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Table 3 Summary of national guidelines in the use of investigational adjunctive treatments in COVID-19

From: Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines

Severity of COVID-19
(WHO classification)
NHC (China)SIMIT Lombardy section (Italy)SWAB (Netherlands)Sciensano (Belgium)
MildSymptomatic treatment
Other general treatments:
• Interferon-alpha (5 million units or equivalent dose added to 2 ml sterile water, delivered via nebulizer bid)
• Lopinavir-ritonavir (400 mg/100 mg bid; not > 10 days)
• Ribavirin (500 mg bid/tid, not > 10 days)(recommended in combination with interferon or lopinavir-ritonavir)
• Chloroquine phosphate (500 mg bid for 7 days in adults 18–65 years and body weight > 50 kg; 500 mg bid for days 1–2, followed by 500 mg od for days 3–7 in adults < 50 kg)
• Umifenovir (200 mg tid, not > 10 days)
Symptomatic treatment
In age > 70 years old and/or co-morbidities
• Consider lopinavir-ritonavir (400 mg/ 100 mg bid) + Chloroquine (500 mg bid) or HCQ (200 mg bid) for 5–20 days)
Alternatives to lopinavir-ritonavir:
• Darunavir + ritonavir (800 mg/ 100 mg od), or
• Darunavir + cobicistat (800 mg/ 150 mg od)
Symptomatic treatmentSymptomatic treatment
• Consider starting HCQ (400 mg at diagnosis, then 400 mg 12 h later, followed by 200 mg bid up to day 5)
or
• chloroquine base (10 mg/kg at diagnosis, 5 mg/kg 12 h later, followed by 5 mg/kg bid up to day 5)
or
• chloroquine phosphate (1000 mg at diagnosis, then 500 mg bid, followed by 300 mg bid up to day 5)
(including age > 65 years and/or underlying end-organ dysfunction)
Pneumonia• Lopinavir-ritonavir (400 mg/100 mg bid) + Chloroquine (500 mg bid) or HCQ (200 mg bid) for 5–20 days)
BCRSS* score ≥ 2, consider adding:
- Dexamethasone 20 mg/day for 5 days, then 10 mg/d for 10 days (discuss with intensivist)
and/or
- Tocolizumab
Nil
Severe• Convalescent plasma
• Tocolizumab (extensive lung disease, increased IL-6; prohibited in active tuberculosis)(IV, 4–8 mg/kg, maximum 2 cumulative doses)
• Glucocorticoids (not exceeding equivalent of methylprednisolone 1–2 mg/(kg·d), for 3–5 days)
• Xuebijing (TCM)(100 ml bid)
• Probiotics
Nil mentioned• Chloroquine (600 mg loading dose, 300 mg 12 h later, followed by 300 mg bid on days 2–5
or
• HCQ (400 mg bid loading dose, then 200 mg bid on days 2–5)
Consider switching or adding remdesivir if insufficient response or clinical deterioration
• Prophylactic LMWH
• Start HCQ or chloroquine (above dose)
• Consider lopinavir-ritonavir (400 mg/100 mg bd for 14 days) only if HCQ/ chloroquine is contraindicated and if it can be administrated with 12 days of symptom onset
Critical• Remdesivir (IV 200 mg loading dose on day 1, maintenance dose 200 mg/d from day 2–10) + chloroquine/HCQ (above dose)
or
• Lopinavir-ritonavir + chloroquine/HCQ (above dose)
ARDS:
• Dexamethasone 20 mg/d for 5 days, then 10 mg/d for 5 days; to initiate within 24 h of ARDS diagnosis (discuss with intensivist)
and/or
• Tocilizumab
• Chloroquine/ HCQ + remdesivir (200 mg loading dose on day 1, then 100 mg daily for days 2–9)
or
• Remdesivir alone
• Remdesivir (200 mg loading dose within 30 min, followed by 100 mg daily for 2–10 days)
• Consider HCQ/ chloroquine if remdesivir unavailable
• IL-6 inhibitors should only be used in clinical trials
  1. BCRSS* Brescia-COVID Respiratory Severity Scale, based on 4 criteria: patient wheezing or unable to speak in full sentences while at rest/with minimal effort; respiratory rate > 22, PaO2 < 65 mmHg or SpO2 < 90%; worsening repeat chest X-ray (not externally validated), WHO World Health Organization, NHC National Health Commission, SIMIT Società Italiana di Malattie Infettive e Tropicali, SWAB Stichting Werkgroep Antibiotica Beleid, HCQ Hydroxychloroquine, bid Twice a day, tid Three times a day, RR Respiratory rate, SpO2 Peripheral oxygen saturation, PaO2 Partial pressure of arterial oxygen, FiO2 Fraction of inspired oxygen, TCM Traditional Chinese medicine, IV Intravenous, LMWH Low molecular weight heparin, ARDS Acute respiratory distress syndrome, DVT Deep venous thrombosis, ECMO Extracorporeal membrane oxygenation