Medical Bulletin 16/October/2023

SARS-CoV-2 Variants of Concern in Children and Adolescents: Insights from a Comprehensive Study

In the ongoing fight against the COVID-19 pandemic, understanding the impact of SARS-CoV-2 variants of concern (VOCs) is crucial, particularly in the context of children and adolescents. A recent study sought to answer five pivotal questions, shedding light on how these variants affect young individuals.

1. Symptoms and Severity: The study reveals that, in most cases, children with any VOC infection experienced mild symptoms. However, the Delta and Gamma VOCs were associated with more severe cases.

2. Risk Factors for Severe Disease: Throughout the pandemic, diabetes and obesity consistently emerged as risk factors for severe disease in young patients.

3. Risk of Infection: The risk of contracting a SARS-CoV-2 VOC appeared to increase with age, indicating the importance of age-related factors in infection susceptibility.

4. Risk of Transmission: Intriguingly, daycare settings showed that the risk of onward transmission of VOCs was higher among younger children compared to older children or partially vaccinated adults. These findings underscore the significance of targeting transmission prevention in specific age groups.

5. Long-Term Consequences: Long-term symptoms following an infection with a VOC were relatively rare, affecting less than 5% of children and adolescents.

Overall, the study suggests that the patterns of SARS-CoV-2 VOC infections in children and adolescents closely mirror those of earlier viral lineages. However, the researchers emphasize the need for more refined comparisons between different pandemic periods, countries, and age groups. This should be coupled with comprehensive reporting of relevant contextual factors, including VOC prevalence, vaccination status of study participants, and the population's risk of exposure to SARS-CoV-2.

Ref: Wiedenmann M, Ipekci AM, Araujo-Chaveron L, et alSARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic reviewBMJ Open 2023;13:e072280. doi: 10.1136/bmjopen-2023-072280

Revolutionizing Prenatal Care: AI-Assisted Detection of Fetal Intracranial Malformations

In the realm of prenatal care, groundbreaking technology has emerged to transform the detection of congenital malformations in the central nervous system. A recent three-way crossover randomized control trial unveils the remarkable potential of an innovative deep learning system known as the Prenatal Ultrasound Diagnosis Artificial Intelligence Conduct System (PAICS) in aiding the detection of fetal intracranial malformations from neurosonographic images.

This groundbreaking study represents a pivotal step in advancing prenatal diagnosis capabilities. A total of 709 fetal neurosonographic images and videos were assessed interactively by 36 sonologists with varying levels of expertise in three distinct reading modes:

Unassisted Mode: Sonologists evaluated the images without the assistance of PAICS.

Concurrent Mode: PAICS was employed at the outset of the assessment.

Second Mode: Sonologists conducted an initial unaided interpretation, followed by PAICS assistance.

The results are truly transformative. With the support of PAICS, sonologists witnessed a significant enhancement in their diagnostic accuracy:

Unassisted Mode: 73% accuracy.

Concurrent Mode: 80% accuracy

Second Mode: 82% accuracy

In summary, the Prenatal Ultrasound Diagnosis Artificial Intelligence Conduct System (PAICS) demonstrates immense promise in elevating sonologists' capabilities for detecting fetal intracranial malformations from neurosonographic data.

Ref: Lin, M., Zhou, Q., Lei, T. et al. Deep learning system improved detection efficacy of fetal intracranial malformations in a randomized controlled trial. npj Digit. Med. 6, 191 (2023). https://doi.org/10.1038/s41746-023-00932-6

New Combination Therapy Improves Overall Survival in Relapsed Lung Cancer

The addition of berzosertib to topotecan in relapsed small cell lung cancer did not improve progression-free survival but significantly enhanced overall survival, a recent phase 2 study published in JAMA Oncology has shown. The study, conducted between December 1, 2019, and December 31, 2022, involved 60 patients with small cell lung cancer or SCLC who had experienced relapse following one or more prior therapies.

The primary objective was to investigate whether the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor, berzosertib, to the chemotherapy drug topotecan could lead to improved clinical outcomes. Patients were randomly assigned to one of two groups. Group 1 received topotecan alone, administered intravenously at a dose of 1.25 mg/m² on days 1 through 5, while Group 2 received a combination of topotecan with berzosertib. Berzosertib was administered intravenously at a dose of 210 mg/m² on days 2 and 5.

The primary endpoint of the study was progression-free survival (PFS) in the intention-to-treat population. Secondary endpoints included overall survival (OS) in the overall population and within subgroups of patients with platinum-sensitive or platinum-resistant tumors.

After a median follow-up period of 21.3 months, the study's results revealed that there was no significant difference in PFS between the two treatment groups. However, the combination therapy demonstrated a noteworthy improvement in overall survival. Patients in Group 2, who received the combination treatment, experienced significantly longer overall survival compared to those in Group 1. Adverse event profiles were similar between the two groups.

Ref: Takahashi N, Hao Z, Villaruz LC, et al. Berzosertib Plus Topotecan vs Topotecan Alone in Patients With Relapsed Small Cell Lung Cancer: A Randomized Clinical Trial. JAMA Oncol. Published online October 12, 2023. doi:10.1001/jamaoncol.2023.4025

Ceftobiprole Effective in Treating Staphylococcus aureus Bacteremia

In a significant medical advancement, a promising cephalosporin known as ceftobiprole has demonstrated its efficacy in treating complicated Staphylococcus aureus bacteremia, including the challenging methicillin-resistant S. aureus. This breakthrough was achieved through a meticulous phase 3 double-blind, double-dummy, noninferiority trial.

A total of 390 patients were randomly assigned in a 1:1 ratio to receive either ceftobiprole or daptomycin, along with optional aztreonam as decided by the trial-site investigators. Ceftobiprole was administered at a dose of 500 mg intravenously every 6 hours for 8 days, followed by administration every 8 hours. Daptomycin was delivered at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours.

Of the 390 patients, 387 had confirmed S. aureus bacteremia and received either ceftobiprole or daptomycin. The findings revealed that ceftobiprole achieved an impressive overall treatment success rate of 69.8%, while daptomycin achieved 68.7%. These results indicate noninferiority between ceftobiprole and daptomycin, with a minimal adjusted difference of 2.0 percentage points.

These positive outcomes extended to key subgroups and secondary measures, such as mortality rates and the percentage of patients with microbiologic eradication. Adverse events were reported in 63.4% of those who received ceftobiprole and 59.1% who received daptomycin, with gastrointestinal adverse events, primarily mild nausea, being more frequent with ceftobiprole.

Ref: Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia

List of authors, Thomas L. Holland et al,October 12, 2023

N Engl J Med 2023; 389:1390-1401

DOI: 10.1056/NEJMoa2300220