a regimen of 400 mg at diagnosis, 400 mg 12 hours later, followed by 200 mg BID up to day 5.
Note: When patients improve on hydroxychloroquine, delayed hospital discharge is unnecessary; the 5-day course can be completed at home. The hospital should provide the necessary tablets upon discharge.
Note: If no hydroxychloroquine is available, consider a chloroquine base dose of 600 mg (10 mg/kg) at diagnosis and 300 mg (5 mg/kg) 12 hours later, followed by 300 mg (5 mg/kg) BID up to day 5; or chloroquine phosphate 1,000 mg at diagnosis and 500 mg 12 hours later, followed by 500 mg BID up to day 5.
Consider lopinavir/ritonavir 400/100 mg (= 2 tablets of 200/50 mg) BID for 14 days as a second choice ONLY if hydroxychloroquine/chloroquine are contraindicated, and provided it can be administered within 12 days after symptomatic onset (also check for drug interaction!); or in children <10 kg (after advice from infectious disease specialists).
See the previous section for contraindications and precautions regarding hydroxychloroquine.
Critical disease (≥1 of the following: acute respiratory distress syndrome [ARDS]; sepsis; altered consciousness; multiorgan failure [MOF])
Supportive care includes the following:
Optimal supportive care in the ICU
Mechanical ventilation
Specific ARDS prevention and treatment
Track secondary bacterial and opportunistic (Aspergillus) infections
Prevention of subsequent lung fibrosis
Note: Studies are ongoing regarding dexamethasone, tocilizumab, etc, in this most critical group.
Additional antiviral therapy includes compassionate use of remdesivir: 200 mg intravenous (IV) loading dose (within 30 min) and 100 mg once daily for 2-10 days.
If remdesivir is unavailable, consider (hydroxy)chloroquine crushed in a nasogastric tube, at the same dosage and monitoring as above; replace with remdesivir if it becomes available. Because the clinical efficacy of (hydroxy)chloroquine has not been demonstrated, use caution in the setting of severe cases with kidney/liver/cardiac failure; abstention may be preferred in such situations.
Note: Tocilizumab and other interleukins (IL) (IL-6 or 1) blockers: Some Chinese, Italian, and (very limited) Belgian clinical experience (unpublished) suggest a favorable effect in the most critical patients suffering from persistent and overwhelming inflammation resembling cytokine release syndrome (CRS). However, at present, this class of drugs should only be used in clinical trials or within Belgian/international cohort studies if possible. The drug could be considered on an individual basis in patients with persistent inflammation (ie, elevated IL-6, C-reactive protein [CRP], D-dimers, ferritin, etc) and ARDS requiring mechanical ventilation without evidence of bacterial superinfection/sepsis.
Remdesivir precautions
At present, Gilead has very restricted availability of and very strict criteria for remdesivir (long supply delay). As of March 24, 2020, (outside of clinical trials and expanded access) this drug is restricted to compassionate use for pregnant women and children only. Request at: https://rdvcu.gilead.com/.
Inclusion criteria for remdesivir consists of ICU plus polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) plus mechanical ventilation.
Exclusion criteria for remdesivir include evidence of MOF; need for inotropic agents; a creatinine clearance <30 mL/min, dialysis, or hemofiltration; and levels of transaminases >5 times the upper limit of normal.
Of note, remdesivir is one of the treatment arms in the DisCoVeRy trial.
Limited information on drug interaction(s) is available. Make individual risk-benefit assessments. Close monitoring of remdesivir toxicity or diminished efficacy of concomitant drug(s) is recommended. Also check for remdesivir interaction(s) at https://www.covid19-druginteractions.org/ (University of Liverpool).
For more information, please go to Medscape's Novel Coronavirus (COVID-19) Resource Center.
For more COVID-19 Clinical Guidelines, please go here.
For more Clinical Practice Guidelines, please go to Guidelines.
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Cite this: Belgium Task Force on Supportive Care and Antiviral/Immunologic Treatment of Hospitalized Patients With Suspected or Confirmed COVID-19 (2020) - Medscape - Apr 07, 2020.
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