COVID-19 treatment: monoclonal antibodies

• Monoclonal antibodies are effective for matching variants, but were rarely used

@CovidAnalysis, November 21, 2025
c19early.org
Efficacy confidence - mAbs
Casirivimab/imdevimabp=0.0001
Bamlanivimab/etesevimabp=0.0005
Regdanvimabp=0.0005
Sotrovimabp=0.0005
Tixagevimab/cilgavimabp=0.007
mAbs show high variant dependence—may not be effective for recent variants.

P-values indicate the confidence that studies show a significant effect. p=0.05 is the typical threshold for significance, with lower values indicating higher confidence. See the individual analyses for details of efficacy for specific outcomes and conditions.
Monoclonal antibodies (mAbs) Many mAbs have shown efficacy, including casirivimab/imdevimab, bamlanivimab/etesevimab, tixagevimab/cilgavimab, sotrovimab, and regdanvimab1-118, however they are highly variant dependent and may have limited or no efficacy with more recent variants. They also require intravenous, subcutaneous, or intramuscular administration, limiting easy and immediate access, have been linked to the creation of new variants119-121, and may increase risk with the potential for emergence of resistant mutations during treatment122,123. Although highly effective for the appropriate variants, mAbs were rarely used124.
Protocols combine multiple treatments No single treatment is guaranteed to be effective and safe for a specific individual. Leading evidence-based protocols combine multiple treatments.
c19early.org
Combined treatments increase efficacy
Monotherapy33% [30‑36%]
Polytherapy68% [57‑77%]
 Meta analysis of early treatment studies.
Complementary/synergistic actions, viral evolution, escape risk suggest polytherapy There are many complementary mechanisms of action, and studies show complementary and synergistic effects with polytherapy128-144. For example, Jitobaom et al.129 shows >10x reduction in IC50 with ivermectin and niclosamide, an RCT by Said et al.136 showed the combination of nigella sativa and vitamin D was more effective than either alone, and an RCT by Wannigama et al.145 showed improved results with fluvoxamine combined with additional treatments, compared to fluvoxamine alone.
SARS-CoV-2 can rapidly acquire mutations altering infectivity, disease severity, and drug resistance even without selective pressure146-153. Antigenic drift can undermine more variant-specific treatments like monoclonal antibodies and more specific antivirals. Treatment with targeted antivirals may select for escape mutations154. The efficacy of treatments varies depending on cell type155 due to differences in viral receptor expression, drug distribution and metabolism, and cell-specific mechanisms. Efficacy may also vary based on genetic variants156-166.
Variable efficacy across variants, cell types, tissues, and host genetics, along with the complementary and synergistic actions of different treatments, all point to greater efficacy with polytherapy. In many studies, the standard of care given to all patients includes other treatments—efficacy seen in these trials may rely in part on synergistic effects. Less variant specific treatments and polytherapy targeting multiple viral and host proteins may be more effective. Meta analysis of all early treatment trials shows 68% [57‑77%] lower risk for studies using combined treatments, compared to 33% [30‑36%] for single treatments.
 
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