Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern.

Background: Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods: The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results: Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01). Conclusions: Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn. Funding: This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number: NCT05205759.

Epidemiological and Clinical Features of SARS-CoV-2 Variants Circulating between April-December 2021 in Italy.

SARS-CoV-2 is constantly evolving, leading to new variants. We analysed data from 4400 SARS-CoV-2-positive samples in order to pursue epidemiological variant surveillance and to evaluate their impact on public health in Italy in the period of April-December 2021. The main circulating strain (76.2%) was the Delta variant, followed by the Alpha (13.3%), the Omicron (5.3%), and the Gamma variants (2.9%). The B.1.1 lineages, Eta, Beta, Iota, Mu, and Kappa variants, represented around 1% of cases. There were 48.2% of subjects who had not been vaccinated, and they had a lower median age compared to the vaccinated subjects (47 vs. 61 years). An increasing number of infections in the vaccinated subjects were observed over time, with the highest proportion in November (85.2%). The variants correlated with clinical status; the largest proportion of symptomatic patients (59.6%) was observed with the Delta variant, while subjects harbouring the Gamma variant showed the highest proportion of asymptomatic infection (21.6%), albeit also deaths (5.4%). The Omicron variant was only found in the vaccinated subjects, of which 47% had been hospitalised. The diffusivity and pathogenicity associated with the different SARS-CoV-2 variants are likely to have relevant public health implications, both at the national and international levels. Our study provides data on the rapid changes in the epidemiological landscape of the SARS-CoV-2 variants in Italy.

Clinical characteristics and laboratory biomarkers changes in COVID-19 patients requiring or not intensive or sub-intensive care: a comparative study.

BACKGROUND: Identifying risk factors for severe novel-coronavirus disease (COVID-19) is useful to ascertain which patients may benefit from advanced supportive care. The study offers a description of COVID-19 patients, admitted to a general ward for a non-critical clinical picture, with the aim to analyse the differences between those transferred to the intensive (ICU) and/or sub-intensive care (SICU) units and those who were not. METHODS: This observational retrospective study includes all COVID-19 patients admitted to the Infectious Diseases Unit. Clinical, laboratory, radiological and treatment data were collected. The primary outcome was a composite of need of transfer to the ICU and/or SICU during the hospitalization. Patients who did not require to be transferred are defined as Group 1; patients who were transferred to the ICU and/or SICU are defined as Group 2. Demographic, clinical characteristics and laboratory findings at the 1st, 3rd and last measurements were compared between the two groups. RESULTS: 303 were included. The median age was 62 years. 69 patients (22.8%) met the primary outcome and were defined as Group 2. The overall fatality rate was 6.8%. Group 2 patients were predominantly male (76.8% vs. 55.1%, p < 0.01), had a higher fatality rate (14.5% vs. 3.8%, p < 0,01), had more hypertension (72.4% vs. 44%, p < 0,01) and diabetes (31.9% vs. 21%, p = 0.04) and were more likely to present dry cough (49.3% vs. 25.2%, p < 0.01). Overall, chest X-ray at admission showed findings suggestive of pneumonia in 63.2%, and Group 2 were more likely to develop pathological findings during the hospitalization (72.7% vs. 17.2%, p = 0.01). At admission, Group 2 presented significantly higher neutrophil count, aspartate-transaminase and C-Reactive-Protein. At the 3rd measurement, Group 2 presented persistently higher neutrophil count, hepatic inflammation markers and C-Reactive-Protein. Group 1 presented a shorter duration from admission to negativization of follow-up swabs (20 vs. 35 days, p < 0.01). CONCLUSIONS: The presence of comorbidities and the persistent observation of abnormal laboratory findings should be regarded as predisposing factors for clinical worsening.

An Integrated Strategy for the Prevention of SARS-CoV-2 Infection in Healthcare Workers: A Prospective Observational Study.

BACKGROUND: Since the beginning of SARS-CoV-2 outbreak, a large number of infections have been reported among healthcare workers (HCWs). The aim of this study was to investigate the occurrence of SARS-CoV-2 infection among HCWs involved in the first management of infected patients and to describe the measures adopted to prevent the transmission in the hospital. METHODS: This prospective observational study was conducted between February 21 and April 16, 2020, in the Padua University Hospital (north-east Italy). The infection control policy adopted consisted of the following: the creation of the "Advanced Triage" area for the evaluation of SARS-CoV-2 cases, and the implementation of an integrated infection control surveillance system directed to all the healthcare personnel involved in the Advance Triage area. HCWs were regularly tested with nasopharyngeal swabs for SARS-CoV-2; body temperature and suggestive symptoms were evaluated at each duty. Demographic and clinical data of both patients and HCWs were collected and analyzed; HCWs' personal protective equipment (PPE) consumption was also recorded. The efficiency of the control strategy among HCWs was evaluated identifying symptomatic infection (primary endpoint) and asymptomatic infection (secondary endpoint) with confirmed detection of SARS-CoV-2. RESULTS: 7595 patients were evaluated in the Advanced Triage area: 5.2% resulted positive and 72.4% was symptomatic. The HCW team was composed of 60 members. A total of 361 nasopharyngeal swabs were performed on HCWs. All the swabs resulted negative and none of the HCWs reached the primary or the secondary endpoint. CONCLUSIONS: An integrated hospital infection control strategy, consisting of dedicated areas for infected patients, strict measures for PPE use and mass surveillance, is successful to prevent infection among HCWs.