Sudden cardiac arrest in infants and children: proposal for a diagnostic workup to identify the etiology. An 18-year multicenter evaluation in the Netherlands.

Sudden cardiac arrest (SCA) studies are often population-based, limited to sudden cardiac death, and excluding infants. To guide prevention opportunities, it is essential to be informed of pediatric SCA etiologies. Unfortunately, etiologies frequently remain unresolved. The objectives of this study were to determine paediatric SCA etiology, and to evaluate the extent of post-SCA investigations and to assess the performance of previous cardiac evaluation in detecting conditions predisposing to SCA. In a retrospective cohort (2002-2019), all children 0-18 years with out-of-hospital cardiac arrest (OHCA) referred to Erasmus MC Sophia Children's Hospital or the Amsterdam UMC (tertiary-care university hospitals), with cardiac or unresolved etiologies were eligible for inclusion. SCA etiologies, cardiac and family history and etiologic investigations in unresolved cases were assessed. The etiology of arrest could be determined in 52% of 172 cases. Predominant etiologies in children ≥ 1 year (n = 99) were primary arrhythmogenic disorders (34%), cardiomyopathies (22%) and unresolved (32%). Events in children < 1 year (n = 73) were largely unresolved (70%) or caused by cardiomyopathy (8%), congenital heart anomaly (8%) or myocarditis (7%). Of 83 children with unresolved etiology a family history was performed in 51%, an autopsy in 51% and genetic testing in 15%. Pre-existing cardiac conditions presumably causative for SCA were diagnosed in 9%, and remained unrecognized despite prior evaluation in 13%. CONCLUSION: SCA etiology remained unresolved in 83 of 172 cases (48%) and essential diagnostic investigations were often not performed. Over one-fifth of SCA patients underwent prior cardiac evaluation, which did not lead to recognition of a cardiac condition predisposing to SCA in all of them. The diagnostic post-SCA approach should be improved and the proposed standardized pediatric post-SCA diagnostics protocol may ensure a consistent and systematic evaluation process increasing the diagnostic yield. WHAT IS KNOWN: • Arrests in infants remain unresolved in most cases. In children > 1 year, predominant etiologies are primary arrhythmia disorders, cardiomyopathy and myocarditis. • Studies investigating sudden cardiac arrest are often limited to sudden cardiac death (SCD) in 1 to 40 year old persons, excluding infants and successfully resuscitated children. WHAT IS NEW: • In patients with unresolved SCA events, the diagnostic work up was often incompletely performed. • Over one fifth of victims had prior cardiac evaluation before the arrest, with either a diagnosed cardiac condition (9%) or an unrecognized cardiac condition (13%).

One-fourth of COVID-19 patients have an impaired pulmonary function after 12 months of disease onset.

BACKGROUND: There is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of pulmonary impairment across the full spectrum of COVID-19 severity over time. METHODS: In a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression. FINDINGS: Between May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (p<0·001) and initial severe/critical disease (p<0·001) were associated with slower improvement of pulmonary function over time, adjusted for age and sex. HRQL improved over time and at 12 months was comparable to individuals without impaired pulmonary function. INTERPRETATION: The prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities.

Cross-reactive antibodies after SARS-CoV-2 infection and vaccination.

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.