ABSTRACT
Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.
Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Endogenous Retroviruses/metabolism , SARS-CoV-2/isolation & purification , Severity of Illness Index , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Child , Endogenous Retroviruses/genetics , Female , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Humans , Interferon Type I/genetics , Interferon Type I/metabolism , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interferons/genetics , Interferons/metabolism , Italy/epidemiology , Male , Tripartite Motif-Containing Protein 28/genetics , Tripartite Motif-Containing Protein 28/metabolism , Interferon LambdaABSTRACT
BACKGROUND: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. OBJECTIVES: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. METHODS: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. RESULTS: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. CONCLUSIONS: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation/drug effects , COVID-19 Drug Treatment , Thromboembolism/prevention & control , Adolescent , Age Factors , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , COVID-19/blood , COVID-19/complications , Child , Child, Preschool , Clinical Decision-Making , Female , Hospitalization , Humans , Infant , Infant, Newborn , Italy , Male , Prospective Studies , Risk Factors , Thromboembolism/blood , Thromboembolism/etiology , Time Factors , Treatment Outcome , Young AdultABSTRACT
Little is known about the sequelae of SARS-CoV-2 infection in children. In a COVID-19 dedicated clinic, we followed-up for 4 months 25 children previously hospitalized for COVID-19, performing clinical, laboratory, and lung ultrasound evaluation. Mid-term sequelae were rarely observed in our COVID-19 children's cohort.