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Background: Severe COVID-19 is less common in children than in adults. Increasing evidence show that distinct immune-pathological changes can persist weeks or months after SARS-CoV2 infection, leading to Long COVID (LC). We investigated the systemic type I/III interferon (IFN-I/III) and inflammation response in peripheral blood mononuclear cells (PBMCs) of children with and without LC symptoms. Method(s): Blood samples were collected from children attending Umberto I hospital of Rome, within 3-6 months after a SARS-CoV-2 positive test and from control children. RNA was extracted from PBMCs for determining the levels of IFN-I (IFN-Alpha2, -Beta, -Epsilon and -Omega), IFN-III (IFN-Lambda1-3), NLRP3 and IL-1beta genes, and miR-141 expression by quantitative RealTime-PCR assays, normalized to housekeeping GUS gene and RNU6B, respectively. Result(s): 28 participants (M 12.5y SD 3.0) with LC symptoms, 28 participants (M 11.8y SD 3.0) without LC symptoms and 18 children who've never had SARS-CoV- 2 infection (M 10.5y SD 3.1) were enrolled. Comparing the three study groups, we found reduced levels of IFN-Lambda1, IFN-Lambda2 and IFN-Lambda3 (p=0.006, p< 0.001, p=0.012, respectively;Kruskal-Wallis (KW) test) mRNA in patients who have had SARS-CoV-2 infection as opposed to control group, whereas transcript levels of IFN-Epsilon (p= 0.019;KW test) were increased in the former with respect to the latter group;as well, remaining IFN-I genes analyzed showed a tendency to be up-regulated. As far as NLRP3 and IL-1beta levels was concerned, these genes were increased in LC patients (p< 0.001 for both genes;KW test). Additionally, miR-141, which has been reported to regulate inflammasome response, was overexpressed in LC patients (p< 0.001;Mann-Whitney test). Conclusion(s): These results showed a decreased levels of IFN-III mRNAs and an overexpression of IFN-Epsilon in children after 3-6 months of SARS-CoV-2 infection regardless of development of LC symptoms, suggesting that SARSCoV- 2 could have caused dysregulation of IFN response through unknown mechanisms (e.g. epigenetic modifications). Also, we found an overexpression of miR-141, NLRP3 and IL-1beta mRNAs in LC patients, indicating that a prolonged activation of inflammasome pathways could be associated with the development of LC symptoms.
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Background: In the northern hemisphere, Respiratory Syncytial Virus (RSV) is more frequently detected from December to February. In Italy, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presented a peak in incidence from the end of December 2021 to February 2022. Aim(s): To evaluate how SARS-CoV-2 pandemic has influenced RSV circulation. Method(s): We evaluated 389 children, aged 0-18 years, admitted for respiratory tract infections from September 2021 to January 2022 throughout Italy, from the north to the south. Children underwent nasal washing from 1 to 3 days after hospitalization. A (RT)-PCR was developed for detecting 15 respiratory viruses, including RSV, influenza virus A and B, human coronavirus OC43, 229E, NL-63 and HUK1, adenovirus, rhinovirus, parainfluenza virus 1-3, human bocavirus and human metapneumovirus. Result(s): We detected a virus in 338 children (86.9%): RSV was found in 267 (68.7%), other viruses in 71 (18.3%). 51 children (13.1%) resulted negative. Dividing our observational period in two-week timeframes, we found that RSV showed an early peak from October to the first half of December 2021 compared to its usual seasonality. In a previous study, we have demonstrated that RSV circulation was incredibly low from September 2020 to January 2021, in contrast with what we found in the same period in 2021-2022. Comparing RSV and SARS-CoV-2 incidences, we found that these two viruses spread in opposite ways: when SARS-CoV-2 present an incidence peak, RSV circulation reduced and viceversa. Conclusion(s): The relationship between RSV and SARS-CoV-2 showed that viral interference plays a crucial role in their epidemiology.
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Introduction: Children infected with the severe acute respiratory coronavirus 2 (SARS-CoV-2) are mostly asymptomatic or mild symptomatic. Some children experience persistent symptoms after SARS-CoV-2 infection, which may be consistent with Long COVID. Aim(s): To assess the frequency of both acute and persisting Coronavirus disease (COVID-19) symptoms in children and to search for the presence of risk factors for acute or persisting COVID-19 symptoms. Method(s): We included 697 children, aged between 0 and 18 years, who had previous SARS CoV-2 infection. Children and parents were asked questions regarding symptoms in the acute phase of COVID-19 and also persistent symptoms (extending beyond or developing 30 days and 90 days after initial diagnosis). Result(s): 79,2% of children were symptomatic in the acute phase of COVID-19;the most common acute symptoms were fever (49,6%), cough (22,1%), headache (37,9%) and asthenia (25,8%). 26,8% of children reported symptoms 30 days after initial diagnosis and 10,2% of children presented symptoms 90 days after initial diagnosis;the most common reported symptom was asthenia respectively in 12,3% (after 30 days) and in 4,9% of children (after 90 days). Persisting symptoms after 30 days were mostly present in overweigh or obese girls (35,8% vs 64,2%, p-value 0,03) and in children with asthenia (41,3% vs 20,3, p-value 0,001) in the acute phase. Children with symptoms 90 days after initial diagnosis most frequently had asthenia in the acute phase. Conclusion(s): We confirm that SARS-CoV-2 infection in children is generally mild. Also children can experience persisting symptoms that are significantly more frequent if they have a symptomatic disease and asthenia.
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Background: Children generally develop asymptomatic or mild COVID-19 disease, despite the exact mechanisms that protect them from severity are yet to be defined. Since humoral response to SARS-CoV-2 infection in children is still poorly investigated, we aimed to analyze circulating levels of anti-Spike IgA and IgG in pediatric population up to 8 months after SARS-CoV-2 infection, to delineate whether COVID-19 outcomes could impact on antibody (Ab) levels. Methods: A total of 115 COVID-19 young patients (mean age: 11.5 years, range 1-19 years) were enrolled between October 2020 and March 2021. All cases were confirmed SARS-CoV-2 infection by use of a diagnostic molecular assay on nasopharyngeal swabs. Circulating anti-SARS-CoV-2 IgG and IgA were measured using ELISA assays at one-month (T1), two-month (T2) and eight-month (T3) follow-up blood samples of young partecipants. Results: Longitudinal observation of COVID-19 children showed a decreased circulating level of IgA at T2 and T3 respectively compared to T1 (p<0.001). Persistent levels of anti-Spike IgG were observed at least two-month post infection but they significantly decreased at T3 (p<0.001). Stratifying children in two age-classes (1-9 and 10-19 years old) we found significantly higher levels of IgA in younger children at T1, T2 and T3 than in children older than 10 years old (p=0.012;p=0.041;p=0.036, respectively). Differently, younger children had a significantly higher level of IgG at T2 (p=0.029) and at T3 (p=0.049), but not at T1. Stratifying children based on the presence or absence of SARS-CoV-2 correlated symptoms or on the basis of underlying diseases, we did not observe differences in blood levels of IgA and IgG in all time points analyzed. Conclusion: Our longitudinal data indicated that younger children are characterized by an elevated peak of early IgA and are also defined by a robust induction of IgG, with respect to the older. These results contrast with what is common in SARS-CoV-2 infection in adults that elicit higher levels of polyfunctional Abs in severe disease. If confirmed in larger groups, these data would suggest that pediatric patients that usually have an efficient control of SARS-CoV-2 infections without inflammation would also elicit a humoral immune response protective from reinfections.