Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2.
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ABSTRACT:
SUBMITTER: Martin-Blondel G
PROVIDER: S-EPMC9254651 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesOur aim was to compare the clinical and virological outcomes in Omicron BA.1- and BA.2-infected patients who received sotrovimab with those in patients who received nirmatrelvir for the prevention of severe COVID-19.MethodsIn this multi-centric, prospective ANRS 0003S CoCoPrev cohort study, patients at a high risk of progression of mild-to-moderate BA.1 or BA.2 COVID-19 who received sotrovimab or nirmatrelvir were included. The proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR conversion, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multi-variable Cox proportional hazard model was used to determine the time to negative PCR conversion and a mixed-effect model for the dynamics of viral decay.ResultsAmongst 255 included patients, 199 (80%) received ≥3 vaccine doses, 195 (76%) received sotrovimab, and 60 (24%) received nirmatrelvir. On day 28, new COVID-19-related hospitalization occurred in 4 of 193 (2%; 95% CI, 1-5%) sotrovimab-treated patients and 0 of 55 nirmatrelvir-treated patients (p 0.24). One out of the 55 nirmatrelvir-treated patients died (2%; 95% CI, 0-10%). The median time to negative PCR conversion was 11.5 days (95% CI, 10.5-13) in the sotrovimab-treated patients vs. 4 days (95% CI, 4-9) in the nirmatrelvir-treated patients (p < 0.001). Viral decay was faster in the patients who received nirmatrelvir (p < 0.001). In the multi-variable analysis, nirmatrelvir and nasopharyngeal PCR cycle threshold values were independently associated with faster conversion to negative PCR (hazard ratio, 2.35; 95% CI, 1.56-3.56; p < 0.0001 and hazard ratio, 1.05; 95% CI, 1.01-1.08; p 0.01, respectively).ConclusionsEarly administration of nirmatrelvir in high-risk patients compared with that of sotrovimab was associated with faster viral clearance. This may participate to decrease transmission and prevent viral resistance.
| S-EPMC9794519 | biostudies-literature
Project description:BackgroundUnderstanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants.MethodsA total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status.ResultsThe neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients.ConclusionsVaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.
| S-EPMC10974415 | biostudies-literature
Project description:We completed a real-world analysis of 498 consecutive high-risk nonimmunocompromised and immunocompromised patients who received sotrovimab during the B.1.1.529 surge. Emergency department visits/hospitalizations and 30-day all-cause mortality between the 2 groups were similar. When administered early, sotrovimab is effective at preventing coronavirus disease 2019 progression in immunocompromised and nonimmunocompromised patients.
| S-EPMC9214182 | biostudies-literature
Project description: Not available
| S-EPMC9344387 | biostudies-literature
Project description:BackgroundThis study aimed to investigate the deaths due to coronavirus disease 2019 (COVID-19) reinfection and related risk factors.MethodsNational cohort data were collected for a six-month period when omicron BA.1/BA.2 variant was dominant in South Korea.ResultsThe long-term care facility residents (adjusted odds ratio, 3.11; 95% confidence interval [CI], 2.98-3.25) had significantly higher risk of reinfection than the general population. The risk of reinfection was significantly lower for persons with 2 or more vaccine doses compared to the unvaccinated. The risk of death was significantly higher in the reinfection group than in the primary infection group for persons in the 60-74 years age group (adjusted relative risk [aRR], 1.62; 95% CI, 1.19-2.20), and immunocompromised group (aRR, 4.56; 95% CI, 2.34-8.90).ConclusionIn these data, vaccination history was significantly related to reduced COVID-19 reinfection and severe progression, and scheduled vaccinations were important even with a history of infection.
| S-EPMC10462479 | biostudies-literature
Project description:BackgroundTimely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.MethodsWith the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.FindingsA total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n = 5704) and sotrovimab (n = 3322) were included in the main analysis. The mean age was 52.7 (SD = 14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR = 0.89, 95% CI: 0.48-1.63; P = 0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR = 0.82, 95% CI: 0.45-1.52; P = 0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR = 0.45, 95% CI: 0.22-0.94; P = 0.033).InterpretationIn routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.FundingUK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.
