In a recent study posted to the medRxiv* preprint server, researchers depicted the efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) against the SARS-CoV-2 Omicron variant.
The coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has spread globally and created a significant threat to healthcare systems. Although the mass SARS-CoV-2 vaccination rollouts notably lowered the COVID-19-linked healthcare burden, the vaccination rates varied substantially over nations, and they demonstrated minimized effect against novel viral variants of concern (VOCs).
Therapeutic agents targeting SARS-CoV-2 have been developed to slow COVID-19 progression, particularly in at-risk patients (older and those with comorbidities). The SARS-CoV-2 spike (S) protein, which enables the viral host entrance, is targeted by the COVID-19 neutralizing mAbs. The activity of mAbs addressing SARS-CoV-2 differs depending on the VOC, according to recent in vitro findings. However, no existing studies examined the clinical effectiveness of various mAbs towards the SARS-CoV-2 Omicron VOC.
About the study
The present work reported the findings of the MANTICO study, a randomized controlled non-inferiority trial assessing the clinical effectiveness of commonly used mAbs, such as sotrovimab, etesevimab/bamlanivimab, and imdevimab/casirivimab, in outpatients aged ≥50 years experiencing early mild/moderate SARS-CoV-2 infection. Patient enrollment for MANTICO research began in December 2021. However, it was halted because in vitro data showed that two therapies under consideration (etesevimab/bamlanivimab and imdevimab/casirivimab) were ineffective against the novel SARS-CoV-2 Omicron VOC.
Subsequently, the study was limited to 319 randomized COVID-19 patients recruited up to the point of futility interruption and was conducted based on the SARS-CoV-2 VOC (Omicron and Delta).
The main outcome was the progression of SARS-CoV-2 infection, such as COVID-19-linked hospitalization, mortality, or need for supplemental oxygen therapy for two weeks. Secondary outcomes consisted of the duration for COVID-19 symptom resolution, estimated by the product-limit approach. The connection of the symptom resolution time with predictors was assessed using the Cox proportional hazard model and the Kaplan-Meier estimator. Besides, the survival functions were compared using the log-rank test.
The study results demonstrated that the investigation included 319 COVID-19 patients. Further, the SARS-CoV-2 VOC data was available for 311 subjects, illustrating that 170 patients had Omicron infection and 141 were infected with Delta.
While COVID-19-associated symptoms like ageusia/anosmia, vomiting/nausea, and high temperature/feverish feeling were common in Delta-infected patients, people infected with Omicron more frequently experienced sore throat during enrollment. Patients infected with Omicron had substantially higher rates of anti-COVID-19 antibody positivity and completed the main SARS-CoV-2 vaccine regimen within 180 days of enrolling or booster vaccination. Moreover, the team found that in both SARS-CoV-2 VOCs, no predictors correlated with the symptom resolution time.
The most commonly detected Delta lineages were AY.4, AY.43, and AY.122. Additionally, among the 141 Delta-infected patients, 77 were men, the median age was 65.7 years, minimum of one comorbidity was present in 115, 74 had serum antibody positivity at the time of recruitment, and 23 had completed the primary SARS-CoV-2 vaccination series within 180 days of enrollment or booster vaccination.
The authors noted that no COVID-19 progression was documented among 141 individuals infected with the SARS-CoV-2 Delta VOC, and the time for resolution of symptoms did not vary substantially among mAbs treatment groups. The median symptom resolution time was a week for the etesevimab/bamlanivimab group and 10 days for both the sotrovimab and imdevimab/casirivimab cohorts. It did not drastically vary between overall treatment groups and every inter-group comparison, such as etesevimab/bamlanivimab with imdevimab/casirivimab.
Among 170 individuals infected with the Omicron VOC, COVID-19 progression resulting in hospitalization was documented in two patients belonging to the etesevimab/bamlanivimab group. However, no illness progression was documented in the sotrovimab and imdevimab/casirivimab groups.
The median symptom resolution time was 12 days for both etesevimab/bamlanivimab and imdevimab/casirivimab cohorts. Further, it was five days shorter in the sotrovimab group than in the etesevimab/bamlanivimab and imdevimab/casirivimab arms for the Omicron BA.1.1- and BA.1-infected individuals. This advantage was seen in all Omicron subgroups, irrespective of SARS-CoV-2 vaccination or serology status, corroborating preliminary in vitro findings of mAb efficacy towards Omicron BA.1.1 and BA.1 subvariants.
The authors stated that the MANTICO research was the first to show that etesevimab/bamlanivimab, sotrovimab, and imdevimab/casirivimab were effective against the SARS-CoV-2 Omicron VOC.
The study findings backed the previous in vitro evidence showing sotrovimab to be better than imdevimab/casirivimab and etesivamab/bamlanivimab in lowering the recovery time in individuals infected with the Omicron BA.1.1 and BA.1 sublineages. Yet, no variation was seen in Delta infections.
In the Omicron-infected population, imdevimab/casirivimab appeared to have a role in averting severe SARS-CoV-2 infections. Besides, the researchers mentioned that adaptive clinical studies comparing anti-SARS-CoV-2 therapies by VOC were urgently needed to inform management recommendations for early COVID-19.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Fulvia Mazzaferri, et al. (2022). Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron Variant of Concern. medRxiv. doi: https://doi.org/10.1101/2022.05.06.2227461 https://www.medrxiv.org/content/10.1101/2022.05.06.22274613v1