COVID-19 treatment: monoclonal antibodies

Protocols typically combine multiple treatments. No single treatment is guaranteed to be effective and safe for a specific individual. Leading evidence-based protocols combine multiple treatments.

Complementary and synergistic actions. There are many complementary mechanisms of action across treatments, and studies show complementary and synergistic effects with polytherapy121-137. For example, Jitobaom et al.122 showed >10x reduction in IC₅₀ with ivermectin and niclosamide, an RCT by Said et al.129 showed the combination of nigella sativa and vitamin D was more effective than either alone, and an RCT by Wannigama et al.138 showed improved results with fluvoxamine combined with bromhexine, cyproheptadine, or niclosamide, compared to fluvoxamine alone. Treatment efficacy may vary significantly across SARS-CoV-2 variants. For example new variants may gain resistance to targeted treatments139-145, and the role of TMPRSS2 for cell entry differs across variants146. The efficacy of specific treatments varies depending on cell type147 due to differences in viral receptor expression, drug distribution and metabolism, cell-specific mechanisms, and the relevance of drug targets to specific cells. Efficacy may also vary based on genetic variants148-151. Variable efficacy across SARS-CoV-2 variants, cell types, different 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. 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.

SARS-CoV-2 evolution and the risk of escape mutants suggests treatments with broader mechanisms of action and polytherapy. SARS-CoV-2 can rapidly acquire mutations altering infectivity, disease severity, and drug resistance even without selective pressure152. Antigenic drift can undermine more variant-specific treatments like monoclonal antibodies and more specific antivirals. Treatment with targeted antivirals may select for escape mutations153. Less variant specific treatments and polytherapy targeting multiple viral and host proteins may be more effective.