Quality of evidence: C
Controversial treatments: an updated understanding of the Coronavirus Disease 2019
Authors: Zhang C et al
Journal: Journal of Medical Virology
Objectives: Adress the controversies around experimental treatments
Strength of evidence: Low (limited sources and no methodology reported)
Methods/publication type:
Review of the literature
Reports mechanism of action, advantages and side effects of the treatments reported for COVID-19 as of 26 march 2020
Highlights :
Overall: antiviral therapy is most effective in moderate cases while supporting vital functions (artificial organs) seem more adequate for severe cases
Remdesivir (antiviral): Quality of evidence = C
Blocks the action of the RNA-dependent RNA-RNA polymerase complex (substrate for RdRp or compete with ATP)
Showed efficacy in SARS and MERS (in vitro and in vivo animal studies)
1 COVID-19 patient (case-report) treated with intravenous Remdesivir without adverse effects on the 7th day of hospitalization, the symptoms regressed from the 8th day
One Chinese clinical trial in phase III: 100mg (200mg the first day) vs placebo.
Side effects yet to be unveiled
Ribavirin (antiviral): quality of evidence = C+
Broad-spectrum
Phosphorylated in infected cells and blocks viral transcription
FDA approved for respiratory syncytial virus
Controversial on SARS (4 studies found an antiviral effect, 2 found none, no evidence of clinical value)
Data missing on COVID-19
Significant side effects: hemolytic anemia
Chloroquine and derivatives (antimalarial): quality of evidence C-
Only studies in vitro/animal model reviewed
Prevent endosomal pH lowering necessary for virus endosome escape
Chloroquine and its derivatives inhibit viral replication in vitro
Might interfere with ACE2 glycosylation (target of SARS-COV-2)
Processed by the liver, long half-life (2.5 to 10 days) = accumulation + toxicity in patients with liver failure (e.g. certain COVID-19 patients)
Lethal dose 2 to 4 g
side effects: cardiotoxicity, irreversible retinopathy, gastrointestinal dysregulation, psychological side-effects
NB: new studies on patients not included. However, as these new studies are low-quality evidence (C to D), the overall appreciation of the evidence on this drug does not change.
Corticosteroids (anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive): quality of evidence: C
Previously used in SARS and MERS
No evidence of antiviral effects against SARS-CoV-2 in vitro
Use supported for patients with pulmonary edema and hyaline membrane formation in other diseases
Side effects: avascular necrosis, psychosis, diabetes
Not recommended (OMS + 1 publication) for COVID-19 unless there are underlying conditions
Artificial liver replacement: quality of evidence: C
Three types of tools: non-organic, organic and hybrid
Helps the liver by removing drugs/inflammatory factors (cytokine storm), give time for liver cell regeneration
Previously used in ARDS patients
Some results reported in Wuhan for Covid-19 (low quality)
Risky in case of bleeding, DIC, hypotension, secondary infections, reaction allergic, hydro-electric imbalance
Extracorporeal membrane oxygenation (ECMO), quality of evidence: C+
Temporarily supports breathing and prevent lung damage due to high volumes and pressures
3 studies found it improved ventilation and oxygenation in patients with ARDS (H7N9/H1N1
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