Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: A Scientific Statement From the American Heart Association

Circulation, Ahead of Print. Cardiac arrhythmias are commonly noted in patients during infections with and recovery from COVID-19. Arrhythmic manifestations span the spectrum of innocuous and benign to life-threatening and deadly. Various pathophysiological mechanisms have been proposed. Debate continues on the impact of incident and exacerbated arrhythmias on the acute and chronic (recovery) phase of the illness. COVID-19 and COVID-19 vaccine–associated myocardial inflammation and autonomic disruption remain concerns. As the pandemic has transformed to an endemic, with discovery of new SARS-CoV-2 variants, updated vaccines, and potent antiviral drugs, vigilance for COVID-19–associated arrhythmic and dysautonomic manifestations remains. The objective of this American Heart Association scientific statement is to review the available evidence on the epidemiology, pathophysiology, clinical presentation, and management of cardiac arrhythmias and autonomic dysfunction in patients infected with and recovering from COVID-19 and to provide evidence-based guidance. The writing committee’s consensus on implications for clinical practice, gaps in knowledge, and directions for future research are highlighted.

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Ottobre 2024

Decline in and recovery of fertility rates after COVID-19-related state of emergency in Japan

Introduction
The COVID-19 pandemic led to a decline in fertility rates worldwide. Although many regions have experienced a temporary drop in fertility rates with the spread of the infection, subsequent recovery has varied across countries. This study aimed to evaluate the impact of COVID-19 infection rates and regional sociodemographic factors on the recovery of fertility rates in Japan following the state of emergency.

Methods
This study examined prefectural fertility data from before the COVID-19 pandemic to forecast fertility rates up to 2022 using a seasonal autoregressive integrated moving average model. A regression analysis was conducted on fertility rates during the first state of emergency and the subsequent recovery rate with respect to the number of new COVID-19 cases and sociodemographic factors specific to each prefecture.

Results
During the first state of emergency, the monthly fertility rate decreased by an average of –13.8% (SD: 6.26, min: –28.78, max: 0.15) compared with the previous year. Over the following 22 months, the average fertility recovery rate was +2.31% (SD: 3.57; min: –8.55, max: 19.54). Multivariate analysis of the impact of the pandemic on fertility changes during the first emergency indicated a negative correlation between new COVID-19 cases per capita and the proportion of nuclear households. No significant correlation was found between fertility recovery rate and new COVID-19 cases or emergency duration. When classifying fertility rate fluctuation patterns before and after the emergency into four clusters, variations were noted in the proportion of the elderly population, marriage divorce rate and the number of internet searches related to pregnancy intentions across the clusters.

Conclusions
No association was found between pregnancy intentions related to the spread of infection, such as the number of new cases and the fertility recovery rate following the first state of emergency. Differences in the patterns of decline and recovery during the pandemic were observed based on population composition and internet searches for infection and pregnancy across different prefectures.

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Ottobre 2024

Assessing the safety and pharmacokinetics of casirivimab and imdevimab (CAS+IMD) in a cohort of pregnant outpatients with COVID-19: results from an adaptive, multicentre, randomised, double-blind, phase 1/2/3 study

Objective
Pregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women.

Methods
A phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age.

Results
In pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19–related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low.

Conclusion
CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age.

Trial registration number
NCT04425629.

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Ottobre 2024

Development and validation of predictive models for mortality of cases with COVID-19 (Omicron BA.5.2.48 and B.7.14): a retrospective study

Objectives
With the emergence of new COVID-19 variants (Omicron BA.5.2.48 and B.7.14), predicting the mortality of infected patients has become increasingly challenging due to the continuous mutation of the virus. Existing models have shown poor performance and limited clinical utility. This study aims to identify the independent risk factors and develop practical predictive models for mortality among patients infected with new COVID-19 variants.

Design
A retrospective study.

Setting and participants
We extracted data from 1029 COVID-19 patients in the respiratory disease wards of a general hospital in China between 22 December 2022 and 15 February 2023.

Outcome measures
Mortality within 15 days after hospital discharge.

Results
A total of 987 cases with new COVID-19 variants (Omicron BA.5.2.48 and B.7.14) were eventually included, among them, 153 (15.5%) died. Non-invasive ventilation, intubation, myoglobin, international normalised ratio, age, number of diagnoses, respiratory rate, pulse, neutrophil count and albumin were the most important predictors of mortality among new COVID-19 variants. The area under the curve of logistic regression (LR), decision tree (DT) and Extreme Gradient Boosting (XGBoost) models were 0.959, 0.883 and 0.993, respectively. The diagnostic accuracy was 0.926 for LR, 0.918 for DT and 0.977 for XGBoost. XGBoost model had the highest sensitivity (0.908) and specificity (0.989).

Conclusion
Our study developed and validated three practical models for predicting mortality in patients with new COVID-19 variants. All models performed well, and XGBoost was the best-performing model.

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Ottobre 2024

Uncovering Pediatric Long COVID

The COVID-19 pandemic has had devastating consequences globally, and the immediate and short-term consequences of SARS-CoV-2 infection have been well described. Although most individuals recover, many endure longer-lasting effects, referred to as long COVID, post-COVID condition, or postacute sequelae of SARS-CoV-2 (PASC). PASC is composed of a heterogeneous collection of symptoms and conditions that can affect virtually any organ system, with common manifestations including fatigue, cough, malaise, and pain. Those at increased risk for long COVID include females, those hospitalized due to acute COVID-19, and individuals with underlying comorbidities. Several hypotheses have been proposed to explain the underlying pathophysiology, which is likely multifactorial, including immune dysregulation, autoimmunity and immune printing, microvascular clotting with endothelial dysfunction, and impaired neurological signaling.

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Ottobre 2024