Controversies’ clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages

Table 4 Treatment recommendations for viral hemorrhagic fevers and coronavirus outbreaks

Ref.	Number of patients/RBV commencement after symptom onset in d	Treatment protocol/dosing regimens	Outcomes	Authors’ conclusions	Comments
Viral hemorrhagic fevers
Borio et al[123], United States	Recommendations for viral hemorrhagic fevers	Intravenous: ld of 30 mg/kg (max of 2 g) once, followed by 16 mg/kg (max of 1 g per dose), qid × 4 d, followed by 8 mg/kg (max of 500 mg per dose) tid × 6 d	Peros: Ld 2000 mg → 1200 mg/d in two divided doses (if weight > 75 kg) or 1000 mg/d in two doses (400-600 mg) if weight ≤ 75 kg for 10 d	RBV is the only potentially effective drug available for selected hemorrhagic fevers	There seems to be a discrepancy between the iv and the oral posology
SARS-CoV
Koren et al[91], Canada	Recommendations by the Canadian Society for Clinical Pharmacology	Recommended RBV dosage adjusted to Crcl: If Crcl > 60 mL/min → 400 mg tid iv × 3 d, then 1200 mg bid × 7 d	Adverse events: Dose-dependent anemia; electrolyte disturbances (hypocalcemia, hypomagnesemia) CNS effects; teratogenic potential	Until more information becomes available, RBV will continue to be recommended at least in a subset of sicker patients	Deals mostly with RBV adverse-effects
MERS-CoV
Chong et al[158], Korea	Antivirals should be considered as soon as possible after diagnosis	High-dose: 2.0 g po Ld → 1.2 g tid po × 4 d → 600 mg tid po × 4-6 d (adjusted to Crcl). Intermediate-dose: 2.0 g po. Ld → 10 mg/kg po tid × 10 d. IFN-α2a 180 μg/wk sc × 2 wk. Lop/r 400/100 mg po bid × 10 d	No data available. Side-effects: RBV → hemolytic anemia. Peg-IFN → myeloid dysfunction	The Guidelines focus on antiviral drugs to achieve effective management of MERS treatment	OK
SARS-CoV-2
National Health Commission of the People’s Republic of China: the COVID-19 Diagnosis and Treatment Guide 7th Edition[188], China	RBV 500 mg iv bid or tid × 10 d Use in combination with Lop/r or IFNs	IFΝ-α 5 MU nebulization bid. Lop/r 400/100 mg bid 10 d. Chloroquine 500 mg po bid × 7 d. Umifenovir 200 mg po tid × 10 d	Lp/r: Monitor closely for nausea/vomiting. Chloroquine: Avoid in cardiovascular disease. Concurrent use of three or more antiviral agents is not recommended		OK

bid: Bis in die; CNS: Central nervous system; COVID-19: Coronavirus disease 2019; Crcl: Creatinine clearance; ENT: Equilibrative nucleoside transport; GTP: Guanosine triphosphate; IFN: Interferon; iv: Intravenous; ld: Loading dose; Lop/r: Lopinavir/ritonavir; MERS: Middle East respiratory syndrome; po: Per os; Peg: Pegylated; RBV: Ribavirin; RdRp: RNA-dependent RNA polymerase; sc: Subcutaneous; tid: Ter in die.