| S-EPMC10624988 | biostudies-literature
Project description:BackgroundRemdesivir and sotrovimab both have clinical trial data in the outpatient setting demonstrating reduction in the risk of hospitalizations and emergency department (ED) visits related to COVID-19.ObjectivesTo evaluate the effectiveness of remdesivir in comparison with sotrovimab and matched high-risk control patients in preventing COVID-19-related hospitalizations and ED visits during the Omicron B.1.1.529 surge.Patients and methodsThis retrospective cohort study included outpatients positive for SARS-CoV-2, with non-severe symptoms for ≤7 days and deemed high-risk for severe COVID-19 by an internal scoring matrix. Patients who received remdesivir or sotrovimab from 27/12/2021 to 04/02/2022 were included (n = 82 and n = 88, respectively). These were compared with a control cohort of high-risk COVID-19 outpatients who did not receive therapy (n = 90). The primary outcome was a composite of 29 day COVID-19-related hospitalizations and/or ED visits. Pre-specified secondary outcomes included components of the primary endpoint, 29 day all-cause mortality and serious adverse drug events.ResultsPatients treated with remdesivir were significantly less likely to be hospitalized or visit the ED within 29 days from symptom onset (11% versus 23.3%; OR = 0.41, 95% CI = 0.17-0.95). Patients receiving sotrovimab were also less likely to be hospitalized or visit the ED (8% versus 23.3%; OR = 0.28, 95% CI = 0.11-0.71). There was no difference in the incidence of hospitalizations/ED visits between sotrovimab and remdesivir.ConclusionsOur highest-risk outpatients with Omicron-related COVID-19 who received early sotrovimab or remdesivir had significantly lower likelihoods of a hospitalization and/or ED visit.
| S-EPMC9384598 | biostudies-literature
Project description:BackgroundMany previous studies have reported that COVID-19 vaccine effectiveness decreased over time and declined with newly emerging variants. However, there are few such studies in Japan. Using data from a community-based retrospective study, we aimed to assess the association between vaccination status and severe COVID-19 outcomes caused by the Omicron variant, considering the length of time since the last vaccination dose.MethodsWe included all persons aged ≥12 diagnosed with COVID-19 by a doctor and notified to the Chuwa Public Health Center of Nara Prefectural Government during the Omicron BA.1/BA.2 and BA.5-predominant periods in Japan (January 1 to September 25, 2022). The outcome variable was severe health consequences (SHC) (i.e., COVID-19-related hospitalization or death). The explanatory variable was vaccination status of the individuals (i.e., the number of vaccinations and length of time since last dose). Covariates included gender, age, risk factors for aggravation, and the number of hospital beds per population. Using the generalized estimating equations of the multivariable Poisson regression models, we estimated the cumulative incidence ratio (CIR) and 95% confidence interval (CI) for SHC, with stratified analyses by period (BA.1/BA.2 or BA.5) and age (65 and older or 12-64 years).ResultsOf the 69,827 participants, 2,224 (3.2%) had SHC, 12,154 (17.4%) were unvaccinated, and 29,032 (41.6%) received ≥3 vaccine doses. Regardless of period or age, there was a significant dose-response relationship in which adjusted CIR for SHC decreased with an increased number of vaccinations and a longer time since the last vaccination. On the one hand, in the BA.5 period, those with ≥175 days after the third dose had no significant difference in people aged 65 and older (CIR 0.77; 95% CI, 0.53-1.12), but significantly lower CIR for SHC in people aged 12-64 (CIR 0.47; 95% CI, 0.26-0.84), compared with those with ≥14 days after the second dose.ConclusionA higher number of vaccinations were associated with lower risk of SHC against both BA.1/BA.2 and BA.5 sublineages. Our findings suggest that increasing the number of doses of COVID-19 vaccine can prevent severe COVID-19 outcomes, and that a biannual vaccination is recommended for older people.
| S-EPMC10287986 | biostudies-literature
Project description: Not available
| S-EPMC10675676 | biostudies-literature
Project description:SARS-CoV-2 vaccines, administered to billions of people worldwide, mitigate the effects of the COVID-19 pandemic, however little is known about the molecular basis of antibody cross-protection to emerging variants, such as Omicron BA.1, its sublineage BA.2, and other coronaviruses. To answer this question, 276 neutralizing monoclonal antibodies (nAbs), previously isolated from seronegative and seropositive donors vaccinated with BNT162b2 mRNA vaccine, were tested for neutralization against the Omicron BA.1 and BA.2 variants, and SARS-CoV-1 virus. Only 14.2, 19.9 and 4.0% of tested antibodies neutralize BA.1, BA.2, and SARS-CoV-1 respectively. These nAbs recognize mainly the SARS-CoV-2 receptor binding domain (RBD) and target Class 3 and Class 4 epitope regions on the SARS-CoV-2 spike protein. Interestingly, around 50% of BA.2 nAbs did not neutralize BA.1 and among these, several targeted the NTD. Cross-protective antibodies derive from a variety of germlines, the most frequents of which were the IGHV1-58;IGHJ3-1, IGHV2-5;IGHJ4-1 and IGHV1-69;IGHV4-1. Only 15.6, 20.3 and 7.8% of predominant gene-derived nAbs elicited against the original Wuhan virus cross-neutralize Omicron BA.1, BA.2 and SARS-CoV-1 respectively. Our data provide evidence, at molecular level, of the presence of cross-neutralizing antibodies induced by vaccination and map conserved epitopes on the S protein that can inform vaccine design.
| S-EPMC9189263 | biostudies-literature