June 13, 2024

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RSV

Respiratory Syncytial Virus-Associated Hospitalizations in Children <5 Years: 2016–2022
Prospective surveillance for acute respiratory illness during 2016–2022 at seven pediatric hospitals. They estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 pre/-pandemic seasons (2016–2020) to those hospitalized in 2021 or 2022. RSV-associated hospitalization rates were higher in 2021 and 2022 than the pre-pandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37–2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in pre-pandemic seasons.
Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023–January 2024
In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), the authors estimated nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. They conducted a case–control study based on the test-negative design and included 288 infants reported by 20 PICUs. They estimated nirsevimab effectiveness at 75.9% (48.5–88.7) in the main analysis and 80.6% (61.6–90.3) and 80.4% (61.7–89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

COVID: Children and Other Vulnerable Populations

Neurodevelopmental Delay in Children Exposed to Maternal SARS-CoV-2 In-utero
Investigators assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19-exposed children between 5–30 months of age and 128 control children between 6–38 months of age. They found that children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls. We read that no participants in Rio were vaccinated before COVID-19, while 30.4% of LA women had received COVID-19 vaccination before infection. 8.8% of mothers in LA had severe COVID-19 versus 34.6% of mothers in Rio. In Rio, (12%) of the children were delayed in the COVID-19 cohort, as opposed to (2.6%) in the control group, p = 0.02. In LA, children (5.7%) were delayed as compared to none in the control group. Here we see that in a cohort with 30% vaccination versus 0% a difference in DD for the kids from 12% to 5.7%.
COVID-19 is Associated with Early Emergence of Preeclampsia: Results from a Large Regional Collaborative
A retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA, formed the study population. Of the N = 1,458 participants, 369 had SARS-CoV-2 infection (cases). Controls were uninfected pregnancies that were delivered in the same obstetric unit within 30 days of the index case. SARS-CoV-2 infection during pregnancy increased the risk of preeclampsia [adjusted aRR = 1.69 (1.26–2.26)], preeclampsia involving placental lesions [aRR = 1.97(1.14–3.4)] and preterm preeclampsia 2.48(1.48–4.17). Although the highest rate of preeclampsia was observed in patients infected with SARS-CoV-2 who were symptomatic (18.4%), there was increased risk even in asymptomatic SARS-CoV-2 infected patients (14.2%) relative to non-infected controls (8.7%) (p < 0.05). This association with symptomatology was also noted with preterm preeclampsia for which the rate doubled from 2.7% in controls to 5.2% in asymptomatic cases and reached 11.8% among symptomatic cases (p < 0.05).
Effectiveness of Nirmatrelvir/ritonavir in Children and Adolescents Aged 12–17 Years Following SARS-CoV-2 Omicron Infection: A Target Trial Emulation
In this study the primary outcome was 28 day all-cause mortality or all-cause hospitalization. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95% CI = 0.19%–0.31%; relative risk = 0.66, 95%CI = 0.56–0.71).

COVID: The Late Phase/PASC/Long COVID

Nirmatrelvir-Ritonavir and Symptoms in Adults with Postacute Sequelae of SARS-CoV-2 Infection The STOP-PASC Randomized Clinical Trial
Here is an investigation into Paxlovid as a therapeutic for Long COVID. These are the results of a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of three months or longer duration. Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days. Primary outcome was a pooled severity of six PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert Scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade. In short, there was no indication here that Paxlovid was an effective therapeutic for the treatment of Long COVID. The authors write: ”This trial’s results do not reject the hypothesis that viral persistence may lead to PASC but they will help inform further studies in this area. None of the participant baseline stool specimens had detectable SARS-CoV-2 RNA; other tissues were not assessed. As assays to detect SARS-CoV-2 reservoirs become optimized and validated, they could help to identify individuals who may benefit from antiviral therapy. Longer treatment durations, dose variations, optimal timing, and different phenotypes of PASC should be investigated in larger studies.”