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Abstract

Background

Monoclonal antibodies (mAbs) and antiviral drugs have emerged as additional tools for treatment of COVID-19.

Aim

We aimed to review data on susceptibility of 14 SARS-CoV-2 variants to mAbs and antiviral drugs authorised in the European Union/European Economic Area (EU/EEA) countries.

Methods

We constructed a literature review compiling 298 publications from four databases: PubMed, Science Direct, LitCovid and BioRxiv/MedRxiv preprint servers. We included publications on nirmatrelvir and ritonavir, remdesivir and tixagevimab and cilgavimab, regdanvimab, casirivimab and imdevimab, and sotrovimab approved by the European Medicines Agency (EMA) by 1 October 2024.

Results

The mutations identified in the open reading frame (ORF)1ab, specifically nsp5:H172Y, nsp5:H172Y and Q189E, nsp5:L50F and E166V and nsp5:L50F, E166A and L167V, led to a decrease in susceptibility to nirmatrelvir and ritonavir, ranging from moderate (25-99) to high reductions (> 100). Casirivimab and imdevimab exhibited highly reduced neutralisation capacity across all Omicron sub-lineages. Sub-lineages BA.1, BA.2 and BA.5 had decreased susceptibility to regdanvimab, while sotrovimab showed decreased efficacy for BA.2, BA.4, BQ.1.1 and BA.2.86. Tixagevimab and cilgavimab exhibited highly reduced neutralisation activity against BQ.1, BQ.1.1, XBB, XBB.1.5 and BA.2.86 sub-lineages.

Conclusions

The emergence of new variants, some with altered antigenic characteristics, may lead to resistance against mAbs and/or antiviral drugs and evasion of immunity induced naturally or by vaccination. This summary of mutations, combination of mutations and SARS-CoV-2 variants linked to reduced susceptibility to mAbs and antiviral drugs, should aid the selection of appropriate treatment strategies and/or phasing out therapies that have lost their effectiveness.

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2025-03-13
2025-03-17
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Impact of SARS-CoV-2 variant mutations on susceptibility to monoclonal antibodies and antiviral drugs: a non-systematic review, April 2022 to October 2024
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Maja+Vukovikj&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Vukovikj Maja</a>, <a href="/search?value1=Angeliki+Melidou&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Melidou Angeliki</a>, <a href="/search?value1=Priyanka+Nannapaneni&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Nannapaneni Priyanka</a>, <a href="/search?value1=Tanja+Normark&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Normark Tanja</a>, <a href="/search?value1=Annette+Kraus&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Kraus Annette</a>, <a href="/search?value1=Eeva+K+Broberg&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Broberg Eeva K</a></span>. Impact of SARS-CoV-2 variant mutations on susceptibility to monoclonal antibodies and antiviral drugs: a non-systematic review, April 2022 to October 2024. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(10):pii=2400252. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.10.2400252" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.10.2400252</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 25 Apr 2024;&nbsp;&nbsp; <span class="generated">Accepted</span>: 10 Dec 2024 </span> </p>
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