TOPLINE:

Both intravenous (IV) and intramuscular (IM) administration of the monoclonal antibody tixagevimab/cilgavimab rapidly eliminated culturable SARS-CoV-2, with both routes yielding minimal emergence of resistance-associated mutations.

METHODOLOGY:

• In a substudy of a trial, researchers compared IM and IV administration of the monoclonal antibody tixagevimab/cilgavimab in nonhospitalized patients with mild-to-moderate COVID, assessing viral culture conversion and the emergence of resistance.
• A total of 313 participants (enrolled within 10 days of symptom onset) were randomly assigned to receive IM tixagevimab/cilgavimab (n = 98; median age, 40 years; 51% women), IV tixagevimab/cilgavimab (n = 54; median age, 43 years; 61% women), or matching placebo.
• Viral cultures were obtained from anterior nasal and nasopharyngeal swabs on specified days to measure viral RNA levels and sequence the SARS-CoV-2 spike gene for detection of mutations associated with emergent resistance.

TAKEAWAY:

• On day 1 post-infusion, SARS-CoV-2 RNA levels were similar across the IM, IV, and placebo arms; however, culture positivity was lower among participants receiving monoclonal antibody than among those receiving placebo (6.3% vs 62%; P = .007).
• By day 2 post-infusion, 50% of the participants receiving placebo showed culture positivity, whereas none of the participants receiving monoclonal antibody showed culture positivity.
• The median time to culture conversion was ≤ 1 day among participants receiving monoclonal antibody compared with 2.5 days among those receiving placebo.
• Treatment-emergent resistance mutations were rare; they occurred at similar rates in the IM and placebo arms (1.0% and 1.8%, respectively) and were absent in the IV arm and its corresponding placebo arm (0% in both arms).

IN PRACTICE:

“The comparable virologic effects of IM and IV administration are particularly relevant for clinical and public health planning,” the authors wrote. 

“IM delivery offers a practical alternative that can be more easily implemented in outpatient or mass vaccination-style setting,” they added.

SOURCE:

The study was led by Rinki Deo, PhD, Brigham and Women’s Hospital, Harvard Medical School, Boston. It was published online on September 8, 2025, in Open Forum Infectious Diseases. 

LIMITATIONS:

The study was limited by the small sample size in the viral culture subset and its focus on pre-Omicron variants.

DISCLOSURES:

The study was supported by the National Institutes of Health. Some authors served as consultants and received research support from various sources. Additionally, some authors were employees of Vaccines and Immune Therapies at AstraZeneca in the US and UK.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.