Table 3.

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

Severity of COVID-19 (WHO classification)	NHC (China)	SIMIT Lombardy section (Italy)	SWAB (Netherlands)	Sciensano (Belgium)
Mild	Symptomatic 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 treatment	Symptomatic 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

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