Replication properties and immunomodulatory effects of human cytomegalovirus infection impact the clinical presentation in congenital patients: A case series.

BACKGROUND: Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among newborns worldwide. Although both the host's and the virus' genetic backgrounds contribute to the outcome of infections, significant gaps remain in our understanding of the exact mechanisms that determine disease severity. OBJECTIVES: In this study, we sought to identify a correlation between the virological features of different HCMV strains with the clinical and pathological features of congenitally infected newborns, therefore proposing new possible prognostic factors. STUDY DESIGN: This short communication presents five newborns with congenital cytomegalovirus infection, whose clinical phenotype during fetal, neonatal, and follow-up periods is correlated with in-vitro growth properties, immunomodulatory abilities and genome variability of HCMV strains isolated from organic samples (urine) of the patients. RESULTS: The five patients described in this short communication displayed a heterogeneous clinical phenotype and different virus replication properties, immunomodulatory abilities, and genetic polymorphisms. Interestingly, we observed that an attenuate viral replication in-vitro influences the immunomodulatory abilities of HCMV, leading to more severe congenital infections and long-term sequelae. Conversely, infection with viruses characterized by aggressive replicative behavior in-vitro resulted in asymptomatic patients' phenotypes. CONCLUSIONS: Overall, this case series suggests the hypothesis that genetic variability and differences in the replicative behavior of HCMV strains result in clinical phenotypes of different severity, most likely due to different immunomodulatory properties of the virus.

Response to commentary 'long COVID-19/post-COVID condition in children: do we all speak the same language?

Here we present the Authors' answer to the Letter written by Dr. Garazzino and Colleagues with reference to our article "Long COVID-19 in children: an Italian cohort study".

Long COVID-19 in children: an Italian cohort study.

BACKGROUND: Long COVID-19 syndrome is a complex of symptoms that occurs after the acute SARS-CoV-2 infection, in the absence of other possible diagnoses. Studies on Long COVID-19 in pediatric population are scanty and heterogeneous in design, inclusion criteria, outcomes, and follow-up time. The objective of the present study is to assess the prevalence of Long COVID-19 syndrome in a cohort of Italian pediatric primary care patients, observed for a period of time of 8 to 36 weeks from healing. Prevalence was also assessed in a cohort of pediatric patients hospitalized during acute infection. METHODS: Data concerning 629 primary care patients with previous acute SARS-CoV-2 infection were collected by a questionnaire filled in by Primary Care Pediatrician (PCP). The questionnaire was administrated to patients by 18 PCPs based in 8 different Italian regions from June to August 2021. Data concerning 60 hospitalized patients were also collected by consultation of clinical documents. RESULTS: Cumulative incidence of Long COVID-19 resulted to be 24.3% in primary care patients and 58% in hospitalized patients. The most frequently reported symptoms were abnormal fatigue (7%), neurological (6.8%), and respiratory disorders (6%) for the primary care cohort. Hospitalized patients displayed more frequently psychological symptoms (36.7%), cardiac involvement (23.3%), and respiratory disorders (18.3%). No difference was observed in cumulative incidence in males and females in both cohorts. Previous diseases did not influence the probability to develop Long COVID-19. The prevalence of Long COVID-19 was 46.5% in children who were symptomatic during acute infection and 11.5% in asymptomatic ones. Children aged 0 to 5 years had a greater risk to develop respiratory symptoms, while adolescents (aged 11-16 years) had a greater risk to develop neurological and psychological Long COVID-19 symptoms. CONCLUSIONS: Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The results stress the importance of monitoring primary care pediatric patients after acute COVID-19 infection and the relevance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.